Document EvJj85179O0j3ZXeyQOo4ZdOx

RECEIVED AU3 1 0 1983 TERATOLOGY 2? 359-370 19S3 Evaluation of the Association Between Birth Defects and Exposure to Ambient Vinyl Chloride GILLES THERIAULT HILDA ITURRA wd SUZANNE GINGRAS Department nt'Sociai anil Preventive Medicine Faculty of Medicine, Laval Sie-Foi Quebec Canaan C/A' TP4 ABSTRACT Birth defects incidence for infants born to residents of Shawimgan. Canada in 1966-1979 were significantly higher than in three compar ison communities Since there has been a vinyl chloride polymerization plant in this town since 1943 from which ten cases of angiosarcoma of the liver have been identified, this study explores the possible association between exposure to vinyl chloride monomer CVCM) in ambient air and the occurrence of birth defects in the community. The excess of birth defects fluctuated seasonally in a way that corresponded to changes in VCM concentration in the environment. Mothers who gave birth to malformed children were younger on average in Shawimgan than in the comparison communities. However, there was no excess of still-births in Shawmigan. The excess in birth defects involved most organ systems, and variation m birth-defect rates among school districts could not be accounted for by estimates of VCM in the atmosphere. The occupational and residential histories of parents who gave birth to malformed infants were compared with those of parents of normal infants. The two groups did not differ in occupational exposure or closeness of residence to the vinyl chloride polymerization plant. Some descriptive data from this study raised the hypoth esis of an association between VCM in the air and birth defects in the exposed community, but as a whole, within the sample size available, such an associa tion could not be substantiated. Vinyl chloride monomer (VCM) is carcino genic in animals (Viola et al., '71; Maltoni and Lefemine, '74,'75) and man (Creech and Johnson, '74; Thomas and Popper, 75; Makk et al.. 76; Delorme and Thdriault, 78; Monson et al., 74; Waxweiler et al., 76). It is mutagenic in man: Chromosome breaks have been observed in lymphocytes of workers ex posed to VCM (Funes-Cravioto et al., 75; Ducatman et al., 75; Fleig and Thiess, 78; Leonard et al., 77; Hansteen et al., 78; Kucerova et al., 79), in microbial tests, in Dro sophila, in yeast, and in mammalian cells (Drevon and Kuroki, 79; Bartsch and Montesano, 75; Loprieno et al,, 76; Magnusson and Ramel, 76). VCM generates mutations primarily through one of its metabolites, chioroethylene oxide, and with the involve ment of liver microsomal enzymes (Bartsch and Montesano, 75; Vainio, 78; Rannug et al., 74; Green and Hathway, 78). Although miscarriages and fetal losses among the wives of exposed workers have been sus pected (Infante et al., 76), such an effect re mains undocumented (MacMahon, 77; Downs et al., 77). VCM teratogenicity has yet to be documented. VCM was present in the fetal and maternal blood and the amniotic fluid of pregnant rats after exposure to contaminated air (Ungvary et al., 78). Two studies of VCM teratogenicity in animals (Ungvary et al., 78; John et al., 77) failed to demonstrate fetal malformations but showed increased fetal mortality rates. . VCM mutagenicity and possible teratogen icity in man raised the question of the origin of birth defects in communities near VCMemitting plants. At normal temperature and pressure, VCM is a gas; it liquifies at -13C. It is processed Received April 8. 1982, accepted December 1. 1982 Addreaa reprint requests to Gill** P Theriault, Institute of Occupational Health end Safety, McGill University. 1130 Pine Avenue-West, Montreal. Quebec H3A 1A3 t 1983 ALAN R. USS. INC- 360 C THERIAULT. H ITURRA, AND S GINGRaS into polyvinyl chloride (PCV, a plastic) through polymerization reactions in auto claves. The gas is released into the environ ment during unloading, processing, and autoclave-cleaning operations. The concen tration of VCM to which people m the community are exposed depends on production rate, wind direction, wind velocity, and dis tance from the plant. In Shawmigan (population 27,000), a vinyl chloride polymerization plant has been m op eration since 1943 The piant, which employs about 250 workers, currently produces 25,000 tonsyear of PCV. Ten cases of angiosarcoma of the liver have been reported among work ers at this plant. In addition, Shawmigan has two other chemical plants, one aluminum electrolysis plant, one carbide plant, and one pulp and paper mill Several pollutants are discharged into the environment. This study pursues four objectives. First, to compare the birth-defect and stillbirth rates m Shawmigan with other communities in an attempt to document the high birth-defect rates previously observed in this town; sec ond, to correlate monthly and seasonal vari ations of birth defects with concentration of VCM in the environment; third, to correlate geographic variation in birth-defect rates with estimates of VCM in the air in the sev eral residential areas; and finally, to com pare a group of parents who gave birth to malformed infants with a control group with respect to residential and occupational his tory, as well as exposure to other risk factors known to generate birth defects. METHODS Study population and observation periods For the assessment of birth-defect rates, the population comprised all women who de livered during the study period and whose residence was within the city limits of the study or the comparison communities at the time of delivery. It extended from January 1, 1966. to December 31,1979. The starting year 1966 was selected because, due to hospital reorganizations, the information was unob tainable in a suitable form prior to that date. The case-control study was limited to a shorter period (January 1,1973, to December 31, 1979) because it required information based on the mothers' recollection of events during their pregnancies. It included only Shawmigan mothers who gave birth to a malformed child and their controls. Definition of a birth defect A birth defect was defined as a gross phys ical anomaly present at birth or detected at the hospital during the first days after deliv ery jwithin the first 4-6 days) A list of birth defects to be included in the study was drawn beforehand and only those that fit tms list were retained. Two major difficulties were encountered. In birth defects of the cardiovascular system, it soon became apparent that in several hos pitals. no diagnoses other than murmurs of the heart were reported, whereas in other hospitals ie.g., Shawmigan), thorough inves tigations were conducted, leading to precise diagnoses. Consequently only heart mur murs judged severe enough were included in the study, under a separate category Sever ity and significance of heart murmurs were assessed by consulting the children's subse quent medical records. Although such minor defects as metatarsus varus, calcaneum varus and valgus, metatar sus adductus, and abnormal positioning of fingers or toes were not included in the study, foot anomalies which required either a cast or surgery for correction in the year follow ing birth, were considered defects. Comparison communities To assess the importance of the excess of birth defects in Shawinigan. three compari son communities were chosen, based on their similarity to Shawinigan in population size and structure, socioeconomic level, and medlcal-care facilities (Table 1). In order to take into account the influence of environmental pollution, one town with an aluminum plant but no VCM-emitting plant (Baie-ComeauHauterive) and two towns with neither a VCM nor an aluminum plant (Drummondville and Rimouski) were chosen as control communities. The recourse to referent com munities was necessary because no accurate national or provincial data were available. Data sources - 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 3 preceding years. The Quebec Ministry of Social Affairs provided a list of hospitals where women residing in these communities gave birth during the study period. The School Board of Shawmigan furnished the 1 7 _3 P? 3(CX>l <a Arr of the first study, ambient VCM concentra- li.nrroinr.ili \ [nilrf iv<? 12 1 10 f)0 5 87 0 10HM I 1,200 IH 8 ft 2 s 3 I -P P p to - 2 P ft 'cwr --n<w0!i 3o 3 nd>> o1-1 ci r K; ^<T5 ro p pd^ C3L 0 Jd 1 32 '~ nrr o03- r-h rt) P- n cr d 3m . 3^-m "ow^a _ p oa> to Cl nP-- 2(oa'!-<L HiSq "S 2 pd 3 o* 12 ra 3opa nC>- 3 cl ft 8 S.S =?3 o rn 3s jrge ^i rc fij CfD=L ,,3 3 T- 0O3- ~ff7> 3r 8-- C>m--L 3 a g2 g ^sj 0t_o> CO 3 r+ n O- Cl ?r\ CJ tpd O - 5- ft n? cr T -E P_2--5fpct-.i SrPo-j " " 3 OP- "cr o 2 35 -- 3-`d3i a tPnHf*/o0jI >Xo' Cj Xr' o;c 5m Scrcrq p PP p "pg D- ^ cr a> -3 ; 3 W CX [ s a,; 33 23 H<t> Jcrocr ^c1d o'1" t (B '' 5. 2 ! pPC r&StT- 5CT 3524? c!*Co rr*r ^ex s.S-3! re S *1:1S' rt a (J rf, m-< 5f a o3 n3> <' 6! B^ --SPan- n$*p-*j B 1 \ s ; <j> < "C | ^ -rHa ^5o 6Om c g8S|? a o (Z & a HHa g. "*Rd* P n8 00; &tn C CO ? * 0 jL *-f _ '01_. c 'T"'mi 0-^3 & " i 8$frig? ^&s\ ! B<: ^ST g w5 5B R'<5 o ^ s-j 3 O ex 3(0 W {C*L.T2O S>JJ.S-~S. SS^sE s-o <3 !r o _ '< -SoS-S fttr oO- Cw Q.H3 w r, a S n i3 3 , &58 2 "2,^ _< "t ft ET, O 3S ^3553 *2, P-- XW 3 {f* Xp> O HPp tr P $ S5 2 ? v1* 3 tO on cn I'Attl.F. 2. Di^tr tbulitm of tualftH'iin'ti children h\ sri ntttl tiffet tfil sy^fitn (Shtmonipaif, /.90f /97'0 AfTerlcd system Muirs N H:ltp' I'rmnlrH N li.llc' i.iL.i (Vnlrnl nri vous C'm dm vascular (nslrninlrslinnl llrnjjrmtnl Musculoskeletal MrmLh nml uppci airways Eye anil ear Clii-sl Symhomrs and other defer! s Tola! mimlri nf inalfonnctl children n f) 57 17 7 73 21 !) 0(1 10 7 27 7 :i oo 1 i H2 28 12 00 2 E> Oi 18 7 71 31 1 1 09 G 2 57 11 5 00 1 1 71 2 (1 ill | a i.i 2 0 !>l 1 0 '13 5 2 27 AS 30 12 74 33 fil 10 17 11 30 19 17 (> 3 0 1 79 'NmiiiIm r of iiinlftinin'd rhddrwi pci I 000 l<< r hnf lut p < nooi CO O) to V 0 51 0 21 0 30 19 M 1 73 1 20 0 11 0 00 1 09 0 IH H X t** 2 > c H X H P3 33 > v: o t/> o v o 33 > tn TABLE 3 Number of matfor med children absented m iiftnn t {import'd with expected nuni/jri1 s fas the <i)/ja/>tiri^n itit*.frHtfi r)791 TAfli-fi J. Number of ma ffarmed ehthiren observed in S/tawtntgan compared with expected numbers for the compcu >1 so a auttmtu tifustWUh }')7`U I Affected system Central nervnus Cardiovoscular GaatrointcsUnal Urogenital Musculoskeletal Mouth and upper airways Eye and ear Cheat Syndromes and oilier defects Total nmutter of malformed children Observed m Shawmigu n 30 37 11 30 49 17 6 3 6 159 Expected bused on Drunirnomlv die 19 69* 19 69** 0 04 19 15* 36 71 6 92** 1 06* * 0 53* f> t)2 102 68** Ex peeled bn^erl on It,lie Haulerive 18 18* not** 9 70 i;i or* 27 88** 13 33 l 82* 0 70 oa bo** l,xp> Mr.l bositl on Itmuni^k i is.} r i i Ob JO 9'i n ir* 10 14 13 M 0 i.) 10 90 124 OH* * ] ,X|K c led based Oil all com panstui cnnmumities '--I - " - i 1 9b* 21 29* 9 80 15 72* * 34 70* 10 82 1 02* * Oil* 8 98 107 16 * * *P < 005 **P < 001 Is 8 s h it >3-0 -33-S0- ES?;^ tw U S s.a <* 2IEiT "n^E S"0 3 ~ ."e Sp 'j*- sa$ ff o- E ~ ?3. sBr&i S 2 cf *< g-a: S. a go itfl o tg^|o3 cn *< **> g-8 <r s^a-i 2- Cfn re ^r - D- 4 O X^CTQ 5 D> EC S5S 5o cr < re P o 2 SC ^ D J2 ^ 3 J2 3 Is *3 8-S-I& $3 iw Q i/1 9 C 3 5 S3t {U X) Og gJ ifc5-3SPErer - SIS C+L wO (D f3 5 <Wt> 3 a % S'8 8g3 CEftTf-J<g5-tSOa B.1 S# ^fk> t-- Ccu g/? 5 w^ S -S 3 2 T3 ^p da> Ca ^C o<> tCnl & to -cL gSw w^CSiL f+ (D tf" F--, l E?< 6" <\ O W ET . C re t/i 9- ^^JO9p. (3rt>) rt> CT *1^0 re Cl 2*eeLrg* t/J '-< >-* ? sp: ?rt>* (i) la "3-- - TOH Co 3 CL. re 5 5t re re 2 :; n3 <P3r .Er'S 5 } <T> 3 ^ c3c c3c n3> iQ-ia cr ^ o .! 3 3'c =r p, 3 - cj 5Qf.pt-Ln n ^^ 33 VI l3-< w1 3^ (k-x Q- ro+> *" on c citr ?rer -w --r- --* -- 3 (!) '-O 93 . *7 9 53 Qj 3 o3 P, p Ho5 0J 0) o CJI ,- --.j f3ii- cr d'*1 CD ^ CMA 0 0 6 1 9 8 Sii 364 G THERIAULT, H HURRA, AND S GINGRaS Year 1966 196? 196c 1969 1970 1971 1972 1973 1974 1975 1976 1977 197S 1979 table 4 Year v distribution nf ma 'furled children I196K- 1979: Shawinigan Rate1 Comparison communities Rale SH Comparison communities 16 13 ' 6 15 5 6 Is 8 15 13 14 11 10 3 54 3 52 2 30 1 6S 4 70 2 06 2 19 h .-`4 2 97 4 40 3 9S 4 56 3 33 3 11 31 1 82 33 1 96 24 ! 5 1 ? 1 7a 24 1 66 30 2 05 34 2 4 3 44 3 17 43 2 SI 51 J 10 36 2 20 50 2 76 52 2 68 47 2 69 1 95: . 52 0 94 2 9 3' 1 01 'j 90 2 16* 06 1 42 1 81 1 65 1 16 1 16 Total 159 3 48 'Number nf malformed children per 100 births 'P < 005 526 2.35 1 46' 95^ Confidence inlrrvdl 3 52, `0 96 3 39 '0 3 34. I. 2 ' 1 55 5 17. 'U 5,, 1 94' (0 ,.ih _ jo. i im 1 65 U is 2 53 .0 81 2 19' <0 ^ 3 51' I- y i 2 y:j, <0 61,2 201 i(j 60. 2 26' d 24 1 75' TABLE 5 Numbers of stillbirths, with and without birth defects, and numbers expected m Shawimgan hosed on rates in the comparison communities Condition With birth defects Number of stillbirths Without birth defects Tout Total number of births Observed in Shawinigan Observed in Drummondville Expected based on Drummondville Observed m Baie-Comeau- Hauterive Expected based on Baie-Comeau-Hauterive Observed in Rimouski Expected based on Rimouski Expected based on all comparison communities 9 15 7,98 7 4.24 5 3 65' 5.51 24 83 44.16" 63 38.18* 44 32.12 38.78 33 ' 4567 98 6584 52 14** 70 7535 42 42 49 35 77 _ 6257 44.29 - mP < QOS mmP< 001 defects (Table 6). Likewise, school districts adjacent to the plant did not differ from the other school districts in numbers of birth de fects (total or CNS), nor did districts differ within and beyond a 1-mile radius of the VCM plant. Case-control study For the period January 1973 to December 1979. sixty-eight cases of birth defects were identified in Shawinigan and matched with controls (42 male and 26 female pairs). Five of the cases were stillborn; all of the controls were born alive. There was no significant difference between cases and controls in number of weeks' gestation at delivery. The frequencies of previous birth defects in the families of cases and controls did not differ significantly, nor was there a significant dif ference between case and control mothers in number of previous pregnancies. Mothers of malformed infants reported no excess of diseases during pregnancy; how ever, the following diseases suspected to bear a high risk of birth defect were reported by cases only; rubella, hvdramnios, epilepsy, nonpsychotic mental disorders, and psy chosis (Table 7). Among the mothers of mal formed infants, five reported previous occurrences of epilepsy, mental disorders, or both. Their children showed the following birth defects; two cases of hypospadias, one of congenital cataract, one of Down's syn drome, and one interventricular septal de ! TABLE Births 1 3irth? i Total birt x ? - 0 60 C* * 0 10 fect. Tv reported their preg There tween cas previous previous ers and n. one prew two grot, ence bet er s age exposed of pregn exposed nancy; TABLE 6 Comparison of total birth defeats1 and CXS birth defeatr1 betieeen school districts u ilh high ana loot atmospheric rim chloride concentration Births with defects Births without defects Births with CN5 defects Births without CNS defects School districts with hig-h VCM level? 87 2,285 16 2,356 School districts with low VCM levels 70 2.125 13 2.1S2 Total 157 4.410 29 4,538 Total births 0 80 P > 0 35 ! 0 10, P ? 0 70 2.372 2,195 4,567 feet. Two mothers of defective infants reported having used the drug LSD before their pregnancies. There was no significant difference be tween case and control mothers in number of previous abortions reported. There was-one previous stillbirth among the control moth ers and none for the case mothers; there was one previous malformed child in each of the two groups. There was no significant differ ence between cases and controls in the fath er'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 preg nancy; exposure during the third trimester did not differ significantly between case and control mothers. Table 8 summarizes the mothers' occupa tions before and during their pregnancies. None of the women was ever exposed to VCM at work before or during pregnancy. The working experiences of the case and control mothers before and during pregnancy did not differ, nor did their smoking habits or alcohol consumption. There was no significant differ ence between cases and controls in the fath er's occupational exposure to chemicals, and no fathers were ever exposed to vinyl chlo ride (Table 9). The distance between each mother's place of residence during the first trimester of pregnancy and the VCM plant CMA 006200 366 G THERIAULT. H ITURRA AND S GINGRaS TABLE 7 Distribution of cases and control by diseases of the mother* during pregnant Disease Cases None Bleeding at the beginning of the pregnancy Ht peru?nsion Rubella Litrwasib of tne gall bladder Ronal calculus Psychosis Premature labor Phiebms H\ drammos Obesity Placenta praevta Epilepsy Nonpsvchotic mental disorders Wound Infectious or parasitic disease Other diseases of the mother 44 6 3 i i i 2 1 2 0 0 1 2 0 4 3 Total for diseases 24 Unknown 0 Total `Partitioning diseases vs no disease, * 0.54. P > 0 45 68 Controls 4S .3 6 0 1 0 0 1 0 0 3 1 0 0 1 6 2 20 0 68 TABLES Distribution o f co<<' and controls by mother's occupation1 Mother's occupation Before pregnancy Cases During pregnancy Control Before pregnancy During pregnancy Work outside home without exposure to chemicals 41 22 42 20 Work :n VCM industry 0 0 0 0 Work outside home with exposure to chemicals 2 1 2I Stav at home 25 45 24 47 Total 68 68 68 6S `Partitioning stav at home v* worn outside home before pregnancy x? " 0 03, P > 0 85. pardoning stay at home vs work outside home during pregnancy, y? 0 13; P > 0,71 TABLE 9. Distribution of coses and controls by father's occupation} Father's occupation Cases Ever worked in vinyl chlond* industry Ever worked in industries with exposure to chemicals Never worked in industries with exposur*ao chemicals Unknown Total -0 20 43 5 68 M * 0 73; A > 0.39. Controls 0 25 39 4 68 was mea.( the city, bj^teen 1 \^Bpla Excess the vicin plants at these b: cnioride first des(Infante, tween 1 birth to the inde of the t mostly t per alir clubfoot In an Center birth de et al. (" for one piant, b aly am Paines' study, r fected i the tw Paines' trol mo of the l Anot sized f women plants, were g' were c among method In a r tries, M evident genera* heavily be reg' and t avails Dowm methc conclu cated BIRTH DEFECTS AND VINYL CHLORIDE 367 was measured to - 100 m, using a map of the city, there was no significant difference between the two groups in distance from the VCM plant. " DISCUSSION Previous studies Excess of birth defects in communities in the vicinity of vinyl chloride polymerization plants and the possible association between tnese birth defects and emissions of vinyl chloride monomer into the atmosphere were first described for three Ohio communities (Infante, 76) The excess was constant be tween 1970 and 1973, Mothers who gave birth to malformed children were younger in the index communities than in the balance of the three counties. The excess involved mostly the central nervous system (CNS), up per alimentary tract, genital organs, and clubfoot. In analyzing data collected through the Center for Disease Control's hospital-based birth defects monitoring program, Edmonds et al. (75) found no increase in CNS defects for one city in Pennsylvania with a PVC plant, but confirmed the excess of anencephaly and spina bifida previously noted in Painesville, Ohio. However, in a case-control study, none of the interviewed parents of af fected infants had ever worked at either of the two PVC polymerization plants in Painesville, whereas two fathers of controls had; none of the parents in either group lived within two miles of either plant. Further more, a significantly larger proportion of con trol mothers worked within a 10-mile radius of the PVC plant. Another study (Infante et al., 76) empha sized fetal losses and miscarriages among women whose husbands worked at PVC plants. Although it concluded that fetal losses were greater among women whose husbands were occupationally exposed to VCM than among controls, this study was criticized for methodological weaknesses. In a report to the Society of Plastics Indus tries, MacMahon (77) concluded that the only evidence so far was to the effect that VCM generates chromosome breakages in workers heavily exposed to it, but that VCM should be regarded as a potential human mutagen and teratogen until better evidence was available. In another report to the Society, Downs et al. (77) criticized the statistical methods used in vinyl chloride studies and concluded that the existing evidence indi cated associations between (1) VCM exposure and lymphocyte aberrations in workers and (2) VCM exposure of workers and fecal was tage among the workers' wives. Those au thors found no evidence for an association between VCM exposure and birth defects, but cautioned that such associations may not have been detectable by methods available at the time and that monitoring should con tinue. A high incidence of CNS birth defects was found in Kanawha County, West Virginia, from 1970 to 1974 (Edmonds et al., 78). As there is a polyvinyl chloride plant in Kana wha County, a possible relationship between CNS defects and parental exposure to VCM was investigated. In a case-control study, no relationship was found between birth defects and parental occupation. Although the pat tern of case-family residences tended to differ from that of controls, it did not correlate with local wmd direction and air pollution. The present study Some descriptive data from this study raised the hypothesis of an association be tween VCM in the air and birth defects in the exposed community, but as a whole, within the sampl^ size available, such an association could not be substantiated. Birthdefect rates in Shawmigan were high for the 15-year period, and women who gave birth to malformed children were, on average, younger in Shawmigan than in the compari son communities. These results are consist ent with previous findings for three Ohio towns with PVC plants (Infante, 76). The seasonal variation in birth-defect rates corresponded to variation in atmospheric VCM concentration. No VCM was found in air samples during December, January, and February. It is believed that during these months. VCM tends to accumulate near the plant as a liquid, because the outdoor tem perature is below its liquefaction point. This VCM would be released into the air in the spring. Birth-defect rates were lowest in Sep tember, which is 8 months after midwinter, corresponding to the time between the first third of pregnancy and delivery. These obser vations favor an association between VCM concentration in the air and birth defects in the community. On the other hand, several observations of the present study tend to argue against any association between VCM concentration in the air and birth defects in the community. The geographical distribution of birth defects in Shawimgan was not correlated with esti- 36S G THERIAULT. H ITL'RRa, AND S GINGRaS mates of VCM concentrations in the commu- communities, leading us to believe that the mt\. Malformation rates were not relatively excess noted in Shawmigan was real. high either near the plant or in the area Animal studies have shown that exposure w here VCM concentrations were estimated to high levels of VCM during pregnancy re lo he highest, and the ^school district with the sulted more often m high rates of fetal loss higrtest birth-defect rate was far from the and miscarriage than in birth defects piant. fUngvary et al . '78, John et al., '77- How There was no difference m occupational or residential history between the parents who gave birtn to malformed infants and the con ever. stillbirth rates were no higher in Shaw migan than in the comparison communities, and in the case-control study, abortion rates trols Bom groups resided at similar dis reported were not higher for case than for tance; from the piant. and none of the parents had worked at the plant. Further more. all types of birth defects were in excess in Shawmigan These results agree with those for the three Ohio cities; however, agents known to be teratogenic in humans and experimental animals have very' specific control mothers. Several industries m Shawmigan emit pol lutants into the atmosphere and several of the pollutants may interact to generate po tent mutagenic or teratogenic chemicals in the community. A thorough analysis of such an environment and its association with the effects, and it seems unlikely that any agent would produce the variety of malformations found m excess in Shawinigan. excess of birth defects was beyond the scope of the present study. However, in the casecontrol study, there was no difference be Possible explanations of the results as ar- tween the numbers of case and control par tifactual are not convincing. It is unlikely ents who worked at the aluminum plant, and that Shawmigan's physicians were more in the comparison community with an alumi clined to diagnose birth defects than were num electrolysis plant (Baie-Comeau-Hau- physicians in the comparison communities terive) had lower birth-defect rates than did since they did not know about such an asso Shawmigan. Thus, the aluminum industry ciation when the diagnoses were made (ex probably was not responsible for the excess I cept m 1979, where no difference was seen of birth defects in Shawinigan. from previous years). Birth defects were in Among risk factors (other than occupa cluded in this study on the basis of their tional or environmental exposure to a pollu obviousness, and the birth-defect rates were tant) known to be associated with birth the same in the three comparison communi defects, epilepsy and mental disorders before ties. Furthermore, for severe birth defects and during pregnancy and the use of the like those of the CNS, which cannot be mis drug LSD before pregnancy were reported diagnosed, rates were higher in Shawmigan more frequently by mothers of malformed than m any of the comparison communities. children than by control mothers. Drugs pre The method by which the data were collected scribed to control epilepsy have been re was the same everywhere It is very unlikely ported to be associated with birth defects that a bias in the quality of the information (Smithells, '76) and could account for a few from the archives of the regional hospitals birth defects observed in Shawinigan, as could have influenced the results. could LSD. These differences, however, could The possibility remains that pregnant be due to a recall bias whereby the mothers mothers residing outside Shawimgan, who were at nsk of having a malformed child, migrated to the city for delivery, thereby in of malformed infants were more aware of exposure to possible etiologic agents during their pregnancy than the mothers of normal creasing the birth-defect rate for that town. children. In the case-control study, six mothers (6,7%) were rejected because they had moved to the city of Shawmigan after the first third of pregnancy, and- four more cases were untraceabie. Thus, as many as 11% of the birthdefect cases observed in Shawinigan might -In the present study, we were unable to substantiate the presence of an association between VCM in the air and birth defects in the exposed community. In view of the high numbers of angiosarcoma of the liver ob served among production workers and the actually have come from elsewhere, reducing possible large emissions of VCM, it can mean the number of observed cases to 142. How that such an association does not exist. It can ever. birth-defect rates would still be signifi also be the result of a small number of obser cantly higher than in the comparison vations. The probability of finding an excess ( * of birth o- This re*, of contract or Social University En\ ii onm tent ha = n repoit pu Printing C The aut Kempf. D and Jeff I tection A and assist Bailar, J C., the ratio < metrics. 2< Banach. H carcinoger 32 93-H3 Creech, J.L. of liver u Occup. M< Delorme. F sarcoma c Med, 20,: Downs, T,D Drevon, C , chloride. Chinese r Ducatman, Vinyl chi errations - Edmonds. I uai malfe Edmonds, I James (IS formatior commumt Fleig. I-. an chloride J Funes-Craw berg, A.I Cnromoso: chloride L Green. T., a^ chloride v act, 22,2 Hansteen, Helda&s genetic f Infante, P weiler, a ride Lar Infante, P I the Lire re- oss .'OtS 0\v - JU'- 'es, :es for joi- of poin uch :he ope ;>ebearnd niHIiid :ry ^ss Talu'th ire he ed ed re-e:ts rW as Id rs of ig al to on in rh bie ;n m rss BIRTH DEFECTS \ND v:\VL CHLORIDE 369 of birth defects in the highly exposed dis tricts twice as high as in the poorly exposed one* was 80G_ This probability would have been 99G had the excess been three times as hich ACKNOWLEDGMENTS This research wa* conducted in fulfillment of contract No 69-02 2780 by the Department of Social and Proventi\e Medicine. La\a3 University, under the sponsorship of the U.S, Environmental Protection Agency It* con tent lias been made the obiect of a complete report published bv the U S Government Printing Office: 19Sl-757-012'7327 The autnors are most grateful to M. James Kempf, Drs David Mage. 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Caputo (2971) Oncogeruc response of rat skin, lungs, and bones to vinyl chloride. Cancer Res., 32.516-522. Cttft 006204 t C THERIAULT, H ITURRA AND S GINGRAS Walter, S C , and J M Elwood (1975) A test for seasonal ly of events wrth a vanaoie population at risk. Br J Pvevent Soc Mt*d , 29 18-5H W'axweuer. R J , W Stnnger, J K Wagoner, J Jones, H Falk and C Carter U9761 Neoplastic risk among workers exposed to vnny) chloride Ann, N Y Acad Sci 271 40-4S Norma! c Fetus St Examina i abs: amir. fetus obtai hyari The intro carnivore, n togenesis as commonly t morphs, is i the several a '77) m usmf under labor can be accu Ferrets, seasonal br the breedir. Mai^^o A sid^^lbre mal^W art processes ir in the fem Methods of < are describe Our met! adult male condition ir of artificial they are rec they are trar (14 hours of weeks they by the condi A few male that a situa are availab is not a cor the reader Gulamhus* teratogenic Estrus is mg of the ' ter mating the beginr.