Document EqZg9DN3JgobMGpv62mOnZ7j0

R&S 028816 Second Draft Tha CORSILATIGN 07 CLINICAL AND K.WIROXXE.VTAL SURSXa.VTS PCS VXrdCSHS IXPCSZD TO VIXYL CHLORIC -y J c. c The Tjov.' CSctiilcal Co oaay Xidianc, Michigan 7or Presentation at The 1966 Goreor. Research Conference Or. Industrial Hygiene Tilton, Hew Hampshire August 5, 1968 :*r. . -, -'*Wn'' " , '^ R&S 028817 I. INTRODUCTION A careful and comprehensive study of the exposed workmen Is crucial In validating an industrial hygiene standard. In practice, however, the number of substances for which such studies have been reported have been very few. The challenge today In occupational hoaitn is tne development of programs that will h^lp better define tno relationships between stresses in the work environment ana measurable clinical enanges, oo^n as to the significance of tnose changes and as those relation ships can refine our guide lines for cavIronmenta 1 control Although toxicologists nave 'ooomo quite proficient in pre dicting what exposures are likely to be safe for people, there is always some ocuo^ enough human experience has been gained to prove that their predictions are correct. This "proof of the punning" should result from the cor relation of good environmental measurements with the results of a well planned medical surveillance program. This feed back from human experience likely will differ from the animal experimental data in that It will not define a level of exposure which will actually cause injury, at least frank injury. Except in cases where an industrial hygiene standard has noc been applied, the feed back from human experience could be expected, however, to describe a level of exposure which has been shown to be either acceptable or marginally unacceptable* II. VIXYL CHLCRIS2 Vinyl chinnier (CH^CHCl) Is a chemleal of increasing inQUstrla,. importance. ft is a monomer used both in cne polymerisation or polyvinyl chloride resin, Saran and other copolymers, as a chemical intermediate, and as a solvent. R &s 028818 The toxicity of vinyl onloride has boon reviewed by VOl "0 v *"* | i'iuIi v'vi"vvOvj lorxelson, et nl.. ^ 2 ar<u tgi* csr*c*.y oy *. ... t) *"*G yUij -.0 tii'iOii ifTiC aC r*ir'C G i. 3 1.3 vT.O Or**y ^CpC^'CcC Ci'lcCv Oa aCUtrC OVtiI'0Xpw4***O . TorkeLcon,J Lester, ar.a tr.eir co-workers stuaico tne cr*ron-.c toxicity of vinyl chloride or. rats. Torkelson and associates included rabbits, guinea p^.gs ar+o dogs in a scudy oi cf^ec^s from repeated exposure. Using controlled concentrations of 50-500 ppm, Torxelsor, found that repeated seven-hour exposure to 200 ppm caused micropathological changes ir. the livers of rabbits, and at 100 ppm he noted slight but statistically significant increases in the average weight of rat livers. Other animals were unaffected by 100 ppm. Using concentrations of 20,000 and 50,000 ppm Lester found no evidence of lung or other vital organ effects upon repeated dally exposures lasting 92 days at the lower concentration and 19 days at the higher level. However, he also detected some increase in relative weights of the rat liver as well as the spleen. A. T.".e Committee on T.'.resnoie --lmit Values (American Conference of Governmental Industrial r.ygienists), weighing both studies, concluded tost "although the experimental data are conflicting, vhe preponacrancc incicstos a compound of relatively low toxicity with wnicn a threshold lit.it of 500 ppm is consistent. "5 Hunan Toxicity There are few reported effect- from human exposure to vinyl C'UO. -ae exoe.j- -or narcssi- upon acute exposure. At least two -- ,,aus-r-.a- aoa....s --ro roportea from, overexposure to vinyl ch*or-i.de. 0 -r. a ecr.i,rs-_i_c stuoy, Lester, et al.,** exposed oix vo-un-eers .suve-m--auto p-rloas to A,GOO, ,000, 12,000, lo,000 and 20,000 ppm of vinyl chloride. They found the first sighs oi intoxication appearing at S,000-12,000 ppm. No other effects were reported. Earetta, et^ su.,^ exposed human volun teers to 50, 2p0 and pOG ppm for 7 i/2 hours. Their investi gation primarily was concerned with expired air studies, but no clinical changes nor neurological responses were found in the thirteen volunteers upon thorough physical examination. Filatova and Gronsberg^ reported angioneurosls of a spastic character in workers exposed to the monomer in a polyvinyl chloride polymerisation process. Air samples usually varied between 20 ppm and 315 ppm. R&s 028819 *i *'*jl^&r* -VMfci'V.V. R&S 028820 0* Wilson,, et ai.,^ report several cases of acroosteolysis ir. the hands of workmen wo; Wing on vinyl chloride polymerisation processes. No vinyl ch oridc exposure estimates are cltec, hut the nature of the d. .soroer i-..u ....c circumstances o* its appearance surest that the effect may have rosuitd from a "combination of physical .ca^ ar.c persona. idiosyncrasy." ouciu, e w a --., tna c^.u._c<^._ nanliestatlons of a group of 1SS employees working in polyvinyl chloriae plar.ta. Wi-nout quantifying tna exposures to var.y.. chloride ana other substances in the environment ef these men, the authors report the presence of the "narcotic syndrome," asthenic nervous symptoms, Raynaud's syndrome and hepatomeglia. ENVrRGN/ilNTAL ASPECTS The Work environment Subjects included in this investigation have worked in one or both of two manufacturing facilities which use vinyl chloride in polymerisation processes. In both plants the environmental stresses of the work area have been essentially equivalent. There are two airborne materials present lr. the work environ ment: vinyl chloride and vinylidene chloride, the vinyl chloride being present in much higher concentrations than  R&S 028821 6. vinylidene chloride, can be attributed to The overriding presence of vir.yi chloride to relative woo and dinner volatility. During the first of two decades covered in this study the exposures of the workers to via; - c..oride and vir.ylidene chloride were estimated solely ' no.-. techniques. ,*,i' l1. chloride, although beta r..aer: Ir. more recent noa./are.~,._.-.c.,, 1 tech.nlcues have established t.. vinylidene chloride concer.ttvt fc.Vo.'i.^Oa ucv'hv - v j virtually ail vinylidene eh.or C Ce..vC.i w^'u V.Cr.O _OLip v.IV,.. 5 ppm,* and usually detectable .-.ly ir. -race a:r,or.cc. l?cr this reason, all exposure estimates u,,e c in this study ..avc been indexed as "vinyl chloride.1 Cur conclusions, however, must be viewed in the proper context: a work environment with two airborne materials -- vi.nyiidene ch loride believed to be present in nearly trace amounts and vin;yl chloride in substantial amounts. *A recent study of the effects ir. animals of long-term inhalation exposure of vinylider.e chlorine showed tnst continuous 90-day ex posures changes to In rats and guinea pigs at p hematologic, biochemical, pppamthporloooguiccedandnogsroiwgtnnlfiocant parameters, w rate R&S 028822 R&S 028823 IV, Xc.jiCAw Those who have '.vo-v... .. in tro 1 .'... -w tr..... ^eVulr.^ appro c-..so difficulties er.countered in studying a population wr.iar. it sub ject to continuing; change ini often to nixed exposures, it as rare inactual practice to cnec-nsor a stable population wiwn exposure to a single environmental contaminant. it snis respect the population in tnis study Is typical, in that tne exposure has been nixed. Lixewsse, our clinical ir.e*.nods i-uve varied, both as to frequency of examination and use of certain labora tory tests. Until recently our periodic nodical examination has consisted cf a history, physical, chest X-ray, timed vital capacity, urinalysis and minimum hematology, To this basic examination we have added those particular laboratory tests wr.lch appeared , O ro oo 00 NO fa I R&S 028825 PHYSICAL: ANUS-RECTUM IDENTIFYING BODY MARKS DISEASE CATEGORY: CATEGORY IZ (DISEASES OF DIGESTIVE SYSTEM] lo.b c;.2 0.2 'EC i.5 13. C 7.7 3.0 2.G IC.O 3.0 13.4 15.S 6.1 IB.7 13.2 R&S 028826 R&S 028828 I j~r,,T'S'1' "_'- ' * .-5," ' p ';: '5" bh In* x -1 of the study croup tr.d the overall group, "he study group also showed an increase ir. positive responses to the history iter* on "Sidney stone or b*.occy urine," Again, tnis was not reflected in the diagnostic categories, Tney showed a decrease in number of responses to the history questions on 'stomach, liver, unc untes^._nu^ troue^e unc nervous trouble Ci any sorw. Gn p^yw-vt,., ^AiiO_*u#j -*+ -e on--y CuvCyOry *** abnormalities o* One anus a*-- r>_ c v--. ,-,gan, s_r,ce HOv OOr*"* Cut/ -Tt t/"u - tHu* Cui_jCuut/*t/ Cut/CyvJ'uCCj uv dlCate tnat Ytr.'..YU./ ............... .. O..0 uCt Cms-ucr .t..t. - _..0 Ings tc oe 01 cil.ol.cOu. There was r.o difference in everoil diagnostic categories e:;cept for category I", which covered diseases of 11= digestive system where iccc Cui^r.cicc wore recoraec for >.*'*2 s,uoy group thou for the comparison. There were r.o group differences ir. the electrocardiograms or chest X-rays, har.o X-rays or. .r.c lodlvltuUai^ ..n ,he exposed group showed r.o slfr.ificar.t abnormalities ar.d r.o case of acroosteolysis. Ih comparing the mean ESP of the study group with the comparison group, only 116 measurements were available Ir. the comparison group. The mean 33? for the study group was 2.73 (50 observations) and the mean for the control group was 2.89 (116 observations). In addition, all records were Y4*> **''*' >**!&&* *.*' a'-v* '5 u. tsw,-. R&S 028829 V *CJN*-IA' Dop. v pOl V; J v-*V* *, :x t: D GKCm*:w r..o variation in the observe,. obi VC* CCi* ICVC* C* expos :r<-- ana curat-- on c: oxpocu'v^ essential or.vironrr.enta 1 varic ncc. a^c was reeoraoo to tno warccy wnoie year, Obesity ;a^ uofined as the ratio of iVOl^Cv C0 Stanaara Y/C _y.Yt , "The love I oi exposure was oxpressed as whs cumulative tin ;-v:oi^htoci average concentratio * **no proaace oc !/% ar x tins-on-the Job ('?CJ) gave a rr.es.sure of the cumulative oci Data Format aw ^ulw poim we esc pro parse wV.o coccurro^c secs oi cccs i c each nan: his nodical inforana lor, and his er.v1rorate ntaI in formation. All that remained was the Individual matching process and collective analysis* At the tine or each clinic JO fio c/> rOo uoooo ejMSMisaiia R&S 028832 CG -l.\G GA '- VAr.:i.G physics bysioisc os^oo p'.-oc lySCStCSCC S*COC pCC Vi:_l ccp^-oily T**^ S'it l~-~. " Hoccotolos'icol Hemoglobin l.'onr.nioc.'iz Tied blood cells White blood colls Prothrombin time Urine Specific gravity IXG'GPSfOllXY ACG CTJ, T\V V T* 'GD w .. cG" w C, V G c> \/ O 0GG -- GG cOC 0 r r - oc ooG o cGG ooC ooG ooO oGo " 0 V/ G G G O -r c o _ o o o 0 o R&S 028834 R&S 028836 R&S 028837 FIGURE 2 rci ERUS INDEX UNITS o o o O0 o o o 0 0 _ _W_ s J_____ 0c c 20 AO CO CO 100 12.0 KO 160 180 20 TWA, PP,'.' VOI i: `\v 1 '" ' R8lS 028842 FIGURE 3 Figures ore, ov:o ar.d three eho/r the reh-'etodar responses dor three od the shove rj.sd.il3, Eg?, loserae Index end Beta-Protein respectively. Statistical lrr/.M;:.;.;c si' d:: r' ?. Ar. appropriate eucstlsr i_: *.:hat .-..e^_s C- -- wll w ^ he attached to the r-.ii,,e,,ic.-. acdalev ;hrc- atedal incite arc: the Standard hrrov- od c... '.'.a-.-,a. F-Stsaiss'c, ar.a the s,,eJ"o'^` t o' -a' 3D P (A 5*`! pi fet ' il :. '(^ f. i.vv T *\ \ *- . ' *%\f -V.2 >'v . /'' ' ''I'' .^eiuiZc ?.7jff .& '?' ^ V ;.r V ;^:^;'^0 y - ..v "w''r%^':3^TM ' - " vV r s < , - W- fi^,TV l. : v -: cA ' :.:kfo - v.|$ ->:&v ' ii'-rtiv . ' ,;> ,1 : -^4,ii ; ' >V &. :. . il l<TC t ' !- -:. It v -. 1.4V w ,(*A- , ite:; tev; ft* ^ <* 3^S^0.*^.C CCS nr.- u 4 4r4 -- -- S 2>. L-J *v" C , C Bitctolic Blood Pressure 4 o4 .74 4 O.CI3S45 (TV:A) Icterus Index --- - o, C ^4 ^v9 C'.'.'A} 4 5. 52 V 0.C0C00GC0230S522 (TV.'A)4 : Ke.v.OGloBin _ , ' Eein-?rotein '" ' * '/*' ' ' f r Thee<3 functions ;" =13 . v /' -4.CGCOGCO-t^7339 ('I'.VA) " - :4 .-5 4 0.00000:37:3^5 (TWA)3 ^valuatci end presented in "idle 7 os e. function of CIU. ,- ''o kav;?' r " ;')'] I ^vll '.*. . V; i':?*; ? * " :Vf0& '"ill . ;^i ,m W" II, HIP hulie; . ' `A,1 -' .4: CO '-1 *{< o to i j*Mnj Oo 00 u 07 ' ;-> :'^.r , " :" ., . \/-r * t :.: ^ :4 ..' i?';i'i" '. 'I - ,. . . 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Vinyl Chloride." . . ... ''i:.': -i,'r5'- Corjr.iiieo":or.' lr.rosr.olc lir.io Vnluco: . Docu-~ar.ta"ior. or Chreohold . .. ' *^ '''"Vi1 j . , . .. .;.,;i` , . .. . lir.it'.Values, Px-vl'Ec .1/ Ar.orionr. Cor.i'erer.ce cf Governmental Ir.cootrial 0i >:ysic-nltt.3", ; Cincir.naai;; Chlo_.;(irc;6) : :..V;.-vA ` , " VW;\? ,a; '4'''1( s*,J" '-r- /-* ' vv.:" v' '&'*'? yffiy "! do fi w __ ' .j'-Ji'.! by Vinyl Chloride;' ,.Report .' ~ ofa'IV.'o'. Cases.--'. Canadian yag . A a sac. C. fc2: o5t (Anril. loG). > ..> *, hAy99 ' rw"' ^ ^1-.V .r.a.Vl - -v.. a ' . . : y-- .. -v;:.........- -',j/ " v <} V"- >,l i --r. ;-' . ;'\:;C. SpnvV.r.ji- M-|%v1? "W. -# <0, %3I 3fci 'FW<:%`- t? r-Y.i-.y* - P3y$)T tM: 'si' ;k ^Fv^:- Vir.y: : ' *!y>'/4 : .r,.f*." m r't-'>. ^\v-t#:(&i ?9 ?'>V W oroo g 00 cn }$'5 `%i~ `>'^J Ccr * . l'4.\ ^ 1 :-C'5**"' ." . . .'' : IfeV" I.. -4':' -._' IJHwrSfii' i' " VrHtT.Trf'Mv-i*,'-* .- ' - -#&,;*-, '.:. 3-udy o- A^roowicr-c Cclu-^cI V**Cv _ 'A.'' j -' S7 {`03.,, -Soa),* --j .. 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