Document GKVV3oepoeKxLre1gqq4gZNKN

Reprinted by the U S. DEPARTMENT OF HEALTH, EDUCATION. AND WELFARE PUBLIC HEALTH SERVICE from TERATOLOGY, Vol. 17, No. 2, April 1978 'j ' Congenital Central Nervous System Malformations and Vinyl Chloride Monomer Exposure: A Community Study LARRY D EDMONDS,1 CAROL E ANDERSON, J WILLIAM FLY NT. JR and levy m James Chronic Diseases Division, Bureau of Epidemiology, Center for Disease Control, Atlanta, Georgio 30333 ABSTRACT incidence rates for central nervous system (CNS) malforma tions in infants born to residents of Kanawha County, West Virginia, 1970 1974, were significantly higher than comparable United States rates during those years. Since Kanawha County contains a polyvinyl chloride (PVC) polym erization plant, a case-control study was conducted on the possible relationship between the occurrence of CNS defects and parental occupational or residential exposure to vinyl chloride monomer emissions from this plant. No relationship with parental occupation was found While a tendency was noted for residences of case families to be located in an area northeast of the plant, this observation did not entirely correlate with existing data on local patterns of wind direction and air pollution 4 L Partly because of high rates of congenital anomalies of the central nervous system (anencephaly, spina bifida, and hydrocephalus) in three Ohio communities where polyvinyl chlo ride polymerization (PVC) plants are located (Infante, '76), there has been: concern that vinyl chloride monomer (VCM). released dur ing PVC production might be teratogenic through either occupational or residential ex posure of parents. Further study in one of the Ohio communities revealed no association with parental occupation and no evidence that parents of children with defects lived closer to the local PVC plant than parents of controls (Edmonds et al., '75). To enlarge on these ob servations, incidence data on birth defects available for the years 1970-1974 through the Birth Defects Monitoring Program (BDMP) at the Center for Disease Control were reviewed for other communities with PVC polymeriza tion plants. The BDMP is a nationwide program developed to monitor current inci dence of birth defects as recorded in hospital discharge diagnoses (DHEW, Center for Dis ease Control, Bureau of Epidemiology, '74). Of 40 PVC polymerization plants in the United States (DHEW, Environmental Pro tection Agency, '75), 17 are located in counties which in 1974 had at least one hospital par ticipating in the BDMP. In 10 of these 17 counties, BDMP data included information on fewer than 50% of all county births and were therefore excluded from further analysis. In the seven remaining counties, two had rates of central nervous system (CNS) defects in in fants born in 1970-1974 that were significant ly higher than national BDMP rates for those years: Lake County (Painesville). Ohio, the site of the previous investigation (Infante, '76; Edmonds et al., '75), and Kanawha Coun ty (Charleston), West Virginia. A detailed epi demiologic investigation was undertaken in Kanawha County. METHODS Two sources of data were used to identify all infants with a CNS defect (H-ICDA, 2nd edi tion, codes 740.0-741.9) born in the period from January 1, 1970, through December 31, 1974, whose parents were Kanawha County residents at the time of the infant's birth. One source was case listings obtained from the two BDMP hospitals in the community, which accounted for 95% of all reported county births. For the second source, the West Virgin ia State Department of Vital Statistics iden- Received June 7, '77 Accepted Oct 23. `77 1 Addrew reprint request* lo Larry D Edmondi, M-S P H . Birth Defects Branch. Chrome Dinram Division, Bureau of Epidemiology Center for Disease Control, Atlanta. Georgia 30333 Teratology <i978t il. 137 U2. CUSAROSS 02323 RRE- 5PONDNC Dr. R. L. Gibson AT Houston IN REPLY REFER TO TO SEE DISTRIBUTION AT date February 24, 1978 SUBJECT: Birth Defects in a Community- Located Near a Vinyl Chloride Plant and a Final Report on the Epidemiology Study-'"' Birth defect ratios observed in Shawinigan where a vinyl chloride plant, once partially owned by Gulf, has been located since 1943 (and where 10 cases of angiosarcomas of the liver have been diagnosed among vinyl chloride monomer workers) are compared with birth defects in a control city, Drummondville. The frequency of congenital defects is higher in the exposed city. Also, enclosed is the final report on the vinyl chloride epidemiology study. RLG:njf Attachments 2 DISTRIBUTION: Dr. F. D. Gassaway Dr. W. A. McClellan Dr. R. T. Cheng Mr. B. H. Gambrill Mr. C. R. Grimes Dr. G. F. Huff Dr. H. N. MacFarland Dr. H. T. Miller Mr. H. E. Runion Mr. R. E. Rutherford CUSAROSS 02324 MANUFACTURING CHEMISTS ASSOCIATION 1825 CONNECTICUT AVENUE, N.W. WASHINGTON, D. C. 20009 (202)483-6126 / December 30, 1977 TO: Technical Panel on Vinyl Chloride Research Gentlemen: Dr. Gilles Theriault of the Department of Medicine, University Laval, Quebec, Canada has made available to MCA a copy of his paper entitled "Birth Defects in a Community Located Near a Vinyl Chloride Plant". Dr. Theriault presented this treatise at the Annual Meeting of the American Public Health Association. Your copy of his paper has been enclosed. Sincerely JTS:ec Enclosure J. T. Seawell Project Manager Vinyl Chloride Research CUSAROSS 02325 BIRTH DEFECTS IN A COMMUNITY LOCATED NEAR A VINYL CHLORIDE PLANT Gilles P. Theriault and Lise Goulet Department of Social and Preventive Medicine Laval University, Quebec This study was supported by the Environmental Health Hazard Project of the American Public Health Association under a contract with the Office of Toxic Substances, EPA, Contract Number #68-01-2490 CUSAROSS 02326 Vinyl Chloride and birth Defect BIRTH DEFECTS IN A COMMUNITY LOCATED HEAR A VINYL CHLORIDE PLANT The mutagenic capacity of vinyl chloride monomer and its me tabolites has been confirmed in vitro within recent months The presence of chromosomal aberrations at abnormally high levels in the lymphocytes of vinyl chloride monomer workers has also been reported (5-7) . Studies showing the presence of birth defects in humans follow ing exposure to vinyl chloride monomer are, however, much less convincing. The rate of fetal mortality and abortion has been noted to be higher than expected in tne wives of vinyl chloride monomer workers However, this rate was established using questionnaires filled out by the workers themselves thus attenuating the strength of any conclusion. A recent study (9) , concerning tne oncogenic and mutagenic risks of residents in communities where there are vinyl chloride producing plants, suggests the existence of an association between the presence of such plants in a population and elevated rates of malformations in the popu lation. Using data from Ohio State's Birth Registry (congenital malforma tions have been reported since 1963), the author compared the rate of birth defects in three cities where vinyl chloride polymerization plants are located, with rates observed in other cities of the same State. The study shows that the rate of birth defects is higher in these three cities than in the rest of the State. The difference was particularly marked for malformations of the central nervous system, upper digestive system and the feet (club-feet). CUSAROSS 02327 Vinyl Chloride and Birth Defects J 2. Using data from a different source (Center for Disease Control's Hospital-based Birth Defects Monitoring Program) other authors confirm that the rate of defects of the central nervous system is higher in Pains- ville Ohio where a vinyl chloride plant is located. They show, however, that the mothers of the malformed children were less exposed to vinyl chloride than the control mothers and thus conclude that the high rate of defects is not related to exposure to vinyl chloride. Moreover, in another city where a vinyl chloride plant was located, the rate of birth defects was not higher than predicted. The aim of this study is to confirm the presence of an increase in the frequency of congenital malformations in a community located next to a vinyl chloride polymerization plant by comparing birth defects in such a community (Shawinigan) with those of a control community (Drummondvino). It is a pilot study. Had it shown no excess of birth defects in the studied community, there would have been no reason to pursuit the research; on the other hand, should any excess be found, it will be neces sary to go ahead with more studies before stating that an association between vinyl chloride monomer and birth defects does exist in man. METHOD There has been a vinyl chloride polimerization plant in Shawinigan since 1943 which has had a workforce of 250 men on average. Production has fluctuated with the times. At the moment, the amount of vinyl chloride monomer released into the atmosphere is estimated at approximately 200 ppm. No data is available to estimate the quantity of vinyl chloride monomer released into the air in the past; it is doubtful it was any lower than today. Ten workers of the plant were found to have died of angiosarcoma of CUSAROSS 02328 Vinyl Chloride and Birth Defects 3. the liver The plant is surrounded by other heavy industries such as an aluminum refinery plant, a carbide plant, a chemical factory and a pulp and paper mill. As the city is located in a hollow between hills and predominant winds blow from the industries toward the residential zone, the community has been exposed to relatively high concentrations of atmospheric pol1utants. Drummondville is also an industrialised city. Its population (31,000) shows an age and sex structure similar to Shawinigan (29,000). Its major industries consist' of textile factories, one of which handles synthe tic fibers, a lamp factory and many small businesses. It is located fifty miles south west of Shawinigan. DATA SOURCES Data concerning birth defects were obtained from the files of hospitals where the women residing in the two cities give birth. For geographic reasons, Shawinigan data were obtained from six regional hos pitals while Drummondville data were acquired at the city's only hospital. In both cases, more than 96% of all records were retrieved. Malformed children were ascertained through the following sour ces: the mother's file, the newborn's file, the obstretric room's daybook and the autopsy reports. DEFINITION OF A BIRTH DEFECT Birth defects included in this study were those either apparent at birth, or discovered by an X-Ray or a laboratory examination (this ex cludes heart defects) or described in autopsy reports. CUSAROSS 02329 Vinyl Chloride and Birth Defects A. study: The following abnormalities were not included as such in the a) locomotor apparatus metatarsus varus calcaneo valgus and varus mis implanted toes internal rotation of the foot flat-foot b) genitals cryptorchidism hydrocele undescended testes phimosis c) cutaneous-mucus membrane nevus vasculosus, nevus venosus mongolian spots cavernous hemangiomas pilonidal sinus begnin teratoma d) others pectus excavatum stenosis of external urethral meatus thymus hypertrophia small cleft palate eyelid ptosis minor deformity of the thorax short string of the tongue. For a child to be considered malformed, the defects had to have been diagnosed at the time of the discharge from hospital. Still-births comprised only children still-born at or after twenty weeks of pregnancy. CUSAROSS 02330 Vinyl Chloride and Birth Defect s 5. The annual number of live birtiis of parents residing in each city was obtained from the Quebec birth registration file. RESULTS Table I gives the distribution of malformed children by parents' place of residence. The Chi square test indicates that the difference is significant between the two cities. Table II shows the ratio of malformed children per 1,000 live births by type of malformations. All types of defects except those of the endocrine system are higher in the city where the vinyl chloride polymeri zation plant is located. Although the mean age of the mother at delivery in Shawinigan is often lower than in Drummondvilie, it is not statistically significant. Table III shows the distribution of malformed children according to number of defects per year and city of residence. Among malformed chil dren, the proportion with multiple malformations is similar in both cities (Shawinigan 28/124, Drummondvilie 28/116). It would seem therefore that the higher ratio of malformed children in the city where the vinyl chloride plant (RR. 1.55) is located does not extend to multiple malformations. Except for the years 1971-72, birth defect ratios are higher in Shawinigan over the nine year period of observation (Figure I). Mo clear reason could explain this difference in the ratio of defects each year. Table IV shows that the ratio of still-births per 1,000 live births is somewhat higher in Drummondvi1le. However, the proportion of malformed children among still-borns is higher in Shawinigan (21% versus 18%). This is not statistically significant. CUSAROSS 02331 Vinyl Chloride and Birth Defect 6- DISCUSSION The results of the present study concur in part with those of studies carried out in Ohio, where a higher birth defect rate was observed in a city with a vinyl chloride polymerization plant. However, the pre sence of other atmospheric pollutants in the environment of Shawinigan should be noted. The present study does not permit linking the observed phenomenon to a particular pollutant be it vinyl chloride or any other teratogenical agent. Congenital defects observed in Shawinigan as well as in Drummondville were higher than those observed in Ohio, Differences could be accounted for by the data collection method. The present study gathered data from hospital records while the Ohio study used birth registers. It is possible that certain cases are not reported to a state register. It is puzzling to observe that the increase of birth defects is in the same order of magnitude in several organ systems. Usually, particu lar chemical would produce a specific effect rather than a broad increase in birth defects generally. The explanation for such an observation could be twofold: 1 - The chemical in the Shawinigan environment produces, by itself or in combination with other air pollutants, a broad spectrum of developmental defects. This observation is not in line with previous studies which show a possible associa tion between vinyl chloride in the environment and central nervous system defects v . The problems encountered in Shawinigan could be of a different order of magnitude than those seen elsewhere. 2 - Even if careful attention was given to the collection of data and even if more than 96% of all births were reviewed in both cities, the apparent difference between Shawinigan and CUSAROSS 02332 Vi!,yl Cnlnride and B i >' th Defects 7. Drummondvi11e could result from an artifact such as ignoring defects diagnosed after the hospital discharge, different diagnosis or different reporting criteria used in the seven hospitals contacted or some inherent lack of comparability between the study and control population.. Further studies are needed to support the assertion that vinyl chloride causes birth defects in the community located near a polymeriza tion plant. Should this be the case, stringent emission standards will have to be devised. The authors thank Dr. Jacqueline Fabia, epidemiologist from Laval University; Dr. O.M. Fredette and M.R. Remillard from the Population Registry of the Province of Quebec; Dr. F. Delorme, from Shawinigan Hospital; Dr. M.N. Johnson, B.F. Goodrich Compagny; Dr. L.D. Edmonds, Center for Disease Control, for their help and comments. ABSTRACT Birth defect ratios observed in a community where a vinyl chloride polymerization plant has been located since 1943 (and where ten cases of angiosarcoma of the liver have been diagnosed among vinyl chloride monomer workers) are compared with the birth defect ratios ob served in a control city. The frequency of congenital defects is higher in the exposed community. This phenomenon is observed in seven out of the nine years covered by the study. Both sexes are affected equally. These findings concur in part with other previously published studies and should lead to further research. CUSAROSS 02333 Vinyl Chloride and Birth Defects 8. REFERENCES 1. RANNUG V., JOHANSSON A., RAMEL C. and WACHMEISTER C.A.: "The mutage nicity of vinyl chloride after metabolic activation" Ambio 3, 174, 1974. 2. BARTSCH H. , MALAVIELLE C., MONTESAND R.: "Human rat and mouse livermediated mutagenicity of vinyl chloride in S. Typhimurium strains" Int. J. Cancer 15, 429, 1975. 3. HUBERMAN E. , BARTSCH H. and SACHS L.: "Mutation induction in Chinese Hamster V 79 cells by two vinyl chloride metabolites, chloroethylene oxide and 2-chloroacetaldehyde" Int. J. Cancer 16, 639, 1975. 4. ELMORE J.D., WONG J.L., LAUNBACH A.P. and STREIPS U.N.: "Vinyl chlo ride mutagenicity via the metabolism chloroxirane and chloroacetaldehyde monomer hydrate" Biochim. Biophys. Acta 442 (3): 405, 1976. 5. DUCATMAN E., HIRSCHORN K. and SELIKOFF I.: "Vinyl chloride exposure and human chromosome aberrations". J. Mutation Res. 31, 163, 1975. 6. FUNES-CARIOTO F., LAMBERT B., LINOSTEN J., EHRENBERG L., NATARAJAN A.T. and OSTERMAN-GOLKAR S.: "Chromosome aberrations in workers exposed to vinyl chloride". Lancet, i., 459, 1975. 7. FOMENKO V.N., KATOSOVA L.D. and PAVLENKO G.: "Cytogenetic analysis of the peripheral blood in workers exposed to vinyl chloride polyme rization". Gigiena Truda i Professional'nye Zabolevania Vol. 9, Sept. 1976, 48-50. CUSAROSS 02334 Vinyl Chloride.' and Birin Do frets 9 8. INFANTE P.F. , WAGONER J.K., McMICHAEL A.J., WAXWEILLER R.J. and FALK H.: "Genetic risks of vinyl chloride". Lancet i: 734, 1976. 9. INFANTE P.F.: "Oncogenic and mutagenic risks in communities with polyvinyl chloride production facilities". Annals N.Y. Aca. of Sciences, 271, 49, 1976. 10. EDMONDS L.D., FALK H. and NISSIM J.E.: "Congenital malformations and vinyl chloride". Lancet, ii: 1098, 1975. 11. DELORME F. and THERIAULT G.P.: "Ten cases of angiosarcoma of the liver in Shawinigari, Quebec" to the press. CUSAROSS 02335 Vinyl Chloride and Birth Detects TABLE I - Distribution of malformed children / 1,000 live births by parents place of residence 1966-1974. Shawlnigan Drummondvi11 e Number of malformed chiIdren Ratio malformed children per 1 ,000 1 i ve births 124 30.8 116 19.7 X2 r 1 2,359, d.l . 1 , p < 0.001 CUSAROSS 02336 Distribution of malformed children/1,000 live births, relative risk ami mean age of mother at delivery time, by type of malformations and city, 1966-1974. Ratio for both sexes Relative Risk shawinigan Drummondvi11e Sh./Dr. (4,022)* (5, 875)* Central Nervous (21)** System 5.2 (13) Eye, Ear, Face 3.2 (24) 4.1 ( 8) 1.4 Cardio vascular (23) 7.0 (26) 4.4 Resp i ratory w Li i ges five Cenita1 Urinary Locumotor Chromosomal Endocrine ( 9) 2.2 (12) 3.0 (15) 3.7 \ 8) 2.0 (49) 12.2 ( 6) 1.5 7"(T) ( 3) 0.5 (10) 1.7 (18) 3.1 ( 6) 1.0 (43) 7.3 '( 8) 1.4 ( 2) 0.3 1.27 2.29 1.59 4.40 1.76 1.19 2.0 1.67 1.07 0 * number of live-births ** Number of children with that defect. Mean age of mother Shawinigan Drummondvi11e 27.2 27.5 24.6 22.7 28.7 23.0 26.7 24.2 24.7 25.6 22.8 27.0 28.5 - 28.8 23.8 29.7 24.6 21.7 29.2 36.2 26.4 1 CUSAROSS 02337 TABLE III Distribution of malformed children by year and parent's city of residence according to nurbc^ cf defects (1966-1974)*. Sill born defectives included Number of live births Ratio malformed children/1,000 live-births CUSAROSS 02338 S - Shawinigan D r Drumirondvi 11 e 1 formed ildren / Annual distribution of :nal for,'nod children / 1,000 live-births by parents city or re dence for years 1566-1974 CUSAROSS Number of children YEAR OF BIRTH TABLE IV l_' I L. I I i*J C t_ ^ ^ 2) Distribution of still birtns/1,000 live births by parents place of residence, cateoory of still births and mean age of the mother 1966-1974 SHAWINIGAN DRUMMQNDVILLE MEAN AGE OF THE MOTHER Shawinipan Drumnondvi11e Still birth without malformation (37)* 9.2 (64) 10.89 28.3 28.8 Still birth with malformation (10) 2.49 04) 2.38 26.1 29.3 TOTAL still-births ratio per 1,000 live births (47) 11.69 (78) 13.27 27.2 29.1 X2 = 0.21 , d. 1, 1, n.s . * number of cases. CUSAROSS 02340