Document V3Zkq80p16g01YMRMqVky4d9Z

NEOPLASTIC RISK AMONG WORKERS EXPOSED TO VINYL CHLORIDE Rickard I. Waxweiler, William Stringer, Joseph K. Wagoner, Jamas Jonas Division of Field Studies end Clinical Investigations Notional Institute for Occupational Safety and Health Cincinnati, Ohio 43202 Henry Falk and Coleman Carter Division of Cancer and Birth Defects Center for Disease Control Atlanta, Georgia 30333 Introduction As early as 1930 the lint adverse health effects of vinyl chloride (VC) were reported.1 Since then, numerous observations and studies have indicated a wide range of toxicity attributable to the effects of VC on the central nervous system, the liver, the bones of the lingers, and the lungs.*-** Lately, the spectrum of known toxic effects of VC broadened to include malignant neoplasms. Viola et a!.," in 1971, reported the induction of turnon of the skin, lungs, and bones in rats exposed by inhalation to 30,000 ppm of VC for twelve months. However, widespread acceptance of the carcinogenic activity of VC did not occur until early in 1974 after the announcement of three cases of liver angiosarcoma among worken at a single VC polymerization facility in the VS.A*' About the same time, Maltoni reported the same cancerous hepatic effect in animals following exposure by inhalation to VC.** Shortly thereafter, Maltoni and Lefemine14 and Keplinger et a/.** reported the induction of tumors of the brain, kidney, liver, lung, and lymphatic system in mice, rats, and hamsters exposed to VC by inhalation. Consequently, an epidemiological evaluation was undertaken by the Na tional Institute for Occupational Safety and Health (NIOSH) to assets the magnitude and spectrum of neoplastic effects in workers exposed to VC. This study included industrial hygiene surveys, retrospective cohort analyses of mortality patterns, and histopathologic evaluation of tumors. Retrospective Cohort Study Methods Initially, two criteria were established for selection of facilities to be invests gated. Only those facilities that I) had been engaged in the polymerization of VC for at least Afteen yean and 2) had a sizable work force were considered. Following a telephone survey of all facilities in the U.S.A. known to be polymerizing vinyl chloride, four facilities were selected from among the many which met the study criteria. These four plants in 1974 were employing 230, 73, 230, and 230 VC polymerization worken and had been polymerizing VC 40 for 2: made (PVC vinyl COpol; Si: clinic; striae (expo partm menu survey contre as hai PVCc Er assume vinyl ci the res effect using s for inclL nr ucc 013525 Waxyveiler ft at.: Worker* Exposed to Vinyl Chloride 41 for 28, 20, 24, and 32 years, respectively. Vinyl chloride monomer had been made at two of the four plants, as had the compounding of polyvinyl chloride (PVC). All four plants produced various copolymers of VC at different times, vinyl acetate copolymer being common to all four and vinylidenc chloride copolymer common to three. Since environmentally induced cancer often takes many yean to become clinically manifest following exposure to a carcinogen, cohort study was re* stricted to those individuals having achieved five or more yean of employment (exposure) and ten yean since onset of initial employment (latency) in de partments and jobs directly related to vinyl chloride. In each plant the depart ments and jobs with VC exposure were determined following a walk-through survey by NIOSH personnel and review of company process, engineering control, and air-sampling data. Those specific departments and jobs classified as having VC exposure included VC monomer production, VC polymerisation, PVC compounding.* and maintenance. Employment records were initially obtained of every individual who had ever worked at any of the four VC polymerization plants. All personnel records were subsequently checked to identify each individual who had ever worked in Table I Status as of Decemses 31, 1973 or Woeraas with at Least 3 Yiam' Exrosuae and 10 Years since Initial Exfosube to Vinyl Chlcbide Alive Deceased Lost to follow up Toul Total person-years 1,131 136 7 1,294 12,720 (89.0%) (105%) (0.3%) (100%) ( departments or jobs classified as VC-exposed since the beginning of VC monomer production and/or VC polymerization. Follow-up of all study cohort members t was attempted from the time of termination of employment to December 31, 1973. Information from numer ous state and federal governmental agencies and other sources permitted the vital status determination of more than 99% of the 1294 cohort members (Table 1). Persons for whom vital tutus could not be determined were assumed to be alive so as not to overestimate the true risk with vinyl chloride. The death certificates obtained were coded by a nosologist according to the revision of the "International Lists of Diseases and Causes of Death" in effect at the time of death, and then converted into the 7th Revision numbers, using accepted rules of comparability for 133 of the 136 cohort persons who * The PVC compounding department of Plant I was not included became it was located in the same building as a tire-manufacturing operation; thus, mixed eapomres wen anticipated. t Workers who were not considered pen of the cohort study wera also followed up for inclusion in the histopstbology study. * 1 t t t V i i * iea 1 ucc 013526 42 Annals New York Academy of Sciences died before the study-ending date. A modified life-table technique was used to obtain the 12,720 penon-yesrs at risk of dying, according to five-year age group, five-year calendar period, yean of work experience (exposure), and time since onset of exposure (latency) to VC. Comparison was made between the observed number of deaths among the study cohort memben and that expected on the basis of the U.S. white male death rates specific for age, and calendar year and cause. Ruulli Table 2 shows that a tout of 136 deaths occurred among workers exposed to vinyl chloride as contrasted with 126.3 deaths expected. Only two causes of death were in excess among workers exposed to vinyl chloride: "Nonmalignant Respiratory Disease** (6 observed deaths vs. 3.4 expected) and "All Table 2 Mobtauty Extexience among Cohost Wobkebs Exposed to Vinyl Cmlmuk Cause of Death All malignant neoplasms Heart Nonmalignant respiratory diseases Cirrhosis Violent deaths Residual Unknown Total 1CD Code* (140-203) (400-443) (470-327) (311) (800-983) OBS. 33 57 6 2 13 22 | 136 EXP, 23.3 34.7 3.4 4.0 14.2 26.3 0 126.3 SMR 149 t 104 176 30 92 83 108 * ICDae International Classification of Diseases, 7th Revision; OBS.= obwnfltdi EXP.scxpccted: SMR= (Standardized Mortality Ratio)c^*erv*f x 100. t Significant at p <04>S. Malignant Neoplasms" (35 deaths observed vs. 23.5 expected), the latter excess being statistically significant at p < 0.05. When malignant neoplasms were analyzed by site (Table 3), nnut were found for four organ systems: brain and central nervous system (CNS) (3 ob served vs. 0.9 expected), respiratory system (12 vs. 7.7 expected), hepatic system (7 observed vs. 0.6 expected), and lymphatic and hematopoietic systems (4 observed vs. 2.5 expected). The importance of latency when looking for occupationally induced malig nant neoplasia is demonstrated by Table 4. When the excess risk of death due to all malignant neoplasms and malignant neoplasms of each of the four organ systems is compared in the cohort of persons who achieved ten or mom years since onset of exposure versus the subset of persons who achieved 15 or mom years, the excess risk increases in every cause of death. The Standardized Mortality Ratio (SMR) for all malignant neoplasms increases from 149 to 184; for the brain and CNS, from 329 to 498; for the respiratory system, from Waxweiler ft u Cancex Mostality Cancer Mortality All malignant neoplasms Brain A CNS cancer Respiratory system cancer Biliary k liver cancer Lymphatic and hematopaieti. system cancer * Significant at p <0.03. t Significant at p <0.01. 156 to 194; for the hepati, and hematopoietic system system and brain and CN> significant at p < 0.05; an> Since Plant 4 contribtr and since the plant indue prior to the initiation of i plasms was undertaken sep Cancsb Mobtaltty by Lai Cancer Mortality. All malignant neoplasms Brain and CNS cancer Respiratory system cancer Biliary and liver cancer Lymphatic and hematopoietic * Significant at p <0.03. t Significant at p <0.01. v "W ucc 013527 4 wed it age , and tween i that L and tawct nalig- "All SMR 1491 104 176 13 108 erved; txcess were 3 obtpatie items saligieath four more 15 or >9 to from Waxweiler et al.: Workers Exposed to Vinyl Chloride 43 Table 3 CAMCia MOCTALtTY Exfeaiinci among Commit Womeu Exndseo to Vinyl Cmlomk Cancer Mortality AH malignant neoplasms Brain 4 CNS cancer Respiratory system cancer Biliary It liver cancer Lymphatic end hematopoietic system cancer ICO Code (140-205) (193) (160-164) (153-136A) (200-205) OBS. 35 3 12 7 4 EXP. 23J 0.9 7.7 0.6 13 SMR 149* 329 156 1155 t 159 * Significant at p <0.03. + Significant at p <0.01. 156 to 194; for the hepatic system, from 1,155 to 1.606; and for the lymphatic and hematopoietic system, from 159 to 176, Thus, for both the respiratory system and brain and CNS system these excesses of cancer become statistically significant at p < 0.05: and for "All Malignant Neoplasms," at p < 0.01. Since Plant 4 contributed over two-thirds of the person-years to the cohort and since the plant included the three angiosarcomas of the liver announced prior to the initiation of this study, an additional analysis of malignant neo plasms was undertaken separating Plant 4 from the other three plants combined Tails 4 Cancw Mortality y Latency AMONG WOMCtM Exrouo to Vinyl Cmlokbk Cancer Mortality All malignant neoplasms Brain and CNS cancer Respiratory system cancer Biliary and liver cancer Lymphatic and hematopoietic system cancer OBS. EXP. SMR OBS. EXP. SMR OBS. EXP. SMR OBS. EXP. SMR OBS. EXP. SMR miO-Year Latency 35 23.5 149 3 0.9 329 12 7.7 156 7 0.6 1153 t 4 13 159 k 15-Year Latency 31 16.9 IS4t 3 16 49S 11 3.7 . 194* 7 0.4 16061 3 1.7 176 * Significant at p <0.05. t Significant at p <0.01. 44 Annals New York Academy of Science* Wuik[ et al" Tails 5 Cancex Moctalitv among Womens Exposed to Vinyl Chlomm with hlJ-YcAi Latsncy roe Plant 4 vs. Othm Plants Cancer Mortality All malignant neoplasms Brain 4 CNS cancer Respiratory system cancer Biliary & liver cancer Lymphatic and hematopoietic system cancer Plant 4 OBS. EXP. 26 13.7 2 OS 9 4.6 6 0.4 3 1.4 Other Planu OBS. EXP. 5M 1 0.1 2 1.1 1 0.0 0 0.3 (Tails 5). Although the number of deaths in the three other plants is small, there is no evidence to indicate that the observed cancer risk in these plants is any different from Plant 4 for those workers observed 15 or more yean follow* ing initial exposure to VC. Histotatholoot Study Case Number T 2 3 4 5 7 g 9 10 Histologic 1 'Angfemfcoma Angiosarcoma Angiosarcoma Angiosarcoma Angiosarcoma Angiosarcoma Adenocarcinom gomxooQ but Gall Madder ea Adewocarcinoir 11* Aagtettreoaift 12* Angiosarcoma 13 Angiosarcoma 14* Angiosarcoma Methods Irrespective of an individual's meeting the five-year exposure and ten-year latency criteria, in all cases where a tumor or malignancy of any site or liver disorder of any kind was indicated on the death certificate, attempts were made to obtain hospital records, pathology reports, and tissue specimens for evalua tion by a panel of pathologists,f Some cases had previously never worked in a department or job directly related to VC as defined for the retrospective cohort study. These cases were occasionally exposed to low levels of vinyl chloride. Therefore, for these cates latency was defined as the interval between initial employment at the plant and Results As shown in Table 6, of the 14 histologically confirmed cases of biliary and liver cancer among workers from the four plants, eleven cases of angio sarcoma of the liver were diagnosed. All of the eleven had worked at one time or another as reactor cleaners. Case 4 is noteworthy. This individual's only known exposure to vinyl chloride occurred sometime during 1950-1954 at the VC polymerization opera tion. Seventeen years following hit initial exposure to VC, this individual died at the age of 41 of hepatic angiosarcoma--an observation consistent with Alive as of March 1. of diagnosis. ic tenet of carcit ilc, even in the ; rare. ts teen in Table bars) were diav issue reevaluatic ride. Of the ten slastoma multifoi i cell type distril rhieh 33% of th me.'* Of the nin it soma time in r i worked in tower Kiomi the fourtc t Dr. Luis Thomas of the National Cancer Instimta, Dr. Ham Popper of The Mount Sinai School of Medicine, City University of New York, end Dr. Marvin Kuscbner of the Sutc University of New York. I ucc * 013529 CHlouoe amts Other Plants OBS EXP. 3 3.2 1 0.1 2 1.1 1 0.0 0 0.3 tlants is small, these plants is yean follow- wf year r A, - liver ts were made is for evalua- - job directly * cases were r these cases he plant and es of biliary es of angio* at one time ire to vinyl ation operai individual otstent with Jper of The Dr. Marvin Waxweiler et at.: Workers Exposed to Vinyl Chloride 45 Tun 6 Hbtoloqicaily Comfixmeo Lives im Btuaay Cances Cases among Wonxsas Exroean to \mrt Chunude Case Number Histologic Diagnosis 1 Angiourcoroa 2 Angiosarcoma 3 Angiosarcoma 4 Angiosarcoma J Angiosarcoma 6 AngioMtcoma 7 Angiosarcoma 1 Adenocarcinoma of gall Madder or common bile duct 9 Gall Madder cancer 10 Adenocarcinoma of common bile duct 11* Angkaarcoma 12* Angiosarcoma 13* Angkaarcoma 14* Angioaarcoma Age at Total Death Exposure (years) (years) 38 15 38 27 49 22 41 3 43 14 32 13 31 19 Latency Period (years) 15 28 24 17 15 19 19 ! 24 24 71 19 70 21 43 12 12 43 IS 20 43 19 19 44 13 21 * Alive as of March 1, 1975; thus latency, exposure, and ape ate calculated at < ol diagnosis. a basic tenet of carcinogenesis, that the cancer process once initiated it irre versible, even in the absence of further or prolonged carcinogenic stimulus/ exposure. As seen in Tabu 7, tan cancers of the brain (three among study cohort members) were diagnosed on death certificate, pathology report, and/or by tissue reevaluation, to have occurred among workers exposed to vinyl chloride. Of the tan brain cancer cases, nine were classified histologically as glioblastoma multiforme; no histologic diagnosis was available for the tenth. This cell type distribution appears unusual, vis-i-vis the Yale autopsy scries in which 33% of the primary intracranial neoplasms were glioblastoma multiforme.1* Of the nine cases of glioblastoma multiforme, six had worked for at least tome time in the VC polymerization areas, whereas the remaining three had worked in lower VC exposure areas, From the fourteen cases I of primary lung cancer which occurred among workara having at least five yean of exposure and ten yean since initial ex posure to vinyl chloride, tumor specimens were available on eight. Among these eight bronchogenic carcinomas, no cases of squamous-cell or small-cell carcinoma were teen (Table 8), whereat five were classified as large-cell undifferentiated and three as adenocarcinoma. This distribution of cell type is I Twelve subjects with hmg cancer were identified by death certificates. Two addi tional primary lung cancer deaUa among cohort members, which had been mitclaasifiad on tha death certificates, were coofirmad by pathologic evaluation. ucc 013530 s .* 4* ____ .... ----------- 1 ' 46 Annals New York Academy of Sciences Table 7 Bkaim Cancu Cask Histologically Diagnoud amono Woamm Exfosid to Vinyl Chlobidb Cue Number 1 2 } 4 S 6 7 R 9 10 Histologic Dieiaosis Glioblastoma multiform# Glioblastoma multiform# Glioblastoma multiform# Glioblastoma multiform# Glioblastoma multiform* Glioblastoma multiform# Glioblastoma multiform# Glioblastoma multiform# Glioblastoma multiform# Age at Death (yean) 49 44 33 34 36 43 42 31 63 33 Latency (years) 23* 17 30* 13 t * 2411 207 t 2011 211* 19 tl 3t* Study cohort members: interval between initial tzpoturt to vinyl chloride (VC) a bwu. t Non-cohort members: interval between initial employment and death, t Non-cohort cases who had worked in VC polymerization areas. I Non-cohort cases who never worked in VC polymerization areas. not consistent with the hypothesis postulated by Kreyberglf and corroborated by Archer tt a/.1* end Saccomanno tt a/.1* that small-cell undifferentiated end epidermoid carcinomas of the lung are the principal types whose frequency is affected by inhaled carcinogens. Moreover, it differs from the findings of Whitwell tt al.n that adenocarcinoma was the predominant cell type of lung cancer among male workers with asbcsiosis who had been cigarette smokers. Tabu Lung Cancu Casbs Histologically Conpamu among Cohost Wobxebs Exposed to Vinyl CHLOema Case' Number 41 21 31 41 51 61 7 g\ Histologic Diagnosis Larg# cell undiffsrantiatad Largs cell undifferentiated Large cell undifferentiated Large cell undifferentiated large cell undifferentiated Adenocarcinoma Adenocarcinoma Adenoureboma Age at Death (years) 39 40 32 61 61 43 37 72 Exposure (years) 14 13 22 16 ( 19 12 13 Latency (years) 13 It 22 17 17 19 12 22 A Waxwei Often in retr< groups there are r deaths that would i rates. This obser "healthy worker e a disproportionate of self-selection di employment medi> To minimize this * that period follow: whereas previous . workers exposed tr e similar study cone Inhalation studi. demonstrated that ' adenocarcinomas o: ous other tumors in In the present number of deaths d. lung, and the lympi demiologicalty end agent in the ctiolog carcinogenicity of \ strongly supports the of chemical and oth. The epidemiologof many individuals gratitude to the folic of the Southwestern i port, the numerous r helped in defining th. sonnet of the many C status determination oi 1. Patty, F. A, w. r to vapors of sor ports 4$i 194}-1' 2. Luna, D. L. A psattd exposure Assoc. J. 24:265 ucc 013531 WaxweQer et at,: Worken Exposed to Vinyl Chloride 47 Discussion Often m retrospective cohort studies of mortality among occupational group* there are overall deficits of observed deaths when contrasted with tile deaths that would be expected to occur on the basis of U.S. general population rates. This observed deficit of mortality has recently been referred to as "healthy worker effect" " and has been attributed to several factors, including a disproportionate number of newly hired employees still showing the results of self-selection due to good health, or preselection by industry through preemployment medical examinations and other health-screening mechanisms." To minimise this "healthy worker effect," the present study was restricted to that period following ten yean since initial exposure to vinyl chloride. Thus, whereas previous investigators reported an overall deficit of deaths among worken exposed to VC," no such deficit was found either by this study or by a similar study conducted by Nicholson et at.3' Conclusion Inhalation studies by Viola et a/.," Maltoni," and Keplinger et at.n have demonstrated that vinyl chloride induces hepatic angiosarcoma, adenomas and adenocarcinomas of the lung, neuroblastoma of the brain, lymphoma, and vari ous other turnon in a variety of animal species. In the present study of worken exposed to vinyl chloride, an excessive number of deaths due to cancer of the same four sites was found, vit the liver, hing, and the lymphatic and central nervous system. The evidence, both cpidemiologically and histopathologically, points to vinyl chloride as the causal agent in the etiology of such excessive cancer risk. The observation of the carcinogenicity of vinyl chloride. Ant in animals and subsequently in man, strongly supports the need for conducting animal bioassay prior to introduction of chemical and other agents into the industrial or community environs. Acknowledgments The epidemiological study reported here represents the combined efforts of many individuals and organisations. The authors wish to express their gratitude to the following who contributed to this study: Mr. Brace Gehring of the Southwestern Ohio Regional Computer Center for data processing sup port, the numerous personnel from the companies and unions involved who helped in defining the cohort, and Mrs. Qonnda Battaglia, NIOSH, and per sonnel of the many Ohio and Kentucky State agencies that assisted in the vital status determination of the cohort members. Unuscu 1. Patty, F, A, W. P. Yawt k C. P. Wait*. 1930. Acute response of pimea pigs to vapors of some new commercial organic compounds. Public Health Re port* 4S> 19(3-1971. X Urn, D, L A. Gaxrnstac * W. R. aoams. 1963. Effect* of single and re peated expeeures of humans and rau to vinyl chloride. Amer. lad. Hyg. Assoc. 1.24:265-273. 1 } \ t y t ucc 013532 * 4g Annalt New York Academy of Scfenca 3. Kramer, C. C * I. t MOTCHLiR. 1972. The correlation of clinical end en vironment*! mtasmemenis for worker* aipoaad to vinyl chloride. Amcr. lad. Hy(. Aaaoc. J. 33: I#-JO. 4. Veltman, G., C. E Lance. S. June, G. Stein 4 U. Bachnek. 1973. CUnkal nuniftfULioni and torn* of vinyl chloride discs**. Ann. N.Y. Acad. Sd. 144$ 6-17. J. Lance, C. E-, S. June, G. Stein 4 G. Veltman. 1973. Farther muhs in poly vinyl chloride prodoctioo worker*. Ann. N.Y. Acad. Sci. 244: 16-21. 6. Ulis. R- H. Anbcmon, W. j. Nicholson. S. Daum, A. $. Fnotvein 4 I. j, Selkoft. 1973. Prevalence of dheaee among vinyl chloride and polyvinyl chloride worker*. Ann. N.Y. Acad. Sci. >44s 22-41. 7. CaEECH, J. L, Ja. 4 L Make. 1973. Liver diaeait among polyvinyl work er*. Aim. N.Y. Acad. Sci. 246i 66-94. 8. Gediok, P,, R. Muller 4 H. Bxchtelsmeimlr. 1973. Morphology of liver damage among polyvinyl chloride worker*. Aim. N.Y. Acad. Set. 146i 278263. 9. Maxstellee, H. J- W. K. Lelbacm, R. Muller 4 P. Grmok. 1973. Unutwl pienomegalic liver diaea** a* evidence by periioneoecopy and guided liver biopiy among polyvinyl chloride production worker*. Ann. N.Y, Acad. Sd. 344: 93-134. 10. Millie, A., A. S. Tkmtein, M. Chuano, 1. J. Seueott 4 R Warshaw. 1973. Change* in pulmonary function in worker* expoted to vinyl chloride and polyvinyl chloride. Ann. N.Y. Acad. Sd. 246t 42-32. 11. Viola, P. L. A. Biocom 4 A. Caputo. 1971, Oncogenic retponw of rat skin. lung*, and bones to vinyl chloride. Cancer Ret. 31: 316-319. 12. Creech. J. L, Ja. 4 M. N. Johnson. 1974. AngioMrcoma of liver in the manu facture of polyvinyl chloride. J. Occup. Med. !6t 130-131. 13. Maltonl C. 1974. Preliminary report on the carcinogenicity bio-atuy* of vinyl chloride. U.S. Dept, of Labor Informal Fact-Finding Hearing on Pos sible Hazards of Vinyl Chloride Manufacture and Use. 14. Maltoni, C. 4 G. Lefemine. 1973. Carcinogenicity bioaseay* of vinyl chloride: Current result*. Ann. N.Y. Acad. Sci. 246: 193-216. 13. Kefunocr. M. L. J. W. Goooe, D. E. Gordon 4 J. C Calandaa. 1973. In terim remits of eaposure of rats, hamsters, and mice to vinyl chloride. Ann. N.Y. Acad. $ci. 244: 219-220. 16. Manuelnne, E. E. 4 G. B. Soutare. 1971. Glioblastoma multiform*. In Pathology of the Nervous System. J. Mincklev, Ed. Vol. 2t 2028. McGrawHill. Inc, New York, N.Y. 17. Kreyrerq, L 1962. Aetiology of Lung Cancer--a Morphological, Epidennotogical and Experimental Analysis. Norwegian Univenitics Prca*. Oslo, Nor way. 18. Archer, V. E- G. Saccomanno 4 J. H. Jones. 1974. Frequency of different type* of bronchogenic carcinomas as related to radiation exposure. Cancer 34: 2036-2060. 19. Saccomanno. G.. V. E. Archer, o. Auerrach n si, 1971. Histological type* of lung cancer among uranium miners. Cancer 27: 313-323. 20. WHrrwELi, F,, M. L. Newhous* 4 D. R. Bennett. 1974. A study of the his- tological cell types of lung cancer in worker* suffering from aatcatods in the United Kingdom. Br. J. Ind. Med. 31: 296-303. 21. Taserxhaw, 1. R. 4 W. R. Gaftev. 1974. Mprtnlity study at worker* in the manufacture of vinyl chloride and its polymers. J. Occup. Med. 16: 309^318. 22. Bavliss, D. U. J. Dement, J. K. Wagoner, 4 H. P. Blejer. This annal. 23. McMichael, A. J., S. G. Haynes 4 H. A. Tyrol**. 1973. Observation on the evaluation of occupational mortality data. J. Occup. Mad. 17t 126-131. 24. Nicholson, w. J,, E. C. Hammond. H. Serman 4 1. J. Selixoff. 1973. Mor ulity experience of a cohort of vinyl chloride-polyvinyl chloride worker*. Ann. N.Y. Acad. Sci. 346t 223-230. ( I ' ONO COMM! Much attentior exposure and ang vinyl chloride pro. perhaps m human relation between vi ucU of conception stillbirths cod misc Sclikoff u observec 1,000 in a second 1 findings, a compar records aff produc greeter than the r. source,7 however, of pregnancy. Bet of conception are wives of these wor the result of differ* Dualman and of chromosomal b; as competed to cr relation of ebrom. defects in their ctobservasiom, an ei in Ohio naidenu production faciliti, had shown an ex system, leukemia, state vital statistic- The three Ohi. lie in the northea: are situated about * This study wathe AFLdO. Reprmt requests and CMniral Invesi. Room 313, Cineinn ucc 013533