Document mXq60Ory7XLOLpwjbbnxDnQ0

R&S 136418 Vinyl Chloride Cytogenetics Dante ). Picciano, Ph.D.; Ray E. Flake, M.D.; Peter C. Cay, M.D.; and D. jack Kilian, M.D. This report presents cytogenetic findings from a group of 209 workers employed for up to 28 years in the manufacture of vinyl chloride monomer at the Texas Division of Dow Chemical U.S.A. Cytogenetic evaluation results from this group were compared to results found in examination of individuals being considered for employment. Statistical analyses were per formed on a group basis for chromatid aberrations, chromo some aberrations and proportion of abnormal cells; no statistical difference of significance was found between the two groups. Comparison of these results with reported studies suggests than the level of cytogenetic aberrations in vinyl chloride workers is probably related to the length and level of exposure, and that risk of adverse genetic effect can be avoided in cohtroiled. minimal-exposure environments. Vinvl chloride VC' has been reported to be carcinogenic in animals1 ' and human beings' and mutagenic in bacterial test ^vstems a ' There have been reports of increased frequencies of chromosomal aberrations in workers exposed to vinvl chloride at polwmvl chloride iPVO facilities.* " ' Similar increases were not found upon cvtogenetic evaluation of German PVC workers,n nor in our own prelimmarv investigation of a group of American VC workers.'1 One studv based on interviews with male employees has indicated an increased race of fetal wastage among wives of VC-exposed workmen involved in polymerization operations. We have recently completed cytogenetic evaluation of all curremlv-emploved workers exposed to vinvl chloride at the Dow Freeport! Texas Division Both vinvl chloride and vinvlidene chloride are produced in this plant Vinvlidene chloride has also been reoorted as mutagenic in bacteria! test systems." However, while the^e Dow workers are involved with the production of both compounds, the degree of contact with vinvlidene chloride is far less than the exposure to vinvl chloride. F-ot OcrufMlmo.il jod M-dx'jl Ho<*\vrh Dnw Chomic.il USA On. Pic ; ninn .inn X-Imiv mb Deoirtmen m nduMn.ii M.-du or- Dow Chemir.il USA JAnjc Dr- -i.ikf ,md Cjv Fr,*r>or! rx "S4t Sl.ilffial wn !hn report wj> pre'onied at top S[h lnipfojnon.il Comrns, or Human G*mtn . M*mco C'lv Octooer 10-1 o 1976 Vinvl chloride monomer has been produced at the Texas Divi sion o* Dow Chemical U-S-A. since 1948 There are no vmvl chloride polymerization operations. Average exposure levels, as is the case for almost all vinyl chloride monomer plants, have been generally lower than those reported for facilities involved m polymerization operations" Although the threshold limit values for vinvl chloride had been 500 parts per million lppm> until 1974. Dow had established a goal of 50 ppm or below in 1959 15 The current Occupational Health and Safetv Administration (OSHAi standard for vinvl chloride is one ppm as a time-weighted-average over an eight-hour workday. We have found that the TWA con centration of vinvl chloride fpr all VC-related job classifications was approximately 5 ppm from 1968 to 1973: in 1974. TWA con centrations were 1 to 2 ppm. Since 1975. average levels of expo sure have been lowered to less than 1 ppm. Estimates of average exposure levels for the vears prior to 1968 are less reliable. For the purposes of this studv. estimates of exposure were calculated for specific job classifications, based on records of both personnel and area monitoring (Table 11. However, actual exposure mav vary from individual to individual within the same job classification and accidental, short-term exposures of some workers to concentra tions in excess of the standard probably occur from lime to time. Documentation of such incidents is difficult. Methods Our study group was composed of 209 workers who had worked in the vinvl chloride plant for periods ranging between one and 332 months (average. 48.3 monthsi at the time of this in vestigation. As part of the medical surveillance program lor this group, peripheral blood samples were obtained, and evaluation of Ivmphocvte chromosomes was performed. Lymphocytes were ,cultured using a modification of the Moorhead technique.Stan dard procedures, as previously described.'7 were used for incubation, processing, and analysis. Findings were compared to cytogenetic data from a group of 295 'preemployment examinees " who had chromosome evalua tion done as part of routine preemplovment examination and who. at that time, fvid no known exposure to chromosome-break- floprirttod from Journal of Oceu0*ton*l Mdic" AuquiL 1977. Volum* 19. No. 8 PC. 527-530 R&S 136419 Table 1. -- Estimated Exposure to Vinyl Chloride (VC for Vinyl Chloride-Related Job Classification*. Jab Cliifiatwn Suo*vsof RiO gnjmeer Production Engineer 7hn>cai Soeoaiis: Oeyeiooment Lab Han Sum r Qualilj Control lab 'nstrument Man E'ectrician Cowen Unsuiatcrsi Painter Proetilter Machinist Welder iSeiiermaker) Mainirrjnce lUl<iit* Man) Material Handle" Production foreman Shift Foreman Control A 03 iV2 1 Chloride) Control A 0t> rE 4 Cl' Control A Ob iVinvU Control A Co iChlormationl Control 8 Oo I0i> i Chioridel Control C 0t> IChionde & Vinyl) Control C Oo IChiornalionl Class 1 Oo Class 1 Oo IParts) Class 3 Oo Production Clerk Un<r Manager Eitimattd Exposure *n 'arts (nr Million. a* Tm-tVe^hted-Averag* 1973-197* 1960-1972 9*tr i960 1 * 1 53 \ 7 la 32 t 7 a 32 05 0 5 05 1 2 39 7 7 3 7 11 4 IS 2 1 3 *0 73 1 3 *0 73 0 3 3 03 07 7 07 09 09 09 21 1 39 05 05 0 5 I 3 10 73 05 OS 05 1 3 10 7 3 a a 1 109 5 ? 79 11 7 09 09 09 39 5 5 9 3 23 50 80 0 7 0 7 07 *5 7 3 11 1 25 53 9 1 53 30 1! 3 05 05 05 25 5 3 9 1 0 7 07 0 7 0 7 07 07 Table 2. -- Cytogenetic Study of 209 Workers Eso*ed to Vinyl Chloride. No 0* cultures No or -em Chromatid sreaks Crwomosome B'eas flings J-eentnc? and changes Abnormal ceils Worsen I3U2 3 i!a 1 cs 2 IS 3 7S Controls 395 li >: 3 JS s ::s i ss percent aberrations and the vinvl chloride workers were separated into those with estimated TWA exposure levels or lessthan-1 ppm. from 1-too ppm. and greater-cnjno ppm. The estimated exposure levels were based on calculations ror 'peciric lob classifications to which members of the virul chloride 'tuds group were assigned Three categories of aberration were chosen for this anaivsts- chromatid break' chromosome break' and the proportion or abnormal cells As shown m Table 3 no Mgnincant deferences were round when these groupings were compared on the basis or chromatid aberrations. Results from those workers with estimated expo-ureof greater than 5 parts per million are almost identical to those of the control group. Similar conclusions were reached upon evaluation of the data for chromosome breaks -Table 4- and the proportion of abnormal cells iTabie 5c in all three cases, most nr both groups were round to have zero-to-five percent aberrations, and the vinvl chloride workers with the highest level oi estimated exposure showed aberration rates not sigmticantlv different than those ot the con trol group. Findings ror both groups, workers and control' are considered to be within the range of normal variation as >een in this laboratory. mg agents The* records selected for inclusion tn the control group were matched tn those or the *tudv group insour j* possible, tor sex number or cells .maivzed and time period during which the culture was initiated Age variation hetween the two groups could not he completely eliminated- the average age or the vinvl chloride workers was 39 5 vears irange 18 to 6T vears' and the average age of the preemplovment control group was 2o 1 vears range 38 to 50 vears-. Discussion The reports that have appeared to date concerning chromosome aberrations m vinvl chloride workers have nut been m agreement This conflict rm.iv be due either to the small number or workers studied or to dirrerences in exposure levels or noth. The Swedish group studied bv Funes-Cr.ivioto et al`H was com posed of seven PVC workers who had been exposed for nine to 29 vears and who were round to have an increased trequenev nr chromosome breakage The level or exposure for this group was Results As shown in Tank* 2 data from both groups -- vinvl chloride workers and pmemplovment controls -- were scored and com pared on the basis of chromatid breaks- chromosome breaks: rings dicentrics and exchange figures: and the proportion of ab normal cells The pronnrtmn oi ahnnrmal cells was calculated to show the overall frequenev or aberrant cells that is the ratio of cells with at least one aberration to the total number nr cpilx examined. Results expressed lf1 terms nr the moan percentage for these categories oi aherration showed no major differences be tween the* two groups lor ,inv 'if the classifications Using Chi-square analysis it was decided to oe if deferences m various aberration rates could he detected within the two groups Accordingly both groups were divided into those showing 2ernto-five percent aberrations and those showing greater-than-five Table 3. -- Distribution of Chromatid Aberrations Related to Vinyl Chloride (VC) Exposure. Exposure to VC' < i opm 1 5 com * 5 oom Contiols No. in Grout) 209 70 i] 295 S of Group with 05% Aberrations S of Group with > SS Aberrations 90S 7? 30 75 ICS 23 20 25 T, 03i - 7 75 IP = 0 06) boosii'-* 'eye's jus estimales idss-j y\ -aiejiaiinnx 'y -.o^or-r iw '.'essii'iUMns D"o *'SC Mm -naW'l y ftcosc'* lev?'* *y individuals it* *3 -rifnm :invi'CJ'iC**r. Table 4. -- Distribution of Chromosome Aberrations Related to Vinyl Chloride (VC) Exposure. Exwjsur* to VC l ocm 1 5 own > Bum Controls No. in Group 209 10 98 41 295 % af Grows with 05% Aberrations N ot Group with >$S Aberrations 964, 44, 94 6 95 5 94 6 :U) - 0 355 (P * 0 95) Table 5 . -- Distribution of Abnormal Cells Related to Vinyl Chloride (VC) Exposure. ExBOSur* la VC < l som 1-5 DBm > 5 Bom Controls No. ifl Grouo :o9 ?o 98 41 295 \ of Group with 05N Aberrations S al Group with SN Aberrations S4S I6S ?l 29 73 27 70 30 X Hi - 5 9? (PSO 12! reported to have continuously decreased over a period of years until immediately prior to the studv when VC concentrations in the polymerization department were estimated to be 20 to 30 ppm. The U.S. grouD of 11 PVC workers surveyed by Ducatman et al'" was also reported to show an increased rate of chromosome breakage following exposures estimated to have been m excess of 500 ppm at times. The group of ten German workers investigated bv Fleig and Thiess"' worked with either VC or PVC or both for periods ranging between six and 3-4 vears and with exposures esti mated to have decreased from greater than 300 ppm in 19-15 to between 10 and 25 ppm in 1974. Evaluation of this group for in creased aberration rates was negative. The studv ot British PVC workers bv Purchase et a/.-'' concluded that the frequency of cvtogenetic aberrations was increased in 56 exposed workers as compared to 24 nonexposed individuals. Esti mates of the levels of exposure were not given in this report. The medical director of the surveyed group, however, has informed us that while further analyses of the data confirmed the findings of in creased aberrations m workers exposed to "higher'' levels of vinvl chloride, no differences between worker and control groups were detected upon evaluation ot the data for workers exposed to "lower" levels. An earlier report from our laboratory"' concluded that there were no cvtogenetic differences of statistical significance be tween a group of 121 workers exposed to vinvl chloride and a 75person control group. As in the work reported here, there was a discrepancy in the age composition of the two groups, because applicants seeking employment tend to be vounger than those already settled into jobs. We do not believe, however, that this difference is a confounding factor m our comparison since the dif ference is not great and because it has been shown31 that the cytogenetic change most often associated with aging is chromosome loss, rather than chromosome breakage. On the basis of our negative findings and the conflicting find ings reported bv others, we believe that the level of chromosome aberrations in workers exposed to vinyl chloride is probably re lated to the length and level of exposure and that the risk of ad verse cytogenetic effects can be avoided in controlled, minimalexposure environments. Cvtogenetic dose-response curves, similar to that suggested here, have been reported for x-irradiaced ankylosing spondvlitics.-1 A-bomb survivors.radium dial paint ers. persons exposed to Thorotrast.3' and workers exposed to lead.'1' It has also been noted that the groups exposed to radiation later demonstrated significant increases in neoplastic incidence. A-bomb survivors, tor example, have shown increased rates of leukemia and thyroid carcinoma:'0 radium diai painters were found to be at increased risk or osteogenic sarcoma:1*1 and thorium dioxide-exposed persons have an increased rate ot liver tumors n This relationship between chromosomal breakage and neoplasia strongiv suggests chat cvtogenetic analyses mav be a useful tool for detecting environmental situations which mav be associated with increased cancer risks to the workers The present studv is one of several involving Texas plant em ployees to investigate the possibility that increased rates of fetal loss or birth defects m offspring are experienced bv wives ot vinvl chloride workmen and to determine the morbiditv-mortalitv ex perience of all past and present VC workers A search has been made for cases of angiosarcoma of the liver: none have been found in our studv group (533 individuals) which includes all past and present VC workers. Current workers are also being monitored as part of the continuing medical surveillance program. The authors acknowledge with jporeoation the technical ,ii*[jncc ni Mrs A imvnmbe and Mr' D Mensik the `ugeextions nr vtrs M. Benge the editing nt xu T 8 llovd and the advice Or C 8 lacohson References 1 Viola PL. Bigotti 4. and Capuco 4 Oncogenic response of rat skin lungs and bones to vinvl chloride Cancer Re\ 31:516-319. 1971 2 .Maltonr C and Letemme C Caronogenicitv to bioassavs of vinvl chloride. I. Research plan and earlv results. Environ Re< ? 387.J05 1974. 3 Creech IL and lohnson M.V Angiosarcoma ot tne liver m the manuiacCure of polwmvl chloride iQ\l 16:150-151 1974. 4 Rannug L1 lonansson 4. Rampl C. and Wachtmeister C4 The mutagenicity of vinvl chloride after metabolic activation Ambio 3 194-197. 19*4 5 Malaveille C Bartsch H Barbm 4 et al Muueentcitv ot vinvl chloride, chloroethviene oxide, chioroacetaldehvde and chloroethjnol Biochem ftopnvs Res Commun 63 363-370 1975. 6 Sartsch H Malaveille C. and Momesano R: Human rat and mouse liver-mediated mutageniotv oi vinvl chloride m > ivphtrnurium strains Inr I Oncer 15:429-437. 1975 7. Funes-Cravioco F. Lambert 8. Imdsten I et at: Chromosome aoerrations in workers exoosed to vinvl chloride iancvi 1459 1975 8 Ducatman 4. Hirschhorn K. and Selikoff t| Vinvl chloride exposure and human chromosome aoerrations \lujt Ret 31:163-168. 1975. 9 Purchase IFH. Richardson CR. and Anderson D Chromosomal and dominant lethal effects or vinvl chloride Lancet 2 413-411. 19*5. 10 Fleig l and Thiess AM Chromosome analysis after vinvl chloride ex posure. Arbf`ir<mi'd So/ialmed Praevcntimed 9 200-283 1974. 11 Kilian Dl. Picciano Dl and lacohson CB: industrial monitoring .4 cvtogenetic approach Ann sr Acad So 269.4-11. 1975 '2 Inrjme PF Wagoner JK. McM'chael A|. W.ixwe'ler Rl and Falk H' Genetic risks o' vinvl chloride Lance; 1.734-735 1976 13. Bartsch H Malaveille C. Montesano R. and Tomatis l Tissuemediated mutagenicity ot vtnvlidene chloride and 2-chlorobutadiene m 5.1/mone/lj ivnh'munum Va/t/re 255 641-64 3 1 975 14 Occupational Sa'etv and Health Administration Exposure to vinvl chloride Federal Register 39'194i- 35889-35898. October 4 1974 15. Rowe VK Experience m industrial exposure control .Ann Vr Acad So 246:306-310 19*5 16. Moorhead PS Nowell PC Mellman W|. Bathps DM. and Hungerrord R&S 136420 DA Chromosome preparations of leukocvtes cultured rrom human peripheral blood ir> Cell Re< 20:613-616. 1960 17. Kiiian Dl and Picciano D: Cvtogenetic surveillance or industrial popu lations. In Chemical Sforazen* Principle* and \1e!nod< tor Thei' Detection Vol 4 Sew York: A Hollaender ed Plenum Press. 19*6 pp 321-339 18. Funes-Cravioto et al Reterence 7 19 Ducatman et al Reference 8 20. Fle'g 4 Thiess Rererence 10 21 Purchase et al Reference 9 22 Kihan et al Rererence 11 23. Court Brown WM: Human population cvtogenetic* In front re'* of flro/ogv Vo* V A Seuberger and EL Tatum eds. Sixth Holland Publishing 1967 pp 1-31 24. Buckton K. lacobs PA Court Brown WM and Doll R: A studv of chromosome damage persisting after wav therapv for ankvlosmg spon- dvlitis. lancer 2:676-682 1962. 25 Bloom AO. Sakagome Y Awa AA. and Nernshi S. Chromosome aberrations and malignant disease among A-bomb survivors Amer I Pub HUH 60 641-644 19*3 26. Vaufihan I. Bone disease induced bv raduinxi in: fu* m 1 243-346 1962. 2* Piscne* P Colon E kunze-siuhl [ Haim AB e: al Cnroi-no-nme aberration? m peripheral blood cell? m man milowni; chronic eradiation from internal deposits of Thorotrast Radur Re* 29 =105.11* iunn 28 Garza Chapa R Leah CH Alvarez M and Sanchez F| Chromn-ome analysis m males occupationally exposed :o lead Abstract 32* in An. -tract* V mtemanona' Con^'e-* or Human Con.-nr- > Armend.i'e- and R Lisker. eds. Ercernta siedica Amsterdam 19*6 29. Samp*ix> R| CR Buncher CR and imma A Thyroid carcinoma >n Hiroshima and Nagasaki l Prevalence or thvroid carcinoma at autops? Hiroshima 1957-68 Nagasaki 195 1-6" ABCC *echoi< ,n R-cmr; 25-68 !9o8 30 viulier I. David A Seiskova M and BreZ'kova D Chronic occupation al exposure to <tron;ium-90 and radium-225 Lance' 2 129-1 31 1961 31 Fischer P Colob E kunze-Muhl E and Mijltne' T Chromosomal aberrations in thorium dioside patients Ann S'* Acad >c 145 "69-*6h 1967 R&S CO O) r4o*