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INTERNAL COr^E5PONDNC GULF 10973 - A FROM TO Dr. R. L. Gibson SEE DISTRIBUTION at Houston AT IN REPLY REFER TO 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. koy . viuiuu, n.u. RLG:njf Attachments 2 DISTRIBUTION: Or. 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 01679 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 01680 BIRTH DEFECTS IN A COMMUNITY LOCATED NEAR A VINYL CHLORIDE PLANT Gi lies 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, ERA, Contract Number #68-01-2490 CUSAROSS 01681 Vinyl Chloride and birth Defect BIRTH DEFECTS IN A COMMUNITY LOCATED NEAR 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 the wives of vinyl chloride monomer workers (v 8) . However, this rate was established using questionnaires filled out by the workers themselves thus attenuating the strength of any conclusion. (Q) A recent study v , concerning the 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 1968), 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 01682 Vinyl Chloride and Birth Defects 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- viHe 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 (Drummondville). 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 01683 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 pollutants. 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 01684 Vinyl Chloride and Birth Defects 4. 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 01685 jinyl Chloride and Birth Defects 5. The annual number of live births 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 Drummondvi11e, 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, Drummondvi!le 28/116). It would seem therefore that the higher ratio of malformed children in the city where the vinyl chloride plant (RR. 1.56) 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). No 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 Drummondvilie. However, the proportion of malformed children among still-boms is higher in Shawinigan (21% versus 18%). This is not statistically significant. CUSAROSS 01686 Vinyl Chloride and Birth Defects 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 Drummondvilie 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 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 01687 Vinyl Chloride and Birth Defects 7. Drununondvi 1 le 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. J.M. Fredette and M.R. Remillard from the Population Registry of the Province of Quebec; Dr. F. Delorme, from Shawinigan Flospital; 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 01688 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. 0. 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., LINDSTEN 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 01689 Vinyl Chloride and Birth Defects 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 Shawinigan, Quebec" to the press. CUSAROSS 01690 Vinyl Chloride and Birth Defects TABLE I - Distribution of malformed children / 1,000 live births by parents' place of residence 1966-1974. Shawinigan Drummondvilie Number of malformed children Ratio malformed children per 1,000 live births 124 30.8 116 19.7 X2 = 12,359, d.l. 1 , p < 0.001 CUSAROSS 01691 TABLE II Distribution of malformed children/1,000 live births, relative risk and 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 (28) 7.0 (26) 4.4 Respiratory |. tJi gesti ve Genital Urinary Locomotor Chromosomal Endocrine ( 9) 2.2 02) 3.0 (15) 3.7 (49) 12.2 l 6) 1.5 . o) 1 o (X I CO ( 3) 0.5 (10) 1.7 (18) 3.1 ( 6) 1.0 (43) 7.3 ( 8) 1.4 no 0.3 1.27 2.29 1.59 4.40 1.76 1.19 2.0 1.67 1.07 0 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 * Number of live-births ** Number of children with that defect. CUSAROSS 01692 TABLE III Distribution of malformed children by year and parent's city of residence according to number cf defects (1966-1974)*. ot sfects 1966 1967 1968 1969 1970 1971 1972 1973 1974 TOTAL DsD D D DSDSD D S D Shawinigan 610;)(761)(510)(689) (454) (681 ) (466)(677)(438) (648)(396) (636) (372 (583) (368}(540')(408) (660) (4022) Drummondvi (5375) 14 8 10 2 222 33? 4 5 6 7 8 9 10 11 7 16 10 9 11 18 13 14 16 96 88 2 11 4 51 224 13 21 1 1 11 83 21 21 1 .otal 19 n 16 12 8 19 11 14 17 19 16 17 21 124 (31^1) 04.5) (31.4} (13.1) (26 4) (1 3.2} (1 5. 0) 01.8) (484)07.0 (15 2) (228) (21.2 9. 2)(5I.6)(29.6) (41.7) (31.8) (30.8) Sill born defectives included Lumber of live births Patio malformed children/1,000 live-births CUSAROSS 01693 S r Shawinigan D = Drummondvi11e 116 (19.7) . ,i.y] ch 1 oria d birth defects -'IGJRE I Annual distribution of malformed children / 1,000 live-births by parents city of residence for the years 1966-1974 !al formed :hildren / ,000 1ive il rths 09) SHAWINIGAN DRUMMONDVILLE 09} 40 30 20 10 on > 5c C Ccn/5 o. (19)* (16) {12} m n p'^% ImA N ,,, i (17) (16)^1fZI i ____ Ioy3 i-ri-4i.;'. kh' -j mw &*'< m <9> Hyv'I liII. it is*'-r'a iKt <<r;S El i y o u 1967 19o r q 1969 1970 1971 1972 1973 1974 YEAR OF BIRTH Vinyl chloride and birth defects TABLE IV Distribution of still births/1,000 live births by parents place of residence, category of still births and mean age of the mother 1966-1974 SHAWINIGAN DRUMMQNDVILLE MEAN AGE OF THE MOTHER Shawininan Drumnondvi11e Still birth without malformation (3 7)* 9.2 (64) 10.89 28.3 28.8 Sti 11 birth with malformation (10) 2.49 (14) 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 = 0.21, d.1. 1, n.s. * number of cases. CUSAROSS 01695