Document 5L3qvmNkLVBQGeq0e8RjdJZ94

19 January 1982 Ar Products and Chemicals, Inc. Bex S38. Allentown PA 18105 (215)481-4911 Dr. John Stafford Imperial Chemical Industries, Ltd. P. 0. Box 6 Bessemer Road Welwyn Garden City Hertfordshire AL7 IHD ENGLAND Dear John: The attached article from the Boston Globe Is my first encounter with a report of anglo at the old Monsanto plantl Rs you probably know, this plant closed In 1975. I don't know If this plant was Included In the CMA study or not. I will try to learn more about this case through a friend at Monsanto, but you may have better success if you contact Monte Throdahl or Bill Gaffey directly. This, together with the new Union Carbide case. Is discouraging; but, at least they both seem due to pre-1960 exposures. Best wishes for survival In this unusual winter weather. John/T/Barr Manager, Regulatory Response JTB/sjw cc: Dr. T. R. Torkelson - Dow Chemical Co. AP00018711 -* * . *% * 5tudy of Monsanto plant links |.A ^r-T-' '^1*J . fMIrHatUMaIuHnnIiMWMMAHpM|KljliH(Ii iU,.c.U_Mi,.`iiLMMTy- UTrfJtttCMa MIMMIIiiMMmiIIi mljM- li*n"nitmrmMin mill iNi^JV' Mlt >nn* --ipamMrh. UM(Miw SSSMS^TSS NU"-*kM!am^umaw4uifmc4vt>waiHM-M-.i-Ma-'U-f-rMMc-M-M-(M-hl-aU-aUatif&a, jiracMaartLhrtj l; -/.,< L^fcusi2taanp mM be 1 tfctjMMt OvMsn i pUai mcMmii. 4K--f-c-d-c-uHpj*tMlmMiia*iianJ*uim4*MaaMl--fHLc,ar_da,t*__it -. -- --------- -- , . tfctl m :* Hr Mm ar Mqpta* -- mnaM te Itatar MMuMfcath* ...H*- M-gUijMzDX^MZughi#Z, T. =^-r332 MMI, m iimmamMUranyWim>Mnrhi" SS^B^rnart rt?5ftM*!S* safes -MMt-e. .... jfcMortM ,Wi.'.M1f-1t`1AilmnMait. MI--fiwteMatpM(.yiCM..M---iELgZ-"nM---=gZ-I-io-.--.s--ZTjfXyeigZi--Z-ggZi^!-' *^T lillrhi^ t tNE--naMy iluiii ihraafkoMyhe * pM M Me Mm Mae M i Smt t mwi > h1 **-- yy-' am ma1c11M he ~itii----ar~\m '--"- APOOOt8712 W*/.-:.-' X. EUf..c: H w-. P' ICPHC 2/Sf v" INTERNATIONAL COMMISSION FOR PROTECTION AGAINST ENVIRGNnEkTAL MUTAGENS AND CARCINOGENS ICPEMC Working PapeT TGI /2 */79 Mutagenicity and teratogenicity of vinvl chloride monomer (VCM) Epidemiological evidence Johannes CJemmesen Sioci Mmfgadt 4S. 3100 Coptnhusrn. Dtnmuri (Received t(- September Wli (Accepted 2! September IW>!) The rarity and special character of angiosarcoma hepatis and its association with exposure to vinyl chloride monomer (VCM) has occasionally led to the error that a case of this tumor is tantamount to such exposure. Apart from the possibility that a number of such cases may in the past have been taken for cbolangiocarcinomas. the experience of a British team of histopathologists going over cases from Britain during 1963-1973 has revealed some over-estimate of Use frequency of this lesion, with the additional experience that only 1 of the agreed 14 cases could be confidently associated with exposure to vinyl chloride (Baxter et al., 1977). It follows that exception must be taken to the conclusion that single cases of angiosarcoma hepatis from the surroundings of polyvinyl factories may be taken as evidence of an escape directly from the plants or otherwise. It would, however, be important if mutagenic or teratogenic effects of VCM be demonstrable either in the surroundings of factories or in the domestic environment of workers employed in PVC-producing facilities, and this possibility is tbe subject of the following review. *. * Ii has been tarred to publish this document ts t working paper ter Task Croup I of the teiematiooaJ Commission tot Protection against Environmental Mutasent and Carcinogens (ICPEMC). Tbe views expressed arc those of the author and do not necessarily represent those of the Commission Thr\ are published io ftiaulair discussion and comments. which will be welcomed b> the author. All correspondence and reprint requests should be addressed to the secretarv of ICPEMC Paul H M Lohman. Pb D.. Medicat BiotoakaJ Laboratory TNO. PO Boa 4J. 219,0 AA Rsjswijk (The Netherleadsi Tel. IS.IMT77. teles 3WM pmtnonl (ICPEMC document Ol6M110/t:/0000-0000/S03.7$ C Elsevier Biomedical Press APOOOf8713 An investigation of a possible increased occurrence of birth defects in the surroundings of PVC plants or among the children of workers has been attempted b> Infante (1976) and Infante et a!. (1976). The studies were based on data from 4 Ohio communities, of which 3. Ashtabula. Painesville and Avon Lake, had at least I polymerization facility in operation. Ashtabula since 1954. Avon Lake since 1946. and Painesville since 1946. with a 2nd plant opened in 1967. The 4th community. North Ridgeville. was near to Avon Lake and was without PVC production. Population numbers ranged from 24000 in Ashtabula to 12000 in Avon Lake. Between the census years I960 and 1970 the population of Avon Lake increased by 30$. whereas the populations of Ashtabula and Painesville remained about the same. According to birth-certificate data for 1970-1973. it appeared that while the rate of malformations for the entire State per 1000 live births was 10.14. the rates in the index communities were : Ashtabula. 17.37: Painesville. 18.10: and Avon Lake. 30.33. For these 3 cities with PVC production facilities the differences between observed and expected numbers of malformations in each city wctc significant at the P < 0.01 level according to the x2 last. Nevertheless, the highest rates for malforma tions were found in North Ridgeville. 27.26: and in Geneva. 12 miles from Ashtabula, 25.40, both cities without PVC plants (Infante, 1976.) Infante, furthermore, found an excess of CNS defects among still-births and live births from the index cities, with the exception of Avon Lake. Most of the excess, however, was attributable primarily to Painesville and secondarily to North Ridgevtlle. It was therefore obvious that the findings did not link PVC production with the said anomalies. Edmonds et al. <1975). observing that the increase reported was not uniform and appeared more prominent in the Painesville area, analyzed data collected through the Center for Disease Control's hospital-based Birth Defects Monitoring Pro gramme (BDMP). For 2 hospitals located in cities with polymerization plants. Pottstow-n in Pennsylvania and Painesville in Ohio, they compared CNS* malformation rates for white infants bom during 1970-1974 with the rates for white infants in each Slate. No increase was seen in the Pennsylvania hospital, but an increase, primarily in anencephaly and Spina bifida. w*as noted in the Painesville hospital amounting to 22 cases, or twice the expected. After inspection of the birth-defect registry for Ohio. I more case could be included in the study, bringing the total to 15. Interviews with parents revealed that none of them had worked at either of the 2 PVC plants in Painesville. However. 2 of the fathers of controls had worked at 1 of the plants. A significantly larger proportion of control mothers than case mothers worked (including housewives) within a 10-mile radius of the PVC plant, which was probably a chance occurrence (95$ confidence level). It was concluded that, although the follow-up confirmed a moderate increase in CNS malformations in Painesville. Ohio, no association had been found with vinyl chloride exposure. A further study (Edmonds. 1976) of data from hospitals in Potisiown. Pennsyl vania. and in Painesville, Ohio, revealed no difference between the cases and the controls in possible expc between the cases and cc plants. In Kanawha County t* cases and controls livin association with VCM. In a persona! commun among wives of workers without the use of con attempted a comparisor before and after exposi number of rubber-factor A total of 95 VCM-pol workers was interviewed Interviews were cond pregnancy outcome wet* was the initial item of a No data were obtained c rates for the primary' V< separately before and af It should be mention before analysis finding misleadingly. From these data pub tion with those of the fi exposure, the mean pan and for controls 23.0. u Because fetal loss is death rates for the prin group. This reduced the Contrarily the raw* r. for controls was only si study group, so that Pa* The asymmetry in a paralleled with an *$>n exposure, numbered 70 159, respectively, force Further objections w for the plastics industr based on age prior be adjustment to the cor. does not justify comp which requires tndeper Therefore, when the so far of an effect of \ 1 ^a-- AP000I87I4 br:h defect? tn the '* ha? been aiienptcd based on da;s from 4 'n Lake had at lea-t I vvon lake since )9-6. . The 4ih community, out PV'C production. 12000 n Avon Lake, von Lake increased by e remained about the red that u-hi)e the rate 10.14. the rates in the '.10: and Avon Lake. >e differences between were significant at the est rates for malformameva. 12 miles from `6.> ng still-births and live e. Most of the excess, iarils to North RjdgeC production with the . was sot uniform and ` *ata collected through eels Monitoring Pro'lymeriiation plants, ey compared CNS ith the rales for white . ania hospital, but an -ed in the Painesvilk more case could be parents revealed that -esville. However. 2 of x significantly larger ncluding housewives) ` a chance occurrence moderate increase in rjeen found with vinyl n Potuiown, Pennsvl* sen the cases and the w*. controls in possible exposure to \CM Residential histones showed no difference between ihe cases and controls when compared at various distances from the P\c plants. In Kar.awha County the author found a difference in the pattern of residents for cases and controls living wahm 3 miles, but the available data suggested no association with VCM In a persona) communication. Selikoff reported that he had estimated fetal'deaih* among wives of workers exposed to VCM at 7-14 per 100 pregnancies, ahhoush without the use of controls. Referring to this statement. Infame et al. (1976at attempted a comparison of pregnancy outcome among wives of VCM workers before and after exposure, compared with wives of PVC workers and a similar number of rubber-factory workers matched as a group to the VCM workers bv age. A total of 95 VCM-polymcrization workers and 156 rubber and PV'C-fabrication workers was interviewed in October 1974. Interviews were conducted with workers, not with their wives. Questions about pregnancy outcome were contained in a much larger interview questionnaire, which was the initial item or a cross-sectional health survey including physical examination. No data were obtained on maternal age. but. on the basis of paternal age. fetal death rates for the primary VCM exposure group were age-adjusted to the control group separately before and after the husband's exposure. It should be mentioned that Paddle (1976) asked for tabulation of the raw data before analysis finding that age adjustments appeared to have influenced figures misleadingly. From these data published without delay by Infante et al.. (1976b). in combina tion with those of the first publication, the fr' ng observations stand out. Before exposure, the mean paternal age at conce- study pregnancies was 26.4 years and for controls 23.0. with crude fetal dv of 10,1 an 6.9$, respectively, Because feta) loss is known to inert ncreasiog parental age. the fetal death rales for the primary VCM expos group. This reduced the rate for the stud were age-adjusted to the control .fore exposure, from 10.) to 6.1%. Comrarily. the raw rate, after exposus for controls was only slightly influenced ? for the study group versus 6.8$ djustmenl. showing 15.8% for the study group, so that Paddle's objection Wj- .ustified. The asymmetry in age. before exposure, between study group and controls, is paralleled with an asymmetry in numbers of families which, before the husband's exposure, numbered 70 for study families against. 62 after exposure, versus 95 and 159. respectively, for control families. Further objections were raised by Downs et al. (1977) in a critical review prepared for the plastics industry. They pointed oui that matching by age should have been based on age prior before employment not on age at the interview, and that age adjustment to the controls' standard, made separately before and after exposure, does not justify comparison of these 2 values. The use of Maniel-Haenszels lest, which requires independence of the 2 rates being compared, is also found incorrect. Therefore, when the evidence is weighted, it seems that there is no demonstration so far of an effect of VCM as alleged by Infante et a). i APOOOI8715 100 Reference* Bauer, P.J., P.P Anthonj.M; Stveenetal (19771 Angiosarcoma of the liver m Great Britain 1963-197J. Br Med 1.2. 919-931. Do*ns. T D.. R A Stallones. R.F Frankov-iki e at t I977j Vinyl Chlor.de- Bmh Defects and Fetal Wastage. The Society of Plastic Industries. I9"7 Edmonds. L (I97ei Bmh defects and vinyl chloride. Proceed on Women and the Workplace Conf. fan 17-19th. Washington. DC. pp 114-139 Edmonds. L D,. H Falk and J F Nissirn U97$j Congenita! malformations and vim I chloride. Lancet. 2. 1098 Infante. PF. 11976' Oncogenic and mutagenic risks in communities ith polyvinyl chloride production facilities. Ann NV Acad Sci 2^1.49--5" Infante, P F . J 1C Wagoner. Me Michael et ol (197(i*i Genetic risks of vinyl chloride Lancet. 1. 7 >4-7 35 and 1289-1290. Infante. P.F-. J K Wagoner and R.J Wa**ciler 119"4b> Carcinogenic mutagenic and teratogenic risks associated u-ilh vinyl chloride. Mutation Res . 41. 131 -141 Paddle. C M I I91fci Genetic mk* of vinyl chlor.de. Lancet. 1. 1079 MUTATION RESEARCH 1 Mulatto* Resaareb Lenws publishes considered,dial the results should b Mmafion 8n*tnk Latiwi is aiming . Manuscripts should not be longer the i*bli and illustrations. Ty^atctipt acceptance Contriburioa*--in tnplieaie--may b Acsm** L*tt*n, or directly to the Dr R 1 Preston. Managing Editor P O Bos V. Oak Ridge. TN J7IJ0 Proofs and Reprints Proofreading ** aeccptaflo* of the paper thaaubmi article ineluding the $0 free repnm MUTATION RESEARCH Publication schedule (or IMS - MR is published according to a addition, each section has iu own Reg (green), 'regular' volumes. E Rev (purple). Rest*** in Geneti Mutation Research Letters. Jan. Feb March April Mav June My Aug SP Oct. Nos Dec Total 13 Vols 92- ICJ Reg 92/1+2 93/1 93/2 94/1 94/2 9S/1 95/2 95/3 96y 1 9t 2 96 , J 5 Vds 92-96 The publication schedule of een In particular, an extra volume c AP00018716  United States Health Effects Research Environmental Protection Agency Laboratory Research Triangle Park NC 27711 Research end Development EPA-600/S1-81-057 Sept. 1981 Project Summary ,,^'9 ^ . BARR Association Between Birth Defects and Exposure to Ambient Vinyl Chloride Gilles P. Theriault, Hilda Iturra, and Suzanne Gingras To better define the association between exposure to vinyl chloride monomer (VCM) and ths occurrence of birth defeats, this epidemiological study was made in Shawinigan, Quebec. Canada, where e vinyl chloride polymerization plant has operated since 1943. Birth-defeet rates in Shawinigan during the last 16 years ware compared with rates fen three other communities, and seasonal and spatial variations in Shawinlgan's birth-defect rate* were correlated with estimated VCM concentrations in the environment. Shawinigan had an excess of birth defects which fluctuated seasonally in a way that could correspond to changes in VCM concentration in the environment. Mothers who gave birth to matformad children were younger on average in Shawinigan then in the comparison communities. However, there wee no excess of stillbirths In Shawinigan, the excess in birth defects involved most systems, and variation in birth-defect rates among school districts could not be accounted for by estimates of VCM in ths atmosphere. The occupational and residential histories of parents who gave birth to malformed infants wars compared with those of parents of normal jnfants. The two groups did not differ in occupational exposure or closeness of residence to the vinyl chloride polymerization plant. This Project Summery was devel opedby EPA's Health Effects Research Laboratory. Research Trlangla Park, NC. to announce key findings of the research report that Is fully docu mented In e separata report of the aeme title (see ProjectReportordering information at back). Introduction Vinyl chloride monomer (VCM) is carcinogenic in man and other animals and mutagenic In microbial essays. Drosophila, yeast, mammalian calls, and man. VCM generates mutations primarily through one of its metabolites, chloroethylene oxide, and with the involvement of liver microsomal enzymes. Although miscarriages and fetal losses among the wives of workers exposed to VCM have been studied, such effects remain undocumented. VCM was found in the fetal and maternal blood and the amniotic fluid of pregnant rets after exposure to sir containing VCM; two studies of VCM teratogenicity in animals failed to demonstrate fetal malformations, but showed increased fetal death rates. At normal temperature and pressure, VCM is a gas; it liquifies at -13 C. It Is processed intopolyvinyl chloride (PVC; a plastic] through polymerization reac tions in autoclaves. The gas is released into the environment during unloading, processing, and autoclave-cleaning operations. The concentration of VCM APOOOf8717 io which people in the community ere exposed depends on production rate, wind direction, wind velocity, and distance from the pram. In Shawinigan (population 27,000), a vinyl chloride polymerization plant (owned by B.F. Goodrich Co.. Ltd.) has operated since 1943 and currently produces 25.000 tons/yr of PVC. Ten cases of angiosarcoma of the liver have been reported among workers at this plant, in addition to tha PVC plant, Shawinigan has two chemical plants, one aluminum electrolysis plant one carbide plant, and one pulp and paper mill. A great number of pollutants are discharged into its environment. Fur thermore, prevailing winds tend to blow from the pollution sources towards the town's residential areas. in 1975, a high birth-defect incidence (mostly central nervous system abnor malities) was found in three Ohiotowns with PVC plants. However, two sub sequent studies failed to find any association between birth defects and either work at or proximity of residence to these plants. In a 1977 study, a higher birth-defect rate was found inShawinigan than in Drummondvllle (a town without a PVC plant); the highest rates in Shawinigan were in the vicinity of the plant. The presem study was an attempt to associate this high frequency of birth defects with exposure to VCM. One objective of this study was to establish birth-defect and stillbirth rates in Shawinigan and to compare these rates with those for other communities, in an attempt to confirm the high birthdefect rates previously observed. An other objective was to try to correlate seasonal and spatial variations In the birth-defeet rate with variations in VCM concentration in the environment. The final objective was to compare a group of parents who gave birth to malformed infants with a control group of parents of normal children with respect to residential and occupational history and several birth-defect risk factors. In determining birth-defect rates in Shawinigan. the study included all stillbirths and malformed children born of mothers who resided within the city limits of Shawinigan at the time of delivery and who delivered between January t, 1966. end December 31. 1979. The case-control study was limited to a shorter period (January 1973 to December 31,1979). because it required information based on the mothers* recollection of events during their pregnancies. A birth defect was z defined as i gross physical or anatomic developmental anomaly present at birth or detected at the hospital during the first days after delivery. To assess the importance of the exeess of birth defects In Shawinigan, three comparison communities were chosen, based on their similarity to Shawinigan in population size and structure, socioeconomic level, and medical-care facilities. To take into account the influence of environmental pollution, one town with an aluminum plant but no VCM-emitting plant (BateComeau--Hauterive) and two towns with neither a VCM nor an aluminum plant (Drummondvilla and Rimouski) were chosen as control communities. The Quebec Population Registry provided the annual numbers of births and stillbirths in the communities; as the 1979 data were not available, numbers were estimated from the three preceding years. Birth-defect children and controls were identified and data were collected from several medical files and hospital rosters (delivery-room daybooks, birth-defect rosters, discharge lists, mothers' and children's medical files, and birth rosters). Shewinigan'a 14 school districts were used asthe unit of spatial distribution of birth defects. For the case-control study, the mothers of affected Infantsand matched controls were interviewed at home. Cases end controls were matched by maternal age within two years, sex of tha infant, and place of residence of the mother. Two studies were conducted to assess vinyl chloride concentration in the air in Shawinigan. The first was a study of the feasibility of measuring VCM in the air at several locations in Shawinigan using air sampling and analysis techniques (summarized in an appendix to the report of the present study). Its conclusion was that environ ments! VCM concentrations could be assessed by ambient air sampling atvsrious sites in Shawinigan; depending on location, sampling detected levels up to 45 ppb. During winter, VCM tended to accumulate in the snow in the vicinity of the plant, end VCM concentrations differed between indoor and outdoor samples. The report recommended a continuous one-year sampling program with special attention to meteerologie, topographic, and demographic data to establish the true VCM concentrations to which the Shawinigan population ia exposed. Considering the high cost of such a sampling program, it was decided that for the present study, ambient vinyl chloride concentrations in Shawinigan would ba estimated using a dispersion model based on production records and the results of previous air-monitoring activities. This studywas conducted by a subcontractor. The dispersion model used the Pasquil!-Gifford equation, and its variables included wind direction end velocity, rainfall, humidity, tempera ture, topography, and estimated VCM production and emissions. The model allowed construction of isopleths of estimated vinyl chloride concentration over Shawinigan. Results From January 1966 through Decem ber 1979. there were 4534 live births and 33 stillbirths in Shawinigan. Of tha liva infants. 160 had birth defects, and of the stillbirths, 9 had birth defects. The birth defects reported most frequently were those of the musculoskeletal system, followed by the cardiovascular, central nervous, and urogenital sys tems. Tha ages of the mothers did not differ significantly among the various types of birth defect. Defects of the central nervous system (CNS) were particularly frequent among malformed infanta with abort gestation periods. The yearly numbers of malformed children per 100 births varied from 1.68 (in 1969) io 6.84 (In 1973), with en overall rate of 3.46. Detailed analysis of the monthly distribution of birth defects and the distribution by affected system for the year 1973 showed no tinQle large increase thatcould accountforthe high rate In that year. Nor did the yearly distribution by system show any par ticular feature thatcould aocountforthe annual variation in the overall rates. Furthermore, birth-defect rates did not consistently Increase or decrease with time. The observed number of malformed children in Shawinigan was higher than would be expected based on the rate for each comparison community or for all three comparison communities together (see Table 1). The excess birth defects in Shawinigan occurred in the central nervous, cardiovascular, urogenital, -and musculoskeletal systems, the eye and ear, and the chest. As the types of defects lound in excess in Shawinigan were also the most common types of defects overall, it can be concluded that birth defects in general were in excess in Shawinigan. The proportion of mal formed infanta wasgreater inShawinigan than In the comparison communities in AP00018718 Table 1. Number of Malformed Children Observed in She winigan Compered with Expected Numbers Based on Rates for the Comparison Communities (1966-1979f Affected System Observed in Shawinigan Expected Based on Drummondvitte Expected Based on Baie-Comeau-- Heulerive Expected Based on Rimousfd Expected Based on AH Comparison Communities Centre/ nervous Cardiovascular 30 37 19.69 19.69" 18.18 13.94" 15.33" 43.06 * 17.96* 24.29* Gastrointestinal 11 9.04 9.70 10.96 9.80 Urogenital Musculoskeletal 30 49 19.15* 36.71 13.94" 27.88" 13.14" 40.14 16.72" 34.70* Mouth and upper airways Eye and ear Chest 17 6 3 6.92" 1.06" O.S3* 13.33 1.82 -- 13.14 -- 0.73 10.82 1.02" 0.4 r Syndromes and other defects 6 6.92 9.70 Total 1S9 102.68" 98.80" Ratio of Poisson variable f its expectation (36); * indicates p < 0.06; * indicates p < 0.01. 10.95 124.08" 8.98 107.36" all vears except 1969 and 1972 (see Table 2). The number of stillbirths differed only between Shawinigan and Drummond- villa, where the number of stillbirths was significantly higher. The proportion of malformed children among the still- bom was higher in Shawinigan than in the comparison communities. This is consistent with previous findings of an excess of birth defects in Shawinigan. Mothers who gave birth to malformed children were significantly younger in Shawinigan than in the comparison communities for all malformations oombined and for defects of the CNS, mouth and upper airways, and eye and ear. Children in Shawinigan did not tfffer from those in the comparison communities in mean gestational age at birth, except in the <case of chest malformation, for which the sample size was very small. Figure 1 compares the monthly birth* defect rates for Shawinigan with those for Drummondville and Rimouski. The Shawinigan ourve is V-shaped, with the lowest rates in the summer, whereas the curve for the comparison communlties is flatter. The seasonal variation in birth-defeet rates was statistically significant for Shawinigan, but not for the comparison communities. The spatial distribution of birth defects in Shawinigan with respect to the PVC plant was analyzed; In no Table 2. Distribution of Malformed Children for Each Year (1966-1979) Year Shawinigan Rata1' 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975 1976 1977 1978 1979 Total 16 13 8 6 IS 6 6 18 8 16 13 14 11 to 1S9 3.S4 3.62 2.30 1.68 4.70 2.08 2.19 6.84 2.97 4.40 3.98 4.66 3.33 3.11 3.48 "Number of malformed children per 100 births. indicates p < O.OS. Comparison Communities 31 33 24 27 24 30 34 44 43 SI 36 50 52 47 626 Rates 1.82 1.96 1.61 1.78 1.66 2.06 2.43 3.17 2.81 3.10 2.20 2.76 2.88 2.69 2.35 SH/Compar/son Communities 1.96 1.80 1.62 0.94 2.83* 1.01 0.90 2.16* 1.06 1.42 1.81 1.65 1.16 1.16 1.48* 95% Confidence Interval (1.08, 3.52) (0.96. 3.39) (0.69. 3.34) (0.41. 2.18) (1.55. 5.17) (0.53. 1.94) (0.36. 2.20) (1.28. 3.65) (0.48. 2.33) (0 81. 2.49) (0.93. 3.51) (0.93. 2.93) (0.61. 2.20) (0.60. 2.26) (1.24. 1.75) 3 AP00018719 I previous abortions. Thera was one ptevious stillbirth among the control mothers and none for the case mothers; there was one previous malformed child in each of the two groups. There was no significant difference between cases and controls in the father's age. No mother (case or control) was exposed to X-rays during the first trimester of pregnancy, and only one case mother was exposed during the second third of pregnancy; exposure during the third trimester did not differ significantly between case end control mothers. Table 4 summarizes the mothers' occupations before and during their pregnancies. None of the women were ever exposed lo VCM at work before or during pregnancy. The working experi ences of the case and control mothers before and during pregnancy did not differ, nor did their smoking habits or alcohol consumption. Two mothers of Month of Birth defective infants reported having used the drug LSD before their pregnancies. Figure 1. Monthly distribution of birth-defect rotes. There was no significant difference between cases and controls in the father's occupational exposure to school district did the ratio of observed not differ significantly, nor was there a chemicals, and no fathers were ever to expected number of birth defects differ significantly from 1. The four districts with the highest rates are significant difference between case and Control mothers In number of previous pregnancies. exposed to vinyl chloride (see Table 6). The distance between each mother's place of residence and the VCM plant located on the north-south axis passing through the vinyl chloride plant; the Mothers of malformed infanta reported no excess of diseases during pregnancy; was measured to 100 m. using a map of the city; there was no significant district in which the plant is located had about the expected number of birth however, the following diseases sus pected to bear a high risk of birth defect difference between the two groups in distance from the VCM plant. defects. The yearly average concentra tion of vinyl chloride was estimated for each school district based on data from were reported more frequently by case than by control mothers: rubella, hydramnios, epilepsy, nonpsychotic Discussion Some observations of this study a study entitled "Dispersion Patterns of mental disorders, and psychosis. There support the existence of an association Vinyl Chloride Emitted by B.F. Goodrich CO., Ltd., Shawinigan, Qua/' (which is was no significant difference between esse and control mothers in number of between VCM in the sir and birth defects in the exposed community. appended to the report of the present study). Birth-defect rates did not differ between school districts with high and low VCM exposure, either for all birth Table 3. Comparison of Tata! Birth Defects* anti CNS Birth Defects* Between School Districts with High and Low Atmospheric Vinyl Chloride Concentretion defects or for CNS defects (see Table 3). Likewise, school districts adjacent to the plant did not differ from the other school districts in numbers of birth defects (total or CNS>. nor did districts Births with defects School Districts With High VCM Levels'6 87 School Districts With Low VCM Levels 70 Total rs7 differ within and beyond a one-mila radius of the vinyl chloride plant. For the period January 1973 to Births without defects 2285 2125 4410 December 1979. 68 cases of birth defects were identified in Shawinigan and matched withcontrols(42 male end 26 female pairs). Five of the cases were Stillborn; ail of the controls wore born Births with CNS defects Births without CNS defects 16 2356 13 2182 29 4538 alive. There was nosignificantdifference Total births 2372 2195 4567 between cases and controls in number of weeks' gestation at delivery. The frequencies of previous birth defects in X\ = 0.80; p> 0.3S. Mf*, = 0.10; p> 0.70. the families of eases and controls did ^School districts nos. 1,3. 5, 6. 7. and 8. 4 AP00018720 Table 4. Distribution of Coses end Controls by Mother's Occupation* There was no difference in occupa Mother's Occupation Cases Before During Pregnancy Pregnancy Control Before During Pregnancy Pregnancy tional or residential history between the parents who gave birth to malformed infanta and the control parents. Both groups resided at similar distances from Work outside home Without the plant, and none of the parents had exposure to chemicals 41 22 42 20 worked at the plant. Furthermore, all types of birth defects were in excess in Work in VCM industry 0 0 0 0 Shawinigan, rather than those of any Work outside home with exposure to chemicals 2 1 2 particular system. These results agree 1 with those for the three Ohio cities; however, agents known to beteratogenic Stay at home Totai 25 45 24 47 in humans and experimental animals have very specific effects, and it seems 63 63 68 68 unlikely that any agent would produce ) ^Partitioning stay at home vs. work outside home before pregnancy: X*t = 0.03; p">0.8S. Partitioning stay at home vs. work outsidehome duringpregnancy: the variety of malformations found In excess in Shawinigan. X*x*0.13;p>0.71. Possible explanations ol the results as artifactuai are not convincing. It is while others tend to contradict such an association. High birth-defect rates in Shawinigan were confirmed for a 16yeer period, and women who gave birth to malformed children were, on average, younger in Shawinigan than in the comparison communities. These resuits are consistent with previous findings for three Ohio towns with PVC plants. The present study revealed seasonal variation in birth-defect rates that could correspond to variation in atmospheric VCM concentrations. VCM could not be measured in air samples during Decem ber, January, and February. It is believed that during these months, VCM tends to accumulate near the plant as a liquid, because the outdoortemperature Is below its liquefaction point; this VCM would be released into the air in the spring. Birth-defect rate# were lowest in September, which is eight months after midwinter, corresponding to the time between the first third of pregnancyand delivery. This observation would tend to support an association between VCM concentration in the air and birth defects in the community. One con sultant believed that below its liquefac tion point, VCM would remain in the air in droplets, at s concentration similar to that found at higher temperatures. However, because people spend more time indoors during the winter than the rest of the year, winter exposure would tend to be low in any case. On the other hand, several observa tions of the present study tend to argue against any association between VCM concentration in the air and birth defects in the community. The spatial distribution of birth defects in Shawinigan cannot be explained on the basis of estimates of VCM concentrations in the community. Malformation rates were not relatively high either near the plant or in theeras where VCM concentrations were estimated to be highest, and the school district with the highest birthdefect rate was far from the plant. However, VCM concentrations were not measured directly, but estimated by a. theoretical dispersion model based on approximate production and emission values, because the B.F. Goodrich Co. would not release the actual values. unlikely that Shawinigan's physicians were'more inclined to diagnose birth defects than were physicians in the comparison communities. Birth defects were included In this study on the basis of their obviousness, and the birthdefect rates were the same in the three comparison communities. Furthermore, for severe birth defects- like those of the CNS. which cannot be misdiagnosed, rates were much higher in Shewinigan than in any of the comparison com munities. The method by which thedata were collected made it very unlikelythat a bias in the quality of the information from the archives of the regional hospitals could have influenced the results. The possibility remains that pregnant mothers residing outside ofShawinigan who were at risk of having a malformed child migrated to the city for delivery, thereby Increasing the birth-defect rate for that town. In the case-control study, six mothers (6.7%) were rejected because they had moved to the city of Shawinigan after the first third of pregnancy, and four more cases were untracaable. Thus, as many as 1 f % of Table 5. Distribution of Cases snd Controls by Father's Occupation* the birth-defect cases observed in Shawinigan might actually have come Father's Occupation_____________ Ever worked in vinyl chloride industry Casas 0 Controls 0 from elsewhere, reducing the number of observed cases to 142. However, birth-defect rates would still be sig nificantly higher than in thecomparison Ever worked in industries with exposure tochemicals 20 communities, leading us to believe that 25 the excess noted in Shawinigan was real. Never worked in industries Animal studies have shown that with exposure to chemiceis 43 39 exposure to high levels of VCM during Unknown 5 pregnancy results more often in high 4 rates of fetal loss and miscarriage than Total *X3, = 0.73; p > 0.39. 68 68 in birth defects. However, stillbirth rates were no higher in Shawinigan than in the comparison communities, and in the 5 APOOO18721 case-control study, abortion rates were not higher for case than for control mothers. Several industries in Shawinigan emit pollutants into the atmosphere, and several of the pollutants may interact to generate potent mutagenic or teratogenic chemicals in the com munity. The analysis of such an envi ronment and its association with the excess of birth defects was beyond the scope of the present study. However, in the case-control study, there was no difference between the numbers of case and control parents who worked at the aluminum plant, and tha comparison community with an aluminum elec trolysis plant (Baie-Comeau--Hauterive) had lower birth-defect rates than did Shawinigan. Thus, the aluminum in dustry probably was not solely respon sible for the excess of birth defects In Shawinigan. Among risk factors {other than occu pational or environmental exposure to a pollutant) known to be associated with birth defects, epilepsy and mental disorders before and during pregnancy and the use of the drug LSD before pregnancy were reported more fre quently by mothers of malformed children than by control mothers. Drugs prescribed to control epilepsy have been reported to be associated with birth defects and could account for a few birth defects observed In Shawinigan, as could LSD. No other risk factor was reported more frequently by the case than by the control mothers. An association between VCM in the air and birth defects in the exposed community eennot be substantiated st the present time. If the association exists, it cannot be measured by the methods used in this and in previous studies or in populations of the sizes studied so far. Conclusions The conclusions of this study can be summarized as follows: 1. For the years 1966 through 1979, there was an excess of birth defects in the population of Shawinigan. Quebec. This result is similar to the findings for several U.S. cities where vinyl polymerization plants operate. 2. Birth-dafect rates underwent a seasonal variation that could cor respond to variation in the con centration of VCM in ambient air. 3. Mothers from Shawinigan who gave birth to malformed infants 6 were younger than mothers from the comparison communities who also gave birth to malformed infants. 4. The excess malformations involved not only the central nervous system, but almost ali body sys tems. 5. No correlation was found between the spatial distribution of birth defects in the town and estimates of VCM concentrations in the air. (These estimates were based on approximate data, since informa tion on RVC production and VCM emissions was not available.) 6. Occupational exposure as a causal agent was ruled out, because none of the parents in the study had ever worked at the VCM plant. 7. Cases and controls did not differ in distance of residence from the plant. 8. No excess of stillbirths was ob served in Shawinigan, and abortion rates were no higher for mothers of malformed infants than for mothers of normal infants. Some observations of this study support an association between VCM in the air and birth defects in the exposed community, while others tend to indi cate that no such association exists. As the present results are inconclusive, the possibility that VCM generates birth defects in human communities requires further consideration. This would best be accomplished through a program during the next five to ten years to monitor VCM concentration in the air and birth defacts in the exposed communities. Gilles P. Theriault. Hilda Hurra, andSuzanne Gingras are with the Department of Social and Preventive Medicine, faculty of Medicine, Laval University, Ste-Foy, Quebec. Canada G1K 7P4. Jeff Baaubier and Gregg Wilkinson are the PA Project Officers (see below). The complete report, entitled "AssociationBetweanBirthDefoctsandExposurm ro Ambient Vinyl Chloride." fOrder No. PB St 238 883: Cost: $ 11.00, subject to change) will be available only from: National Technical Information Service B28S Port Royal Road Springfield. VA 22161 Telephone: 703-487*4650 The EPA Project Officers can be contacted at: Health Effects Research Laboratory U.S. Environmental Protection Agency Research Triangle Park. NC 27711 O US GOVERNMENT PRINT!NO OffICE, !9tt - 787-012 '7327 AP00018722