Document qdgkqyQ63bDRqvNgp95k9rjQG

rnq== / *#5(V|fi SEp- J 1977 - WCHAfta fUiff^Q /? P- i-hrty/^z-/^^I.h^-.K lit^e sj^h 7 tQfy Vinyl Chloride Cytogenetics n&w&ivcO AUG311S77 A* ROSS ADAMS Dante U Picciano, WtD.? lUy E. Flake, M.O.; Peter C Gay, M.D.; end D. Jack KUIan, M.D. TM report present* cytogenetic findings from a group of 309 workers employed for up to 2B years in the manufacture of vinyl chloride monomer at the Texas Division of Dow Chemical U44. Cytogenotle 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 Jhe tyro groupsTtomparison of theseTesultswith reported studies suggests that 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 cohtroUed, minimal-exposure environments. V irtyl chloride (VC) has been reported to be carcinogenic in animals1 J and human beings' and mutagenic in bacteria] test systems.4 * * There have been reports of increased frequencies of chromosomal aberrations in workers exposed to vinyl chloride at polyvinyl chloride (PVO facilities/ * Similar increases were not found upon cytogenetic evaluation of German PVC workers10 nor in our own preliminary investigation of a group of American VC workers.11 One study based on interviews with male employees has indicated an Increased rate of fetal wastage among wives of VC-exposed workmen .involved in polymerization operations.11 We have recently completed cytogenetic evaluation of all cunenriy^mptoyed workers exposed to vinyl chloride at the Dow Freeport) Texas Division. Both vinyl chloride and vinylidene chloride are produced in this plant. Vinylidene chloride has also been reported as mutagenic in bacteria! test systems.1' However, while these Dow workers are involved with the production of both compounds, the degree of contact with vinylidene chloride is far less than the exposure to vinyl chloride. from Occupation*! Health Mwkil Rtte*<cH Dow Chemcal USA Di fte* cLww and KilWtl and OvpwcmMt nf induurul Oow Chamxat u$A, Tana* Ormaen f\ Mate and Car*, f***pwt. TX 77S4S. Material from this report war pretMiled at the Sth International Co<yyei of Human Cenettl Mretco Cy. October IMS. U76 Journal of Occupational Medieine/Vol. 19. No. 8/August 1977 Vinyl chloride monomer has been produced at the Texas Divi sion of Dow Chemical U-5.A. since 1948. There are no vinyl chloride polymerisation 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 in polymerization operations.14 Although the threshold limit values for vinyl chloride had been 500 parts per million (ppm) until 1974. Dow had established a goal of 50 ppm or below m 1959." The current Occupational Health and Safety Administration IOSHA) standard for vinyl chloride is one ppm as a time-weighted-average over an eight-hour workday. We have found that the TWA con centration of vinyl chloride for all VC-related fob classifications was approximately 5 ppm from 1989 to 1975; 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 years prior to 1968 are less reliable, for the purposes of this study, estimates of exposure were calculated for specific job classifications, based on records of both personnel and area monitoring (Table 1). However, actual exposure may 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 time to time. Documentation of such incidents b difficult Methods Our study group was composed of 209 workers who had worked in the vinyl chloride plant for periods ranging between one and 332 months (average, 48.3 months) at the time of this in vestigation. As part of the medical surveillance program for this poup, peripheral blood samples were obtained, and evaluation of lymphocyte chromosomes was performed. Lymphocytes were cultured using a modification of the Moorhead technique.10 Stan dard procedures, as previously described.11 were used for incuba tion. 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 preemployment examination and who. at that time, had no known exposure to chromosome-break- 7 AP00008452 Tabt 1. -- Etfimittd Eisessr* te Vinyl Chleritf* (VC) fr Vinyl Chl4rBHtf!*lS Jeb Clatsilicstwas. Tablt 2. -- Cytscfiwtie Study of 209 Vrarftvr* figtttd ta Vinyl OiforMt. M Omifiut** SltW.-.X r r---' sj~r * Dn-s'B-: lk in Sa*f Oul'.ft Cvt-sl Lit HUm-V! Mu Cttsvc-ti tafn Sn.'irxii fj:.vr PwMte MjttatV W<i;x Mimra Mn' Ml'M1 H'lf S.iH coif:; 4 5j or? i cay Conict * Os t Cl) CeW'el a Os (V.'0 Ce^f'oi S Os (C*>i4i:>ca> Coot's' 1 Os iCn ( Cool's! C Os iCMw<dt 1 Vn>;i Coo;iy C 0: 'C-rjM'i'.'wl C'v. \ 0: Cun ) Os tPp`t) Clu 3 0c Frtijct fi Cwi Uoit Ujuin CitMtM Cipown la fats sr im-w* ;; i* l; "5 11 %i 13 !1 03 07 00 3* OS 13 OS 13 II *? 0 33 33 07 43 19*197| fcfort 1SS0 44 83 44 33 44 33 OS 05 >0 77 114 153 49 71 <0 >3 03 03 07 07 09 09 MK 90 OS 49 73 OS OS 40 73 71 IDS 79 117 01 09 as 9) so 10 0? 07 73 III 28 S3 91 ! 3 80 lit OS OS 05 3 S3 9 l 07 07 07 07 0.7 OJ *w 4 ae*** Nj tf t4t C*-sn:i iH CWDITV Stilt V(| 4xi*tnct. M IXViM sowmi taflt VtftM 209 W*5) 34N IDS 04S 379 eitiox m 14 751 36\ 1 IS 02S 4$S percent aberrations, and the vinyl chloride workers were separated into those with estimated TWA exposure levels of lessthan-1 ppm. from 1-to-5 ppm, and greater-tban-5 ppm. The estimated exposure levels were based on calculations for specific job classification* to which member* of the vinyl chloride study group were assigned. Three categories of aberration were chosen for this analysis; chromatid breaks, chromosome breaks, and the proportion of abnormal cells. As shown in Table 3. no significant differences were found when these groupings were compared on the basis of chromatid aberrations. Results from those workers with estimated exposures of 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 cetts (Table 5). m ail three cases, most of both groups were found to have aero-to-five percent aberrations, and the vinyl chloride workers with the highest level of estimated exposure showed aberration rates not significantly different than those of the con trol group. Findings for both groups, workers and controls, are considered to be within the range of normal variation as seen in ties laboratory. fng agents. The records selected for inclusion In the control group were matched to those of the study group, insofar as possible, for sex. number of cells analyzed. and time period during which the culture was initiated. Age variation between the two groups could not be completely eliminated: the average age or the vinyl chloride workers was 39.5 years (range. 18 to 67 years), and the average age of the pre employment control group was 25.1 years (range 18 to 50 years), Discussion The reports that have appeared, to date, concerning chromosome aberrations in vinyl chloride workers have not been in agreement. This conflict may be due either to the small number of workers studied or to differences in exposure levels, or both. The Swedish group studied by Funes-Cravioto et alu waTcom-1 posed of seven PVC workers who had been exposed for nine to 29 year* and who were found to have an increased frequency of \ chromosome breakage. The level of exposure for this group was Results As shown In Table 2. data from both groups -- vinyl chloride workers and preemplovinent controls -- were scored and com pared on the basis of chromatid breaks; chromosome breaks; tings, dicentrics, and exchange figures; and the proportion of ab normal cells. The proportion of abnormal cells was calculated to show the overall frequency of aberrant cells, that is. the ratio of cells with at least one aberration to the total numher of cells examined. Results, expressed in terms of the mean percentage for these categories of aberration, showed no maim differences be tween the two groups (nr anv o the classifications. Using Chi-square analysis, ii was decided to see if differences in various aberration rate- could be detected within the two groups. Accordingly, hmh groups were divided into those showing *r> to-fivr percent aberrations and those showing Rrea.er-thvt-five 528 Tab!* 2. -- Distributisn of Cbrwutid RMmtlans ItUlM ta Vinyl Cbteridc (VC) Expaur*. tsxfutt n vc* *1 tpm I-S ppn S jpm Ccnttsh - Nt. \t1 9 ii sm an* o- Giw* vita t IH Grtus i% AWmttott aberMim 309 70 l 41 39* 90S tos 77 23 10 20 7S n JCau^ 77s *sew '{wtvtlMiiatniitoinwudaiuiculiroKte wo'XiAeUKiioii* act Wmf*Uajinur WWwiKfW* nmn to nditnud ***> I* ** mifen p* cUiuAuiion Vinyl Chloride Cytogenetics/Pieciano el at AP00008453 V Table 4. -- Ohtrlhutien ef Cbramsto'M Abfnatisw Notaied t Vinyl Chloride (VC) Eipotw*. (ware ts VC l son 15 m >5 sen CMrdl Ha. fc firms 209 70 II 4| 2SS Hef 0ns >hb tfS itmtiia 98 f (mi *rtk JN Ibemeai MS 49 91 K$ N9 RXS-03SS Table 9. -- Distribution ef Abnennsl Cedi Rotated le Vinyl Chloride (VC) Exposure. * Eraoswt to vc < 1 ton 14 ten isn Co*rail Ns. le films Hot firms vim 8SR 4bmiisiH *fl Cni| ith 5H aWmllws 209 70 91 41 ns v *" 4% in 71 n 73 * i 70 30 Xxa - 3J7 plo ts ------- ----------------J reported to have continuously decreased over a period of years thorium dioxide-exposed persons have an Increased rate of liver until immediately prior to the study when VC concentrations in tumors.11 This relationship between chromosomal breakage and the polymerization department were estimated to be 20 to 30 neoplasia strongly suggests that cytogenetic analyses may be a ppm. tseful tool for detecting environmental situations which may be "The \)S. group of 11 PVC workers surveyed by Ducatnun et a!1* associated with increased cancer rbks to the workers. was also repotted to show an increased rate of chromosome The present study is one of several involving Texas plint em breakage following exposures estimated to have been in excess of ployees to investigate the possibility that increased rates of fetal 500 ppm at times- The group of ten German workers Investigated loss or birth defects In offspring are experienced by wives of vinyl by Fleig and Thiess* worked with either VC or PVC or both for chloride workmen and to determine the morbidity-mortality ex periods ranging between six and 34 years and with exposures esti* perience of all past and present VC workers. A search has been mated to have decreased from greater than 500 ppm in 1945 to made for cases of angiosarcoma of the fiver; none have been between 10 and 25 ppm in 1974. Evaluation of this group for in found in our study group (533 individuals! which includes all past creased aberration rates was negative. and present VC workers. Current workers are also being The study of British PVC workers by Purchase et a/.11 concluded monitored as part of the continuing medical surveillance program. that the frequency of cytogenetic 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 the tuttort acknowledge with epprecmSon the technical enistance of Mo A UnCombe and Mis 0. Mans*. the suggestlem of Ms. M.fienge. the editing (Ms. T. 0. Uovd. and the advice of Or. C ft. twobson. medical director of the surveyed group, however, has informed us but while further analyses of the data confirmed the findings of in creased aberrations in workers exposed to "higher" levels of vinyl chloride, no differences between worker and control groups were References 1. Viola PL. 8<gottt A. and Caputo A*. Oncogenic response of ret stun, lungt, and bones to vinyl chloride. Cancer Res 31316-519. 1971. detected upon evaluation of the data for workers exposed to "lower" levels. An earlier report from our laboratory12 concluded that there were no cytogenetic differences of statistical significance be tween a group of 121 workers exposed to vinyl 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 younger than those already settled into jobs. We do not believe, however, that this difference is a confounding factor In our comparison since the dif ference b not great and because It has been shown11 that the cytogenetic change most often associated with aging is chromosome loss, rather than chromosome breakage. On the basb of our negative findings and the conflicting find 2. Maltoni C and tefemine C: Carcinogenicltv to bioassayt of vinyl chloride I. teseareh plan and early results, Environ Ae* 7:387-405.1974. 3. Creech jl and Johnson MN: Angiosarcoma of the liver in the manufac ture of polyvinyl chloride. IOM H150-1S1. 1974. 4. ftamug U. Johansson A. Ramel C, and Wachtmelster C4: The mutagenicity of vinyl chloride after metabolic activation. Ambio 3:194-197. 1974. 5. Maleveille C Bartsch H, Barbin A etal: Mutagenicity of vinyl chloride, chtoroelhylene oxide, chioroacetaldehyde and chioroethanbl. SrocAem ftqphys Res Common 63:363-370. 1975. 6. Bsrtsch H, MalaveiUe C. and Montesano lb Human, rat and mouse Uver-medreted mutagenicity of vinyl chloride in typhirnwrurr strains. Int I Cancer 15:429-437, 1975. 7. Funes-Cravioto F. Lambert 8, Undsten J et al: Chromosome aberrations In workers exposed to vinyl chloride. lancvt 1:459, 1975. 6 Oueatman A. Hirsehhom K. and Selikoff IJ: Vinyl chloride exposure and human chromosome aberrations. Mu,u Aw 31:163-168, 1975. ings reported by 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 9. Purchase IFH, Richardson CR. and Anderson O: Chromosomal and dominant lethal effeett of vinyl chloride, lancet 2:410-411, 197S. 10. Fleig I and Thiess AM: Chromosome analysis after vinyl chloride ex posure. Arheilsmed Sozialmetf Praevenronecf 9:180-283. 1974. verse cytogenetic effects can be avoided in controlled, minimal- '-XpVI. toIran DL Picciano DL and Jacobson Cfl: Industrial monitoring: A toposure environments. Cytogenetic ' dose-response curves, cytogenetic approach. Arm MV Acad Scf 269:4-11. 1975. similar to that suggested here, have been reported for x-irradiated ankylosing spondylitics.14 A-bomb survivors." radium dial paintws.M persons exposed to Thorotrasl22 and workers exposed to 12. infant* Pf, wagoner PC. MeMichael AJ, Waxweiler R|, and Falk H: Genetic risks of vinyl chloride. lancer 1:734-735. 1976. 13 Baruch H, MalaveiUe C, Montesano R. and Tomatfs L: Tissuemediated mutagenicity of wnylidene chloride and 2-ch1orobuud<enc in lead.1* it has also been noted that the groups exposed to radiation Salmonella typhimurwm. Mature 255:641-64], 1975. later demonstrated significant increases in neoplastic incidence. A-bomb survivors, for example, have shown increased .rates of leukemia and thyroid carcinoma;2* radium dwt painters were 14. Occupational Salety and Health Administration: Exposure to vinyl chloride, fedvrel Register !194); 35889-35698. October 4, 1974. 15. Rowe VR: Experience in indiniriaJ exposure control. Ann NY ActdSci 246:306-310. 197$. found to be at increased risk of osteogenic* sarcoma;* and 16. Moorhead PS, Noweft PC Mellman Wl. Betups DM. and Hungerford Journal of Occupational Medicine/Yol. 19, No. 6/August 1977 529 AP00008454 DA' Chromosome preparations of leukocytes cultured hum human ptr.pheul blood n Cell Rm 20 613-616. 1960. 13. KiIupi DI and P<ceuftoD: Cytogenetic surveiNanceof industrial popu lations- In Chemical \fwaemc A>incipi*-t and Mrihodi for The'f Detection, Vd 4, New Voile A Hnllacnder. ed Plenum Press, 1976. pp 321039. 16. Funes-Cravioto et el, Re'e'ence 7, 19. Ducitmjn et <1. Reference *20. FIeg & Thiest. Reference 10. . 21, Purchase et el Reference 9. 22 Kilun et et Reference 1123. Court Brown WM' Human population evtogenetlcs. ,n Frontier* oI Bioioay. vd V. a Nouberger end U Tatum, edt North Holland Publishing. 1967. pp 1-31. 24. Buckton KE. lacobs PA. Court Brown WM. and Doll It; A study of chromosome damage persisting after x-ray therapy for ankylosmg spon dylitis. lancet 2 676-662. 1962. 25. Bloom AO. Sakagome Y, Ava AA. and Nerlbhi S: Chromosome aberrations and malignant disease among A-bomb survivors. A/ner / Pub Hfth 60:641*644, 1970. 26. Vaughan |. Bone disease induced by radiation. Ini Rev ftp Path 1:243096. 1962. 27. fischer P. Coiob E. Kunae-MUhl E. Halm AB et al: Chromosome aberrations in peripheral blood cells in man following chronic irradiation from intamaf deposits of Thorotrast. Radial Res 29 50I-515. 1966 2B. Cana Chapa % Leah CH. Alvaret M, and Sanebet FJ; Chromoseme analysis in males occupationally exposed to lead (Abstract 325)'. in Ab stracts V International Congress of Human Cenet/cs. S Armendares and R Usker, eds. Excerpta Medica. Amsterdam. 1976. 29. Sampson R|. Key CR. Buneher CR. and lijima A: Thyroid carcinoma in Hiroshima and Nagasaki. >. Prevalence of thyroid carcinoma at autopsy. Hiroshima 1957-63. Nagasaki 1951-67. ASCC Technical Report 25-68,1968, 30. Muller |. David A. Rejskova M, and Brezikova D: Chronic occupational exposwe to strontium-90 and radium-225, lancer 2:129-131. 1961. 31. Fischer P. Colob E. Kunze-Muhl L and MUIlner T: Chromosomal aberrations in thorium dioxide patients, Ann NY Acad $d 143:769-766. 1967. e 3 Vinyl Chloride Cytogerietics/Pieciarto et al AP00008455