Document KGnd54vpeprX9jxj4yy2Exvjw

r*.eonntea sr-n A^erica-v I.nocstsi^i, ilrctt^E .UsoCMTio* Jochnii VoL _', Xo. i __ Ci^scer, .j51 C^Pl'Ti^Qt v) 1061 by . *.s rentes m Jc ^kiiisCo. The Toxicity of Vinyl Chloride as Determined by Repeated Exposure of Laboratory Animals T. R. TORKELSON. M.S.. F. OYEN. and V. K. ROWE, M.S. 3iocr.em.icai Research, Laboratory. The Dow Chemical Company, Midland. Michigan Groups of laboratory animals were exposed repeatedly for up to six months to either 00. 200, 100 or 50 ppm vinyi chloride in air. Detectable changes occurred at ail but the lowest concentration. The results are discussed and handling precautions suggested. introduction INYL chloride (CEt=CEC1) a a chemical of great industrial importance. It is used :n the preparation of poiy-unyi chloride resin, as a copolymer in saran and other piasr.cs, as a chemical intermediate and as a solvent. Be cause of the flammability of vinyi chior.de, it has been generally assumed that the greatest hazard associated with vinyi chioride is that due to its flammability rather than its toxicity.1 The toxicity of vinyi chioride has been re viewed by von Oettingen1 and more recently by Mastromatteo et al.s von Oettmgsn concluded that the gas was anesthetic in high concentra tions and that considerable interest had been shown in the use of vinyi chioride as a surgical anesthetic. However, its erect on the circulatory system has discouraged exploitation of this prop erty. No doubt the hazard from flammability has aiso hindered this use. Oniy limited repeated exposures which were reported by Schaumann" were discussed by von Oettmgen. These repeated exposures indicated little or no chronic erects even from anesthetic concentrations. Mastromatteo et at.3 ziso discussed the pub lished data and reported the resuits of single exposures of mice, rats and guinea nigs which confirmed the low acute toxicity of vinyi chioride. Mastromatteo reported that oniy two human fatalities due to vmyi chloride had been reported. It can be concluded from the published toxicoiosic.nl data that anesthesia is the oniy sig nificant effect of acute exposure. Sufficient re peated exnosurcs have not been reported to draw conclusions about chronic toxicitv. The Threshoiu Limit Value of 300 ppm suggested by the American Conference of Governmental In dustrial Hvaienists (ACGIHi* is reported by Smvrh' to be based on single animal exposures and human experience. The following report summarizes the results of repeated exposures of laboratory animals to either 500, 200, 100 or 30 ppm of vinyi chior.de. The significance of the resuits is discussed ana recommendations for a threshold limit vaiue are made. Experimental Procedures Materials Tested Vinyi chloride, CHr=CHCl, is a colorless gas. I; has a boiling point of -- 13.35'C (-r"-93"F) and a freezing point of --154*C (--244.S2*F). The material poiymerizes readily and hence is sometimes inhibited with phenol or tertiary butyicatechol. Vinyi chloride is very fiammabie, its flashpoint being --73"C ( -- 10S"F). The ex plosive limits are from 4% to 22% by volume.It has little odor although high concentrations may smeil faintly sweet. A single, uninhibited sample was used in these studies. It was shown by mass spectrograpmc analysis to be essentially pure CH,=CECI. air being the oniy impurity detected in gas phase samples. Source and Feeding of Animals The rats ana rabbits used in this study were obtained from the stock colony of this labora tory, the guinea pigs were obtained from a commercial grower and the dogs were purebred beagies obtained from a local kennel. The rats and dogs were fed Purina Laboratory Chow1 or Famo Laboratory Ration.3 The rabbits and guinea pics received Famo Rabbit Breeder Ration. The guinea pig diet was supplemented with carrots. Experimental Protocol The experiments were conducted in three phases. In the first phase, groups of 10 maic R&SI 62675 Industrial Hygiene Journal and 10 f-smaie rats were exposed seven hours per cay eve days per week to 500 ppm for 4.5 months. Exposures were given in a 150-liter chamber previously described,"0 Mortaiity ana growth recorcs were kept. Final organ weignts vers obtained and tissues were saved for micro scopic examination. Five mate ana eve femme rats servea as unexposed controis. The second phase consisted of repeated 7hour daily exposures of 20-24 maie and 24 fe male rats, ten maie ana eignt femaie guinea pigs, three mme and three femaie rabbits and one maie and one femaie dog to either 200 ppm or 100 ppm 01 vinyi chloride. These animals and two groups of controis were caretuiiy selectee and matched on the basis of age, contrition and weight. The first group of controis received no exposure and served as unexposed controis. The second groun received repeated daily 7heur exnosures to room air in a chamber similar to the one used for exposures to the chemical. This group is referred to as the air-exposed con trol group. In addition to the animals receiving 7-hour daiiy exposures, eight separate groups of five maie rats each were excused to either 220 or 100 ppm for 4. 2, 1 or 0.5 hours per day. The procedures and eaupiment used were bas ically the same as reported previously." Growth and mortaiity records were kept on ail groups. The livers of the dogs were biopsied prior to ex posure and after 3Vg months of exposure, hence the liver of each dog served as its own control. Pre-exposure and terminal hematological deter minations were made on ail dogs and terminal determinations on representative groups of rats. Urine samples were coiiected from the dogs and representative groups of rats. At the termination of the experiment, pan of the rats were starved overnight and then these and ail the guinea pigs and rabbits were killed by decapitation on the day after their last exposure. The doss were killed by exsanguination after anesthesia with thiopentai. sodium (Per.tothal. Abbott). Samcies of blood were taken of representative groups of animals for determination of alkaline pnosnhatase. serum-urea-nitrogen (SUNG, serum-giutamic-pyruvic-transaminase (SGPT). and serum-giutamic-oxalacetic-transaminase 'SGOT1. The organs were weighed and tissues fixed for histopathoiogical examination. The rats which were not killed the day after exposures were stopped were pastured for eight weeks and then sacrificed in the previously described manner. 1 ,ie third phase of this experiment consisted of repeated daily 7-hour exposures of 21 male and 24 female rats, 12 male and 12 femaie guinea pigs, 3 maie and 3 female rabbits and one maie and one femaie dog to 50 ppm vinyl chloride. Equai matched groups served os unexposed ana. air-exposed controls. Three additional groups of 10 maie rats each were exposed for 4. 2 or 1 hour per cav to 50 ppm. The procedures followed were essentially the same as used for exposures to 200 and 100 ppm except that hematological examinations were made on the dogs after three months and liver biopsies were made only prior to exposure. Urine was collected from the rabbits as well as the rats and dogs. The rats which were not sacrificed at the end of the exposures were pastured for six weeks and then sacrificed. Equipment Used The exposure equipment used has been de scribed previously." However, in order to gain additional data about the results of repeated short daily exposures, it was necessary to devise a method of introducing additional groups of rats. This was done without opening the doors of the chamber by dropping the rats through chutes made of 3.25-inch stainless steel tubing. These chutes were closed with a rubber stopper except during the brief time it took to insert the rats. The chutes, which were sioped at a 45' an gle, ended in covered, screened cages inside the chamber. The additional groups were started 3, 5. 6 and 6.5 hours after the 7-hour exposures started. Since ail animals were removed after the 7-hour exposure was completed, this routine re suited in exposures lasting 4, 2, 1 or 0.5 hours. The vinyi chloride was metered from a saran plastic bag which served as a reservoir for the gas. Metering of the gas was done by Dual Syringe Pumps."3 Total air flow through the chambers was measured by means of calibrated flow meters. Analysis oj the Chamber Atmospheres Analyses of the air were made by direct com bustion of a known volume of air in a heated quart: tube. The resulting chloride was trapped in IGj sodium formate--1% sodium carbonate solution and subsequently titrated by a microVoihard technique. The results of the individual analvses were within 157o of the theoretical con centrations during the exposures to 200, 100 and 50 ppm. The average concentrations recovered 'ere 107, 100.5 and 4S.7 ppm respectively. Results of Repeated Exposures Exposure to S00 ppm Vinyl Chloride The rats exposed repeatedly at 500 ppm for 4 5 monrhs, grew normally and no changes were R&S162676 October, 1361 ITable Summary of Terminal Average Body ana Organ Weights of Male P.ats Receiving P.epeated Exposures to Vinyi Chloride 5 Davs oer Week Concentration in ppm Mancha on Exposure Euratton at Cany Exposure, uOur5 Ratio of Survival ?;nai Aver aee floay We:*nt, S ; Lun? Orsjan We "--3. ;/ ICO 5 3ccy Wei;st Heart Liver aJinev Spleen i Testes Viesposea control .... 00 0 4.5 0 ; Viexpoaea control............ Air eipcaea control........... 220 ::o 220 220 220 120 100 ::a 120 100 ^.`nexpoaea* control.......... .\*r expotea* control......... .; 220* ' 100* 0 5 o a 8 3 0 7 4 2 1 0.5 7 4 2 1 0.5 0 7 * Pastured lor 8 \tmks alter exposures ceased. (a) P - 0.001 (b) P - <0.001 'oi p - o.o; (d) P - 0.1 (e) P - 0.03 '0 P - 0.10 1/5 ;/io 11/12 10/12 9/12 4/5 4/5 g/5 4/5 7/12 3/5 4/5 3/5 5/5 10/12 a/12 3/3 5/7 304 : 0.54 0.33 312 i 0.23 0.33 3.33 : 0.71 * ! 0.73 0.15 0.17 0.39 0.95 243 0.33 0.22 :.-:5 , 0.59 0.14 0.50 336 i -i2 0.32 . ::: : o.;o 0.15 0.76 341 j 0.52 0.32 ' 2 55' . 0.53 0.17 0.04 243 : 0.47 0.20 . 2.23= 1 0.54 0.16 0.25 241 0.55 0.20 ' n - 0.54 o.ia 0.29 250 ' 9,43 0.25 2.45 0.51 0.13 0.73 333 0.51 0.20 r 2.33 0.57 0.14 0.95 252 0.51 0.33 0.53 0.15 0.35 36Q 0.51 0.03 2.52 0.55 0.15 9.74 231 , 0.53 0.:; * -14 0.57 0.16 9.93 337 - 0.43 o.:s t** , 0.64 0.15 0.73 353 0.45 0.30 ' A . r} ] 0.64 0.16 0.73 234 0.49 0.51 ; *^ T^v | 0.64 0.14 0.34 533 j 0.53 o.;o ` m, 4 1 j 0.63 0.15 0.73 | 335 | 0.47 378 l: 0.47 0.113 ' 8 f " j 0.64 0.31 i rt (* { j 0.55 0.15 0.14 0.71 0.75 apparent grossly at autopsy. Microscopically taeir iivers showed increased central lobular granular degeneration and the kidneys showed interstitial and tabular changes. The average weight increase of the livers of the maie rats was statistically sigmricant (P = 0.001), Table I. The average weight of the livers of the female rats was above that of the controls but not statis tically significant. Table II. SUN, SGPT, SGOT. and alkaline phosphatase determinations were within normal iimits (Table III). Exposure to -DO ppm Vinyi Chloride All groups exposed seven hours per day ICS44 times in 204 days were normal in anpearance, mortaiitv and growth. Hematoiogicai. SUN, SGOT. SGPT ana eikaiine phosphatase values iTable III) and the results of the unnalysis ere within normal limits. Gross pathology as normal in ail species. Micropathoiogy was normal in the rats, guinea pigs and dogs, howI'ver. adverse enacts were noted in the livers of rabbits of both sexes. In the maie rabbits this was characterised by central lobuiar granular de generation and necrosis with some foamy vacuolation. In the female rabbits the changes noted were central lobuiar grammar degeneration and necrosis with penportai cetiuiar innitration. All organ weights were normal except for the livers of the maie and female rats which were in creased significantly after repeated daiiy 7hour exposures (Tables I. II, IV, V, VI, and VII), In the maies this increase was still appar ent eight weeks after exposure ceased, although the iiver weights appeared to be decreasing and returning to normai. The maie rats exposed to 200 ppm of vinyi chloride for either four or two hours per day for six months had elevated average liver weights (Table I). However, the small size of the ex perimental groups made the rinding statistically insignificant iP = 0.07 and 0.1). Tile groups ex posed for either 1 or 0.5 hours per day were en tirely normai. o ct- Industrial Hygiene Journal T.'.aLs II Summary of A'/erase Bony and Organ tVeights or Femaie Rat.- Reviving Reneiten 7-Hour Hxposures to Vir.yi Chloride 5 Days per Week !r ,j b-- Gr: .n Wei zzts. :o ? z oov 'z V- >e:?n t - - _ - _ *>'* *I*n 1- I: !" 7 r : - - ~-- - r L'zsizasca ccc* "'SI ......... Q 500 4.5 .' 5 .34 0-i2 0,41. : :e 0.0 I.:; 3/10 125 0.5310.SSI 4 4Atl 0.31 0.20 Uzexoofled coo* -31.................. 0 .2, 12 222 0,55 o.:s: * 0.52 i :: Air "icosea cnniroi $ ::o 5 ::-o i ' '.2' 222 0 55(0 20 : 0 il = 223 0 =:'0 33' - - -5. 0 ;1 . 1,12 221 Q.35'0.33i : as5 0.73 :,:o U2eI^)0aea, ccatroi.......... 0 3 j i11 Sn* 0-51 0.37; 2.37 ! 0 53 'j. Ii Air -xooa^o* control ......... 5 ::o* ;:q` Coexpoaeo coo"51.................. 5 6 0 Air eiooMQ control......... :o 5 Unexsoaeo** control............ 0 Air exooaea control*"....... 6 y\y. 2;a ,0,35:0.27; 2.1*7 0.52 ' ** 223 o.ui:a.;s: 3.23 * 0.51 : ;a * * '1 225 0.3310-401 0.53 j-2! 1! 2U 0-53.0,301 3.22 0.53 : :o j ! 1! 12/12! IQ*! 0-5310.331 :.53 ; 0.S4 2.22 226 0-5i:0.::' i 0.54 3.20 1 11/12! 125 0,6610,401 2.33 i 0.31 0 ; !ii i -V12: 221 0.0510.401 2.31 ; 0.37 0 13 50** 6 .2b 0.0510.23! 2.53 i O.S2u o :o 1 '.'.aturea ior 3 weexs aucr exposures cejiseu, *" Pajturoa for 6 weeks mwr exposures ceasea, P = o :: Oil P *- 0,03 (cj P ^ 0 01 'u! P * 0 05 /t-no.-iurc to 100 ppm Vinyl Chioride Ail species exposed to 100 ppm of vinvi chlo rine, seven hours per dny, ICS-144 times in 004 "'ere judged normal on the basis of the fol lowing criteria: anpoarance, mortality, growrn, nemntoiogical examination, SUN, SGOT, SGPT. aikaiine phosphatase determination, urinaivjis and gross and microscopic examination of Muiie. However, siigat increases were found in the average '.'/eights of the livers of maie and :emaie rats (Tobies I and II). Although not sig nificant statistically, an increase was aiso seen in the average weight of the livers of the maie rats exposed to 100 ppm for either four or two hours per day. The groups exposed for either 1.0 or 0.5 hour per day were entirely normal. Exposures to 50 ppm Vinyl Chloride The increase in weight of the rat Livers, the cruy sigruheam rinding :n animals exposed to ICO ppm. aid not occur m rats exposed reneateoiy to 50 ppm of vinyi chionde, ICO times m 139 days. Ail groups of animals were judged normal in ail otner respects. See Tables II. V, VI, VII. VIII and ITC. A. statistically significant decrease m Sidney weight which was seen m the femaie rats 'Tabie Hi was considered to be an artifact since it was not seen at rustier concentrations. Discussion H.epeateu exposure to vmyl chionde at con centrations considerably below the level that has been considered safe tor human exposure has been shown to have an effect on the liver and kidney of laboratory animals. Eistopathoiosical enanges and increased liver weights in maie and female rats were noted after repeated exposure at 500 ppm. Repeated exposure at 200 ppm for six months resuited in an increase in the average weigh: of the livers of male and femaie rats and micro pathological changes in the livers of the male and femnie rabbits. The only effect noted, after repeated daily 7-hour exposures to 1G0 ppm for six months was a slight increase in the aver age weight of the rat livers. Repeated 7-hour exposures to 50 ppm for six months had no enec: on any species studied. Hence, the highest con centration without detectable effect on any spe cies was 50 ppm. It is interesting to speculate on tiie apparent discrepancy between the etfects observed at LUO ppm in this experiment and the lack of reported injury in humans using a threshold limit of 500 ppm. Several factors may be contributory. First, the eifects noted in animals at 500 ppm were ouiv slight to moderate; growth, mortality, and gen eral appearance were unaifecied. Hence, it is possible that if humans were exposed repeatedly at 500 ppm siigiit injury might occur but due to tiie lack of subjective symptoms tiie injury would escape detection. Secondly, the injury* was apparently reversible. The liver weights of both male and femaie rars which had shown dennite increases after exposures at 200 and 100 ppm were normal or anproachinn normal after b-S weeks of recovery (Tables I. II anil VIII). Table III of Average Biochemical Values Determined tor Animals Receiving Repeated Esnosnres to V'mvi Clnonoe 5 Davs per IVeek Species ana Deg Xo. 5 Concentration in opts icntr.s 03 xnosure Duration , 05 *jidv Etaosurc 1 acurs Xcmocr j[ Ammais . ; .-.arose Biooa Urea Niirocrr.. rag/ AO rat 3GPT ' SCOT iigtru F ranxei Vans ait Ld? % 101........................... LI L'nespcseu control 0 v 113 .......................... Air exaciea control 3 <41............................... ::o 3 < VS ::o 3 0i ^ 1 IS 43 4 , 1 13 12 17 l. 3 11 IS 13 ' ts * 19 Oog * 1C5 , ,. % 107............................. * 1Q3 ........................... *i:o.................... ? Unespcseo control Air exposed control ::o ::o 0 3 3 j Rut...................................... m Unexcosen control ;:o o ::a "3 ;:a ::o ::o pjt............................. F L'nexnosec control "0 ::o ::o ?_tb'oit.................................... M Control ::o ::o 0 4-5 3 3 0 a 3 0 3 5 3 G 3 G Rabbit..............,............ . r Control ICO ::o j 5 3 3 i. 7 7; 7 ".3 i 5. 3 3: 7 4 ! 15.9 7 ; 17-7 4 4 '.l.i ; 5 7 t .- i 4 ; *4 7 : 0i 4; 7 i ; i. i 7 5 j lZ.5 3 ;.i 0 5 j 4,3 7 ' : i i7 2 i ti 1 0i 4.3 7 i - 1 3-3 j i 4,3 U 33 14 10 20.5* 13.3 13-3 13.2 17.7 15 0 13.3 15 2 20, o 22.C 22.2 --3 25 -i :s 33 :: :s 10 < 23 H 17 1*3 1 23 10 i u :o os ; 05 02 42 ! 07 oa 00 03 23 21 1 en 08 *2 23 ; :s 1 OS OS 1 * Because oi two unusually tuga inuividuai vaiuca in this zrouu these average values arc eievaieu ana do not corresponu with the values obtained on ainuuir control groups io our laboratory. Xormai control values are in the same ranges as those of the experimental groups listeu in tnu tuoie. Species or Dot; .* Table IV nummary of Averace Hematoio r'.eal Values ior Animals Receiving Repeated 7-Hour Exposures to Vinyi Chloride Moruns i S" .Concentration m =pm ! : menc I Ilcmo- ;loo.n Hemaiocnt WBC lu X Neutro-' pads i a; UJU i, , Lym pho cytes Mono- -Eosino* cytes i pniis Hat...................... Rat ., -................ ....... Rut........................ ....: Rut ...................... . , ; Dog *101 ....... .... Dog * 101 ......... ,. : Dog * 113 .i Dug *113 ., Dog * ill Dog * 111 ., ,; Dog * 'J*4 ... , Dog * VS . Dog < lud ,. Dog * lUti |Dog * 107 ... , ! Dog * 107 ! Dog * 103 . .. Dog * 103 ,,.,: Dog *110. i i , 1 Dog *110 ; M M f F M m :.i M :,i h M M F F F F F F F f Air expuaeu control 1 :oo Air exposed control i 200 Unexposeii coatroi 1 Unexposcu control 1 Air exposed control Air exposed control i '.'CU ::> j 100 too Uuexposed control ' L'nexposed control i Air exposeu control Air expiMen control ! :oo PJ0 :uj ;on 3 j r, d 0 3 0 0 0 'j J 3 0 *J 1) lj I) 3 .) G 4 14 5 5 1 14.4 51 50 15.3 20,5 71.2 1G.7 \'J 77.3 1.5 0,2 0.3 3 4 ; 14.0 49 5 13.5 IPS a 4.5 0.2 2.S S | 13.3 47.4 12.3 21.3 70.2 1 1-- -- -- -- _ 1.0 -s 4 1 ! IS S3 14.2 40 51 0 3 1 '4,5 0 13,5 ]1 23 5 U 1 14,5 s< 2 13 2 55 34 4 4 1 n 47 10 3 .5 23 3 13 I la h S3 15,5 30 41 : l ; 5-0 52 !'i 5 -0 40 4 4 t i io 54 13 ij jl 39 I) 0 1 14.5 01 21.3 42 37 3 IS l ! 15 5 54 16 5 51 41 1 i 1 i 15 1 ! io I j 14 I J 16 : !0 3 i 15 5 53 57 Si) 54 44 54 14.4 55 11.7 -jo 17,5 44 17,3 iO 10 J a 14 1 u US S3 48 51 ;o 4 3 0 2 1 j * 5 3 0 0 Industrial Hygiene Journal Z.-.2LZ V summary of Terminal Average 5ouv ar.d Organ Weigh:: of Guinea Pigs Receiving R.eneate'; Daily 7-Hour Exposures to Vinyi Ckiorice 5 Day= oer Week; for d Montr.s Table VII Summary of Final Body and Organ Weights of Dogs Receiving Repeated Daily 7-Hour Ex posures to Vinyl Chloride 5 Days per Week for 6 .Months M 1 L'zexpcsea i 3/:C: *,1- 3 ii 0.2S: 3.22 3.73 0.1C.3. ccntrci 1 :.i i *Ur exposeut 577~ :G20 9.52 r~ z':i 3.51 0,IQ 0 control ; M t 220 1 7::r 1044 ` 9.33 0.271 : :: 0 -:0,Q.02 0 M 1 ::o 7,'13 1QS9 1 0.52 Q e ** "*1 9.55'Q.U 9. M ! L'oexoosed j */:: :is : 0.50 0,22' 2.21 0 H 0.12 3. control M : Air exposed : ' 1: c 2i 0.27' 2.21 3.34 0,12.9 control M i 5j ia/12 1301 ., 9.5: 0.23: 2.:i 0 51 0-12:0- T ; Uneipcsea COQtTCl F ; Air excosea 1 5,5 :/3 :9 9 32 o,27` ::: ),3.0.12. =57:: 0,55 q *c; ^ 0.57'Q.H: control i F - i 7/3 ;97 1 0.74Q 0.27: 2.;oc 9.56 0,12; F ! ::o ! 7/S 949 i! 0.55 0 26! 2.53 0 lb O F i Uncxposed | 9/i2' 723 ;i 0.73 0.31. 3-41 0.55 0.13. control | Fi: -Air exposed i 3/12- 534 !1 0.55 0.251 3.54 0.55.0.I41 control 1 F i 13 11/12* 906 :1 0.69 0.23: 3.44 0.54:0.14: -aj ? * '>.05 fb) ? - o.:i (cj P - 0.2: Table VI Summary of Terminal Average Body and Organ Weights of Rabbits Receiving Reseated Daily 7-Eour Exposures to Vinyl Chlorine o Days per Week for d Months Or^an Weicnts. s/100 z 5oay \Veu5a1 3 z ; 1 i Orpan Weicr.ts. 5/100 ? s-- 3oay - x i: 3 - c*--- t ~ "f a i " I ij 1 'j ~Ji\ M :gi Unexposea 1/11 13,0 0,66:0.62::.46 0.:3'0,:2 0.15 control 1 !;1: :i 113 .Air exposed 1/11 3.5 0.63,0.77:2.53.0.47 0.19,0.14 control i !I', ; 91 111 200 1/1! 10.2 1.03 0.36:2.50 0.52,0.23 0.13 21 93 100 1/1! 12.0 0.35,0.5012.50 0.42 0.22 0.15 > * Unexposea 1/11 13.2 Q.30`0.73:2.50,0.52.0.22.0.11 controi 1 i1 -U. 156 .Ur exposed 1/11 10.6 0.77:0.37:3.05 0.45,0.35:0.14 M 152 control 50 1 l!-' 1/1! 9.5 0.S90.7S'2.40 0.45 0.22'0.12 V 136 Uaexoosea 1/11 9.5 0.71 0,6Si2-d7'0,43:0.2i: control 1 i11:1 * 107 Air exposed i/u 3.: '0.77:0.3013.15:0.43,0.32! control 1 iI11 F 103 200 i/ii 10.5 0.73:0. Till. 33:0.45,0.23! c no 100 i/u 11*3 0.9910.73:2.14:0.43:0.311 F 151 Unexposed 1/11 3*6 0.59:0.S2:4*10-0*45:O.43l control 1 1111ii r 155 Air exposed 1/11 11.3 .0,7010.3413*3110.40,0.251 control 1 iii!ii -r 161 50 1/11 7*4 o.57;o.7Si:.4s.o.47;o.33ii Table VIII Summary of Terminal Average Body and Organ Weights of Male Rats Receiving Repeated Ex posures to Vinyl Chloride 5 Days per Week i }iJs* o5 i1 Orsan Weights* ;t/l00g Body Weignt S** -|;1 S2 3=!! -s v"ji; 2 ?I.! . ! ?! 5 -* M 1 Unexpaaed ` 3.3 ; 3,ci 0.29*0.2:27 :).43:0.03 0 M | An exposed I 2 Z : 3.20 0.31.0.15,2,,i 0.4G 0.02 0 :i control M 220 M :oo M i UnexDosed | control | Z `3 1 3.43 0.32 0,19 2.24 0.5410.02 0,15 i 3/3 13.05 0.33.0.15 2.5J 0.49-0.02'0.:5 J 2 3 i 3.SU 0,22:0,17.2-33:0.45 0 02'0.;5 1 M ! Air exposed I 1.3 i 3.ST O.o;;n,:3 :.;s 0,53:0.o;i,a ; control M | :o F j I'ncxposetl 1 ; 3.2 ! 3.70 0 3C.O.:0 :.iij 0,47,0.03 0.17 2.2 4.13 0.31 0 17 2.23 0 40 0-031 * Ur -vuoaed I 1-3 j 3.01 0,30:0. IS 2.15 0,41 0.011 { F ri control ..'0 1 :i : : : 4.10 0.32:0.10-2.22 0 i2:o,05i , 2 7 1 4.12 0-2`JlO. IS`1 379.2SO.Q5i F | L'nexooscd { 3.3 i 4,31 0.30.0.171, 0 40:0.011 j control I ! Ii F 1 Air *xpoae<i i 2, 2 . 3.05 0 31) 0 17 1.23 0.39 0.011 ; control F 3.2 4.31 0 22 9 17 2. 10 0 23 U 01 Unexposea control 00 3/3 319 ,0.3010.33:2.07,0.73 0*13 0.93 : Air exposed 6 12/12 317 '0,5110.32;:.41 0.70!0.1S!0.31 control 50 50 Mill! 6 * 12/12 335 IQ.5010.3112.49,0.63:0.17:0.37 6 4 3/10 343 10.5110.33!2.59i0,6910* 1610*31 50 6 6/10 322 ;0.4'J:0.32!2.57:0*:0:U.10;0.30 50 8 1 9/10 343 .0.4710.32!:.51:0.73:0.1710.34 L'nexposed* 0 0 8/3 330 ,0.5310*3212.37:0.::.0.16:0.53 control Air exposed* a control ' 1i11:i 12/12 370 ,0.5310.2012.42:0.6410.14:0.75 {lliii 50* 6 7 l*Vlrt 300 ,0.49:0.33:2.31.0.55 0.15.0.32 III * Pastured for 0 weeks after exposures ceased. Thirdly, it is doubtful whether it would be possi ble for humans to be exposed continuously at 500 ppm in production plants since this high a gen eral concentration would indicate severe leaks in ; iu- equipment and extremely high concentrations ()<:iooer, 1061 W -- .`*^-3 TL*-, 1f-'V*.- Summary of Average Hematological Values for Dogs Receiving P.eneatea 7-Hour Exposures to Vinyi Chloride Got; Sex 'Morur.s ' Concentration ;n pfhi i t 00 1| , *m'--ene*t*' Xo. at Hemi- wbx x : Vrtro- L'.TTk 5 avl00 ; :ccr:: iC1 "pus - oo cytes loxo- Eqsiqo* cytes pnus Dm nr:..................... M ' Uoexpoaea control 1 Doc ' 153 ..................... it i Uaexpoaea control ! Doc ' 152 ................ It i Cneiposea coatrci Doc * 135................ . ; It j Air exposea control i Dec '156....................... :t ! .Ur exposea control Doc ' 153 .................... M ! Air exposea coctrei Do? '153..................... M i 55 Do? * 162................... .! it i 30 j Doc * 162..................... It i 3D ! Doc * 151..............- F i Unexposea control Doc ' 151..................... F : L'nexcasea eoccroi Doc 1151 . .................. " ; t'nexposea control Doc '155..................... F 1 -Ur exposea con:roi Doc '153..................... p Air exposea control Doc '153...................... F .Air exposea control Doc '151.............. p, 33 Doc '151............ ......... p 1 50 j Doc % 161 .................... F I :o 1 0 3 5 0 3 3 0 3 5 0 j 5 0 3 6 0 3 6 11 4 j ia.o A 41 4 15 32 10.4 42 ; 30 1 15.3 15.4 52 40 4i 5 4 3 I --1 -- l--, -- -- --1-- i , 14.5 . 33 ' 13.4 45 | 53 j i: I 14 53 ( 11.1 I . 10-5 ; 33 13*6 55 > '2 45 ; 43 5 ! 13 2 1 i 14.5 t 54 12-7 45 ! 43 3! i 1 ! 15.5 ' 33 ! 11.2 43 j 30 i 4 1 3 1 1 11 '5 . 12.2 33 ; 33 3! o 1 , 14.5 32 23.5 25 3 ! s 1 ` 15.5 55 15.3 46 42 2 3 I 13 46 14 51 37 0i 2 , 15 55 :s.: v3 1 33 5, 2 1 ' 15.5 ' 55 ' 17.3 33 31 : II 10.5 , 33 13.3 33 . 40 10 1 15.5 i 35 , 13-4 55 j 42 1 | 15.5 1 56 12.3 i 53 i 43 !Q j 1 II adjacent to the iea. The flammability of vm\ i ciiior.de precludes such severe leaks if this haz ard of vinyi chionde is to be controlled. Industrial Hygiene Standard The data presented indicate that little like lihood of injury vouid be expected if repeated daiiy 7- to S-hour exposures are iimited to 100 ppm or less. Altkougn the ievei of 100 ppm may not ap pear to oner any margin of safety since rats exposeu repeatedly to this levei were very siizhdy affected, the vast amount of human experience that is available tvhiie operating under an MAC of 500 ppm indicates that injury is not likely. Likewise the effects of even rather severe over exposure are not serious, hence this levei seems reasonable. A time-weighted average lor ail exposure shottid probabiy not exceed 50 ppm. Vinyi chloride (CH,=CHC1) is a monomer used in very iarae nuanuties in the nroduction of piasties. Repeated exposures of laboratory ani mals to several concentrations of vinyl chlorine in air were conducted to determine the chronic toxicity of this material towards animals in or der to assess the hazard to humans. Vinyi chlo ride was found ro have a slight capacity to cause liver mil kdnev iniurv nn renented exposures. Male ami female rats showed micronatholoaical ciianz"' after repeated daiiv 7-hour exnosures at 5 00 ppm for 4 .5 mon:hs. Re perued 7-hour ex* posures at 200 ppm for six months resulted in micropathoiogicai changes in the livers of rab bits and statistically significant increases in the average weight of the iivers of male and female rats but no detectabie changes in dogs and guinea pigs. Repeated 7-aour exposures at 100 ppm resulted in iiight increases in the average weight of rat livers, the other species were not affected. All species studied tolerated repeated daiiy 7-hour exposures to 50 ppm for six months with no detectable injury. Repeated daiiy 1-hour exposures at 200 and 100 ppm of vinyl chionde were without effect, longer exposures caused a slight increase in liver weiznt. The standard for evaluating reguiar daiiy 7to 5-hour exposures may be defined as the con centration beiow which practically all analytical results must fall. The value of 100 ppm is sug gested as this standard tor vinvi chloride, with a time-weighted average for ail exposures not to exceed 50 ppm. References 1. MxnuMctunnc Chetnihii .Usoe. Cliemtcal Safety Data Slim SO * iu 11054). 2. vow OfTriNGEN. tV\ F.. 7* e /fnfnncnntca Ihrdrororbon*. Toxicity nwi Potcnttm Donneri. S. Public Health Servire. P ihlirxtrou No. Ill ) Government Printing Office, U'rtfluincron, D, C. (10551, 3. Masthomatteo. E,. A. M. Fisher. H, Christie, and D Di.s'Ztnnn: Acute Innantion Toticuv of Vinvi Clilo- rulo to I..;i>oratnrv Ammnis. ,4m. In a. II yp. .Imoc. J. SI: 301 i 1000) 4. Si'rrAi'MANv, 0.. hv 13, Lehman <.\n F. Ft,unr. *&& t), iITi -- `.ecnmscnea LcsunpTir.ittei. -\ j*,?sr. Benin. '.US p. 1C3. ;Frem -.:.e traniiatin:*. -.cciOQy cr.<3 //^p'.ene 0/ <nauscnct oii.-enfj r>y Z. z M3 h. ?. s-v;3.;-..:;), . j.I.II. Tr.resnoid L.mii Vpiues for 1-60. AJ/.l Aren. ~-.ur. ileaitn .': -:2 . L0G). t:i. K. r,. Jft.: !TM"rovea Communication--rivyer.e tnarus tor Dauv tnnniat'.nn. Am. i'r.G. //yj. .`.isot. /, .23 11355). H.li Farms. Cg-ticea. N'e^r Jersey. :*.3n Purma Company, Louis. M <soun. 0. llzrr.:3 MiiUnq Oomnany, Mount Pleasant, Michigan. Industrial Hygiene Joutuq o.'enceh. Z. C-. V. K. Rowe. E. M. Aoa.ms. D. D. MwCoLi:srsr., a.'.d D. D. Iiushi Vapor Toxicity ot Zthyiene Z-icaionae as Determined by Experiments on Laboratory Animals. .L'MA Arch. Ind. //yp, and Qceup. :Uea. d. i=2 f 1251), Tjrkelso.v. T. R.t M. A. Wolf, F. Ots??. and V. X. F-oive: Vapor Totieitv 01 AJIvl Clilonue as Determined on Lanorntnry Animals. ,lm. Ina. rfyp. Assoc. J. 10: 217 '12531, 3uni avrmae Feeder Pumps, Moaem Meta;cra:t. 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