Document aBzOQ9gxeyo0XVjrMq5e6DOoN

R&S 110847 1 m 9? Z - BIO--HZDICAL RESEARCH P DOCUMENT DESCRIPTION FORM 53 Duplicate in all cards:--> ____i. 68 69 000/ ^0308" year as-1961- Pile number {Right justify [Numeric only] Author(s), as Last Name PS (No Punctuation) and coden for journal as JAMA preceeded-by. one blank space 77 78 yc Sub-Index Code Title of Report; end with space--hyphen-hyphenyspace. Follow with Index Terr?, separated from each other with -comma-space. Avoid other punctuation; do `not abbreviate. 12 .' . 61 62 21 s? / / . / / /'/ 22 'v/^ / c ZZ y inn / . - 23 24 Source (Journal, Vol. Number, Pages, Date) 12 ` 'V;.-., .-f. ^ ,V /y-y,,...:, ' `ftr.f / A J 61 62.31 32 Brief SuT-.t-ry' 61 62 61 62 63 64 /f77 Tft Tj&KMScta/ /**&**'- / <?/'r' tOfiiA/tl-t ^ -'J T s BIRTH DEFECTS IN A COMMUNITY LOCATED NEAR A VINYL CHLORIDE PLANT 0000308 R&S 110848 Gilles P. Theriault and Lise Goulet Department of Social and Preventive Medicine Laval University, Quebec This work 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 R&S 110849 Vinyl Chloride and Birth Defect BIRTH DEFECTS IN A COMMUNITY LOCATED NEAR A VINYL CHLORIDE PLANT The discovery of the carcinogenic action of vinyl chloride monomer in man has swiftly raised the question of the teratogenic pro perties of this chemical substance. The mutagenic capacity of vinyl chloride monomer and its metabolites has been confirmed in vitro within recent months.(' 1-4)' 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.(' 8)' 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 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 population. Using data from Ohio State's Birth Registry (congenital malformations 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 Vinyl Chloride and Birht Defects 2. 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). 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 pi ant is located. They show however that the mothers of the malformed children were less exposed to vinyl chlo ride 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 the study is to confirm the presence of an increase in the frequency of congenital malformations in a community living next to a vinyl chloride polymerisation plant by comparing birth defects in such a community (Shawinigan) with those of another one (Drummondville) chosen as a control. METHOD R&S 110850 There has been a vinyl chloride polimerisation plant in Shawinigan since 1943 which hired 250 men on average over the years. Production has fluctuated .with time. At the moment, the amount of vinyl chloride monomer released in the atmosphere is estimated at approximately 200 ppm. No data is available to estimate the quantity of vinyl chloride monomer released in the air in the past; it is doubtful it was any lower than today. Ten . . (11) workers of the plant were found having died of angiosarcoma of the liver. The plant is surrounded by other heavy industries such as an aluminum refinery plant, a carbide plant, a chemical factory and a pulpe and paper mill. As the city is located in a hollow betv/een hills and predominant Vinyl Chloride and Birth Defects 3. R&S 110851 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 comprise txtile factories one of which handling synthetic 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 could be found at the city only hospital. In both cases, more than 96% of all records could be 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. study: The following abnormalities were not included as such in the a) locomotor apparatus metatarsus varus calcaneo valgus and varus misimplanted toes internal rotation of the foot flat-foot Vinyl Chloride and Brith Defects 4. R& s 110852 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 diformity of the thorax short string of the tongue It was further required, for a child to be considered malformed that defects be diagnosed at the time of the discharge from hospital. Still-births comprised only children still-born at or after twenty weeks of pregnancy. The annual number of live births whose parents resided 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. Vinyl Chloride-and Birht Defects 5. Table II shows that the ratio of malformed children per 1,000 live births were higher in the city where a vinyl chloride polymerization plant is located. This is true for all types of defects except those of the endocrine system. It may also be noted that the mean age of the moth- * er at delivery in Shawinigan is often lower than in Drummondvi11e. 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. 1.56) is located does not extend to multiple malformations. Except for the years 1971-72', the increase in birth defects in Shawinigan is constant over the nine year period of observation. (Figure I) No 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 similar in both cities. However, proportion of malformed chil dren among stillborns is somewhat higher in Shawinigan (21% versus 18%).' This is concurrent with the finding of a greater number of children with birth defects in Shawinigan. DISCUSSION The present study is in agreement with the studies carried out in Ohio, where a higher birth defect rate was observed in a city with a vinyl chloride polymerization plant. However, the presence of other at mospheric 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. R&S 110853 Vinyl Chloride'and Birth Defects 6. %. The congenital defects observed hereby 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 regis ters. It could be expected that certain cases be 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, any particular chemical would produce a specific effect rather than.a broad increase in birth defects generally. The explanation to such an observation could be twofold: R&S 110854 1 - The chemical in the Shawinigan environment produces by itself or in combinaison with other air pollutants a .broad spectrum of developmental defects. This observa tion disagrees with previous studies showing a possible association between vinyl chloride in the environment and central nervous system defects. The problems faced with 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 Drummondville can result from an artifact such as ignoring defects diagnosed diagnosed after the hospital discharge, different diagnosis or different reporting criteria used in the seven hospitals contacted or some inherent lack of comparability betv/een the study and control population. Vinyl Chloride and Birth Defects 7. Further studies are heeded to assert that vinyl chloride causes birth defects in the community living near a polymerization plant. Should this be the case, stringent emission standards will have to be devised. 4 The authors thank Dr. Jacqueline Fabia, epidemiologist from Laval University; Dr. J.M. Frenette and M.R. Rgmillard from Population Registry of the Province of Quebec; Dr. F. Delorme, from Shawinigan Hospital; Dr. M.N. Johnson, B.F. Goodrich Company; 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 is located since 1943 (and where ten cases of angiosarcoma of the liver have been diagnosed among vinyl thloride monomer workers) are compared with the birth defect ratios observed in another city chosen as control. The frequency of conge nital defects is higher in the exposed community. This phenomenon is observed in seven out of the nine years covered by the study. Women who gave birth to malformed children were on average younger in the exposed community. Both sexes are affected equally. These findings are partly in agreement with other already published previous studies and should lead to further researches. R&S 110855 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 chlorcacetaldehyde monomer hydrate" Biochim. Biophys. Acta 442 (3): 405, 1976. 5. DUCATMAN E., HIRSCHORN K. and SELIKOFF I.: "Vinyl c-loride 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. R&S 110856 Vinyl Chloride and Birth Defects 9. R&S 110857 8. INFANTE P.F., WAGONER J.K., McMICHAEL A.J., WAXWEILLER R.J. and FALK H.i "Genetic risks of vinyl chloride" Lancet 734, April 3, 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, Novembre 29, 1.098, 1975. 11. DELORME F. and THERIAULT G.P.: "Ten cases of angiosarcoma of the liver in Shawinigan, Quebec" to the press. * Vinyl Chloride.and Birth Defects TABLE I - Distribution of malformed children / 1,000 live births by parents' place of residence 1966-1974. Shawinigan Drummondville Number of malformed children 124 Ratio malformed children per 1,000 live births 30.8 -- X2 = 12,359, d.l. 1 , p< 0.001 115 19.7 -* R&S 110858 'Viny/T.chJoride and birth defects * ' 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 Sh./Or. Shawinigan Drummondville (4,022)* (5, 875)* Central Nervous (21)** System 5.2 (13) Eye, Ear, Face 3.2 (24) 4.1 ( 8) 1.4 1.27 2.29 Cardio vascular (28) 7.0 (26) 4.4 1.59 Respiratory A. l^esti ve Senital Jrinary . .ocomotor /s*-------- 1 Chromosomal Endocrine ( 9) 2.2 ( 3) 0.5 (12) 3.0 (10) 1.7 (15) 3.7 8) 2.0 (18) 3.1 (.6) 1.0 (49) 12.2 (43) 7.3 6) ....... ( 8) 1.5 1.4 HD TTj 0.3 4.40 1.76 1.19 2.0 1.67 1.07 0 Mean age of mother Shawinigan Drummondville 24.6 22.7 26.7 24.2 24.7 25.6 22.8 27.0 28.5 - 28.7 23.0 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. j? </> o CoJoI CO TABLE III Distribution of malformed children by year and parent's city of residence accordinq to number of defects (1966-1974)*. 0980 U S?U Sill born defectives included Numbej^f live births *** Ratio^ffformed children/1,000 live-births S - Shawinigan D r Drummondvilie i/inyl chloride and birth defects rIGURE l Annual distribution of malformed children / 1,000 live-births by parents city of residence for the years 1966-1974 Malformed children / 1,000 1 i vebirths (19) KTT SHAWINIGAN DRUMMONDVILLE 40 30 20 10 (19)* (16) T>T? ;:| (12) i- ;l P r . f. >.( t . ? 1 S/5 . i M ( V'J L M (ID J. ; - (9) .r i 1 e!J-v:v/ :.V (9) y bv: iV'-lJ O '-a f ff** - j, rf v (.'X Jt 'v4^ 07) ^ 06) y? (21) ifi &:/- U I-:"' aa tf- v *Ai 1966 1967 1968 1969 1970 1971 1972 1973 1974 * Number of children YEAR OF BIRTH 198011 S* R&S 110862 . , 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 DRUMMONDVILLE MEAN AGE OF THE MOTHER Shawinigan Drummondvilie Still birth without malformation (3 7)* 9.2 (64) 10.89 28.3 28.8 Still birth with malformation TOTAL still-biths ratio per 1,000 live births 00) 2.49 (47) 11.69 04) 2.38 (78) 13.27 26.1 27.2 29.3 - 29.1 * number of cases. s, f