Document npL8v9pg79QXYOkYZgGJ4Vx4w

l R&S 108074 ------ BIO-MEDICAL RESEARCH DOCUMENT DESCRIPTION FORM 63 0000168 68 69 76 Duplicate in all cards:--> /9 ?Q______ j year as-1961- File number [Right justify [Numeric only] Author(s), as Last Name FS (No Punctuation) and coden for journal as JAMA preceeded by one blank space l -fain P. F- F 1.! n . I /<. 3 Mc^M ichfl-e-l Arf f (- UJclkiup-i !s,i~ Fa^/fc F <rT ^ 7778 Sub-Index Code 61 62 11 12 13 Title of Report; end with space-hyphen-hyphen-space. ]fo--l-l-o---w- w--it--n- ---i-n--d--e--x- _ie.r. ms, separated from each other with comma-space. Avoid other punctuation; do not abbreviate. 12 ,, 61 62 I ....... . io _fRi'S.A-'b U/n y j Cll lan~ i <J ^ - F? c'V-,'F'>J . 21 22 'rV )-'- >,r d--. /3i -.(i'r-.uif ' FFsiZ'C' ^ y 7 /.it-' F- j^ ,, L> / ^y L` ''-yFi 7^'t, c "j // / 23 24 Source (Journal, Vol., Number, Pages, Date ) 12 R > i fXytOF-H---- <ryy.;-FcJ--------J^/1. u Iff-' L-: , ,i >' r .11. 3 /7;^F ----- 61 62 31 32 r {/ Brief Summary 12 10 SUMMARY: 61 62 61 62 63 64 000016$ 734 THE LANCET, AERIE 3, 1976 Occasional Survey GENETIC RISKS OF VINYL CHLORIDE Petek F. Infante Joseph K. Wagoner Anthony J. McMiciiah. Rickako J. Waxweieek Henry Falk. Division ofSurveillance, Hazard Evaluations and Field Studies, National Institute for Occupational Safety and Health, and Bureau of Epidemiology, Center for Disease Control; and School of Pul-lie Health, University of North __ Carolina Summary A study of pregnancy outcome among wives of workers exposed to vinyl-chlor ide monomer (v.c.At.) indicated that, in comparison with controls, there was a significant excess fetal loss in the group whose husbands had a primary exposure to v.c.M., whereas no differences between the groups were observed before the husbands' exposures. The difference in feta! death-rates for the post-exposure comparisons was a reflection of a greater fetal loss associated with the wives younger-aged husbands. The significant excess did not seem to be the result of bias from interviewers, re spondents, nor from women who had experienced chronic abortions weighting the results. These findings, in conjunction with the demonstration of a mutagenic response via microbial test systems and with observa tions of significant excesses of chromosomal aberrations among workers exposed to v.c.ai., raise scientific and public-health concern for the possible genetic risks of v.c.M. to man. In the past year, several reports have indicated that vinyl-chloride monomer (v.c.M.) is mutagenic in micro bial test systems.1'3 v.c.M. metabolites also have in duced mutations in mammalian cells.3 Likewise, reports from four countries have shown an excess of chromoso mal aberrations in lymphocytes of workers exposed to v.c.M. compared with cotuiols.5'* However, Purchase ct al.7 have stated (though no animal data were presented), that the mutagenic effects of v.c.M. expressed as chro mosomal aberrations in lymphocytes in humans do not occur in germ cells in mice; they concluded that the potential danger of mutagenic effects on the fetus via sperm seemed unlikely to exist. In a study without con'trols, SchkolT observed fetal death-rates among wives of V.C.xt. workers that ranged from 7 to 14 per 100 preg nancies.^ These rates appear to have been higher than expected.10 To develop further data on this question, pregnancy outcome has been studied among the wives of workers exposed to v.c.M. All current v.c.M. polymerisation and polyvinyl- hlorule (t'.v.c.) fabrication workers were in cluded lor study together with a similar number of cur rent rubber workers (SL of all such workers) selected from work areas relatively free from known toxic materials and matched as a group to the v.c.M. workers by age. Group participation rates ranged from 62 to 77%. Data for the wives of v.c.M, polymerisation workers (primary v.c.M. group) were Contrasted with data for the wives of t'.v.c. fabrication and rubber workers ("controls''), vvho were known to have had very low or no V.c.M. exposvne, respectively. A total of y5 v.c.At. polymerisation and 158 rubber and t'.v.c. fabri cation workers were interviewed. Paternal age, preg nancy outcome, and estimates for the time of conception of all pregnancies were ascertained by interview in Oct ober, 1974, from males employed at a rubber manufac turing, r.v.c. fabricating, and v.c.M. polymerising facil ity. As part of a larger survey of worker health, date of first employment in the job categories was determined from company records. Mean paternal age, total number of conceptions, total number of fetal deaths (defined as any product of conception not born alive), and fetal deaths per 100 conceptions were then computed for each group prior to and subsequent to the worker's date of employment. No interviews were conducted with workers' wives and no data were obtained concerning maternal age, except indirectly througlt paternal age. Since fetal loss is known to increase with ascending parental age, the fetal death-rates for the primary v.c.At. exposure group were age-adjusted to the control group. Table i shows the age-adjusted fetal death-rates for wives of the primary v.c.At. exposure group versus the control group, both prior to and subsequent to each group's respective exposures. Among pregnan cies occurring prior to exposure, fetal death-rates were 6-9% for the controls versus 6-1% (age-adjusted) for the primary v.c.At, exposure group. These rates were not significantly different by Mantel-Hacnszc! Chi-square testing.13 Among pregnancies occurring subsequent to the husband's exposure, the difference in frequency of fetal deaths between groups was significant at t*<0-05 (y_3=4-00, df=l).u Although the underlying dis tributions differed, mean paternal ages were virtually the same---30-4 versus 30-2 years. The significant dif ference between the groups subsequent to exposure was a reflection of a relatively greater fetal mortality-rate as sociated with younger-aged husbands in the primary v.c.At. exposure group. Among pregnancies occurring subsequent to exposure, the fetal mortality-rates associ ated with husbands 30 years of age and older for the pri mary v.c.At, exposure and control groups were 9/69 (13-0%) and 17/142 (12-0/c,), respectively; whereas, for TABLE I---MEAN PATERNAL AG I , NL'MUFR OF PRFUNANCIFS, AND FETAL V.c.DEATII-RATF.S ACCORDING TO HUSBAND'S EXPOSURE -- prior to hmbdnJ's exposure: Number of fjnwhes Mean paternal aye at conception (\r.) Number of fetal deaths amony "itn Number of pregnancies Aye dJiuvtcJ (ct.it deaths/100 prey t (O ItuihjnJ'i tipiiinrc' Number of families Mean paternal aye at t.onupimn |vr ) Nmnbi r ol fetal Heath* jmony hivcs Momler of preynatwm AyeaJmxivvt let al dcjthv'lOil pny J Primary "Controls"* v.c.M. exposuref 93 23 0 11 139 6-9 in 30*4 24 in M 70 161 15 148 61 62 30-2 23 139 us; *Kul'!vf aJ t-A \. fjl'rixjiinii workers, fvt jvjl\ nu nwtnm wiirLirs. }KjU\ jjjf jJtU'i'-J to ''unttrul" ynmp iMU-nul cc distnhutmn ^.Sub*vvpKH u* Uvt'luMxl'x e^-osure* the v <| anumy HJi ii^infu Jill l> chalvr in the )'t iiit.iM i t At op. >'tire ptottp (Itjn in I lie "uni. U'vO OM or m thv smjt yroup prior to hu'ihjnd's n|nnufi' vl *,U U*j by gc vJjtiiltJ tin square uotuy n R&S 108075 9^080t 0 l 33 #> CO f THE I.ANCtr, APRIL 3, 1976 735 TARtk H -- Sit AS PAT1 R\U Al.ti M'! K OF t' G'-AWlf S, AM) H ML Dl ATH'KAl J S AITOXDING IO m*s M\M)'S V,C. HI'OM'KI * \U UHN(i PXItiNlMIt S OK WOM) ^ VM1H * 3 KHl. 01 AU1S I'nmjry '`I'amrof*"' \ r.M. cipnsurcf Prior /o AuifMii.fj t'x/vii/rr' Mcill p.vUTnjl j^C 1 conception Number of ft i j! deaths amnnp umjj NuiuIkt of pregnancies Agc-aJiustcJ fet.d JfcMihv/lUO pro*,-,* Subnotion to hmhunJ'i exporter. Mcjn paicm.tl age----------------at conception ;vr.) Number of fowl d<a(h\ among smncs Number <vf pregnancies Age-atimsieJ feta) deaths/K)0 preg4 230 11 159 6-9 30-2 ]> 265 6-8 26-3 9 141 3) 30 8 14 no ,8 Rubber and h.\ < , fabrication vtorkers. fv.c. poIyin<mauot\ uurLcrv JRaiei age-adjusted to `'control" paternal aye distribution. husbands less than 30 years of age, fetal mortality was 14/70 (20-0'f) for the primary v.c.M. exposure group compared with 7/131 (5-377) for the control group (these data are not shown in tables.) Furthermore, intragroup comparisons indicated an increase in age-adjusted rates " : primary v.c.M. exposure group from 6-1/7 posure to 15-8/7 subsequent to the husband': ..pu ..re, This difference also was significant, p<0-02 (-/3=5-51, df=l),u Similar comparison for rates in the control group, 6-957 versus 8-8%, indicated no significant difference. To determine whether women who had chronically experienced abortions might have weighted the results in favour of a high r fetal death-rate in the primary v.c.M. group subsequent to husband's exposure, pregnancies of women who had more than two abortions were elim inated from the analyses and the data were recalcu lated to determine whether or not the trend was main tained. The decision to exclude all pregnancies among families associated with more than two abortions was made without prior knowledge of how these families were distributed among the exposure categories. The data in table li show that the trend was maintained. Prior to exposure, the fetal death-rates in the enrol and primary v.c.M. exposure groups were 6-957 ,md 3-1% (age-adjusted), respectively, whereas, after expo sure, the rates were 6-857 and 10-857, respectively. Sub sequently, data were eliminated for pregnancies of women who had experienced, firstly, more than one abortion, and, secondly, more than three abortions, and each time the trend was maintained. No changes in rates for controls were observed, whereas a 2-3-fold increase was observed in the primary v.c.M. group subsequent to exposure. To determine whether differences in fetal loss might have been the result of one or two interviewers weight ing the resulis, the data were analysed by imlividti.il in terviewer. The results demonsiraied a general trend for each interviewer to report a higher ascertainment among v.c.m. polymerisation workers than among the control group. Further, the possibility was entertained that the inter val between the d -ie ol interview and llie date of feta! loss might have influenced the results through dif ferences in recall. The interval, however, was estimated to have been about two years less for controls, suggest ing that, if a bias did exist, it would have been towards a greater ascertainment in the control group. In some cases, the worker failed to indicate the ages of his children and in other cases he was unable to recall the approximate time of his wife's abortion; therefore, the data were analysed to determine the distribution of fetal death-rates among the respondents in each occupational group who did not complete the interview properly. The difference in fetal death-rates between groups was very slight. Finally, the workers may have been subject to bias resulting from prior knowledge of known hazards of vinyl chloride. However, the workers themselves did not always know into which of our employment categories they were being allocated, For example, several v.v.c. fabrication workers who were included in the control group thought that they had a primary v.c.m. exposure as a fabrication worker. In addition, the questions regarding pregnancy outcome were contained in a much larger interview-questionnaire, the results of which demonstrated very few significant differences with no consistent bias for the parameters ascertained between the workers with a primary v.c.m. exposure, and the other groups. This observation as well as several others presented above tend to support the validity of the study. In summary, a significant excess of fetal loss was observed among wives of workers following exposure to v.c.m. The excess did not appear to be the result of bias from interviewers or respondents, nor from women who experienced chronic abortions weighting the results. Several mechanisms by which such fetal loss may arise are suggested. Either feta! or maternal toxicity or germcell mutagenesis in the mother through indirect v.c.m, exposure from the father might be considered, although these mechanisms seem highly unlikely in view of the highly volatile nature of v.c.m.15 When the findings of the present study arc taken in conjunction with the prior demonstration of a mutagenic response via microbial test systems and observations of significant excesses of chromosomal aberrations among workers exposed to v.c.m., the leading possibility is germ-cell damage in the father through direct v.c.m, exposure. The increased fetal mortality among wives of workers subsequent to v.c.m. exposure now raises serious scientific and publichealth concern for the possible genetic risks of vinyl chloride to man. Requests for reprims should be addressed 10 P I-'.!., N.1.0.S.1I., Post OlPcc Pudding, Ruom 515, Ciueitimilt, Ohiu 45202, U.S.A. REFERENCES 1. IIjMscIi, II., Mjlunelk, C , Momc-artO. K Ini J Canter. 1975. IS, 42V 2. l-tprieno, S' , lljrale, K,, VaroiKtlli, S . el al. Mutation Aei (m the pto,)- 3. Rartnug, l1., Jnhan,,on, A., Itamel, I i.hnictvtcr, C. A. AmSia. 1975, 3, 194. I Iluherman, L.t lljrlHh, II , Saths, I., hit J Canter, 1975, 16, 619 5. Duealman, A , lit,,, Shorn, K , Selil.,.11, 1 1 Stuimnnt Ktt 1975, 31, 161. 6. luuev l.r.iMi'lo. |-,, L.utiheri. 11. l.mJ't. . J. l-.hruiNri;. I.., Naljraian, A. I.. Oneriiun( I.OV .If, S. Lam rl. 19' 5, i, 4 59, 7. Purchase. 1 I'. II . ln,li.ilJ,,'M, l.. It . An.l. r,.m, 1) 161J 1975.11, 410. S. ltilU',i.iJ, I , I ltd, 1 wiisen. I , 11i,pii!!i,lie.l 9. .VliU'fl. |. J , N I I IIS l .mlr,,,i,r iin I'ohlie llejlili Imi'lieJiioto, of Com ponent, ,*f rl.i.i.,, M.iiiulj.itire, l'i,',lmr>i. North t.-trohna, Jtl>, 1471, 10. Infante, P 1 11. Slupiro, S , 12. Mantel, N 13. I'ttueJ St. tclert , Ann SY A,aJ .5,1 (in the i1,,',,! 55 ,l)en,e,P M Mill-anh p 141,2.40,7. i ii-rd, 55' J Sain Can,ti Inn >454.22,7)4. uMitmnteitt.i! l"iou,lioti Agriiev, witt|'liitg Jttj anjl,st, of i.tmc, u,5 Ml siii>t tltlortje. Contra,l tit, 66 U1 2646. Jan, r.4,, January ^b, i y / d /7 / R&S 108077 GENETIC RISKS OF VINYL CHLORIDE By Peter F. Infante i dosoph K. l/o goner Anthem/ J. McHichael Richard J. War.wei 1 or Henry f a 11: 0 Division of Surveillance, Hazard Evaluation:; and Field Studies National 1 nst. i tut r. for Occupational Safety and Health, Ctireau of Epidemiology., Center for Disease Control, and + School of Public Health, University of il. Carolina Mail iiuj Address: NIGS!!, Posl; Office Building, Room 515 Cincinnati. Ohio <15202 USA c R&S 108078 t In the past: year, several reports have indicated that vinyl chloride jo monoiner (VCM) is Mutagenic in microbial test systems. ~ VCM metabolites also have induced mutations in mammalian cells.^ Likewise, reports from four countries have shown an excess of chromosomal, aberrations in lympho cytes of workers exposed to VCM as compared to controls.HoweverPur chase et al./ have stated recently., though no animal data were presented, that the mutagenic effects of VCM expressed as chromosomal aberrations in lymphocytes in humans do not occur in germ cells in mice; they concluded that the potential for mutagenic effects on the fetus via sperm seemed unlikely. In a study without, controls, Selikoff observed fetal death rates q among wives of VCM workers that ranged from 7-14 per 100 pregnancies. These rates appear to have been higher than expected.^ lo develop further date on this question, a study of pregnancy out come was made among the wives of workers exposed to VCM, All current VCM polymerization and polyvinyl chloride (PVC) fabrication workers were in cluded for study together with a similar number of current rubber workers (CM of all such workers) selected from work areas relatively free from known toxic materials and matched as a group to the VCM workc-rs by age. Group participation rates ranged from 62-77 percent. Data for the wives of VCM polymerization workers (primary VCM exposure group) were contrasted with data for the wives of PVC fabrication and rubber workers ("controls"), who wore known to have had very low or no VCM exposure, respectively. A total of 95 VCii polymerization and 158 rubber and PVC fabrication workers were interviewed. Paternal age, pregnancy outcome and estimates for the time 2- - t of conception of all pregnancies were ascertained by interview in October, 1974, from males employed at a rubber manufacturing, PVC fabricating and VCM polymerizing facility. As part of a larger survey of worker health, date of first, employment in the job categories was determined from company records. Mean paternal age, total number of conceptions, total number of R&S 108079 fetal deaths, defined as any product of conception not born alive, and fetal deaths per 100 conceptions were then computed for each group prior to and subsequent to the worker's date of employment. No interviews were conducted with workers' wives and no data were obtained concerning maternal age, except indirectly through paternal age. Since fetal loss is known to increase with ascending parental age, the fetal death rates for the primary VCM exposure group were age-adjusted to the control group. Table I shows the crude and age-adjusted fetal death rates for the wives of the primary VCM exposure group versus the control group, both prior to and subsequent to each group's respective exposures. Among pregnancies occurring prior to exposure, fetal death rates were 6.9% for the controls versus 6.1" (age-adjusted) for the primary VCM exposure group. These rates were not significantly different by Mantel-Haenszel Chi-square testing. Among pregnancies occurring subsequent to the hus band's exposure, the difference in frequency of fetal deaths between groups ') I o was significant at P-:0.06(x '=4.00,df=l). Although the underlying distri butions differed, mean paternal ages wore virtually the same, 30.4 versus 30.2 years. The significant difference between the groups subsequent to exposure was a reflection of a relatively greater fetal mortality rate associa ted with younger-aged husbands in the primary VCM exposure group. Among preg nancies occurring subsequent to exposure, the fetal mortality rates associated with husbands 30 years of age and older for the primary VCM exposure and control groups were 9/69 (13.Of) and 17/142 (12.07), respectively; whereas, -3- for husbands less than 30 years of age, fetal mortality was 14/70 (20.0%) for the primary VCM exposure group as compared to 7/131 (5.3%) for the con- trol group. (These data arc not shown in Tables). Furthermore, intragroup comparisons indicated an increase in age- adjusted rates for the primary VCM exposure group from 6.1% before exposure to 15.8% subsequent to the husband's exposure. This difference also was - ' "" p lO significant, P<0.02(x'=5.5l ,cif=l). Similar comparison-for_rates in the control group, 6.9% versus 8.8%, indicated no significant difference. -' To determine if woman who had chronically experienced abortions may have weighted the results in favor of a higher fetal death rate in the pri mary VCM group subsequent to husband's exposure, pregnancies of women who had more than two abortions were eliminated from the analyses and the data were recalculated to determine whether or not the trend was maintained. The decision to exclude all pregnancies among families associated with more than two abortions was made without prior knowledge of how these families were distributed among the exposure categories. The data in Table II show that the trend was maintained. Prior to exposure, the 'fetal death rates in the control and primary VCM exposure groups were 6.9% and 3.1% (age-adjusted), respectively, whereas, after exposure, the rates were G.8% and 10.8%, re spectively. Subsequently, data were eliminated for pregnancies of women who had experienced, firstly, more than one abortion, and, secondly, more than three abortions, and each time the trend was maintained, Mo changes in rates for controls were observed, whereas, a 2-3 fold increase was observed in the primary VCM group subsequent to exposure. To determine whether differences in fetal loss may have been the result of one or two interviewers weighting the results, the data were analyzed by individual interviewer. The results demonstrated a general trend for each R&S 108080 B&S 108081 4 . * * V interviewer to report a higher ascertainment among VCM polymerization workers as compared to the control group. Further, the possibility was entertained that the time interval between the date of interview and the date of fetal loss might have influenced the lesults through differences in recall. The time interval, however, was es timated to have been about two years less for controls, suggesting that if a bias did exist, it would have been toward a greater ascertainment in the control group. In some cases, the worker failed to indicate the ages of his children and in other cases he was unable to recall the approximate time of his wife's abortion; therefore, the data were analyzed to determine the dis tribution of fetal death rates among the respondents in each occupational group, who did not complete the interview properly. The difference in fetal death rater, between groups was minimal. Finally, the workers may have been subject to bias resulting from prior knowledge of known hazards of vinyl chloride. However, the workers them selves did not always know into which of our employment categories they were being allocated. For example, several PVC fabrication workers who were in cluded in the control group thought that th'e^iiad a primary VCM exposure as a fabrication worker. In addition, the questions regarding pregnancy out come were contained in a much larger interview-questionnaire, the results of which demon:;traced very few significant differences with no consistent bias for the parameters ascertained bet;,'eon the workers with a primary VCM exposure as compared to the other gtoups. This observation as well as several others presented above tend to support the validity of the study. In summary, a significant excess of fetal loss was observed among wives of workers loll owing exposure to VCM. The excess did not appear to be the result of bias from interviewers, respondents, nor from women who experienced -5- chronic abortions weighting the results. Several mechanisms by which such fetal loss may arise are suggested. Either fetal or maternal toxicity or germ coll mutagenesis in the mother through indirect VCM exposure from the father might be considered, although these mechanisms seem highly unlikely in view of the highly volatile characteristic of VCM. 13 When the findings of the present..s.tudy ..ere taken in conjunction with the prior demonstration of a mutagenic response via microbial test systems "and observations of sig- nificant excesses of chromosomal aberrations among workers exposed to VCM, the leading possibility is germ cell damage in the father through direct VCM exposure. The increased occurrence of fetal mortality among wives of workers subsequent to VCM exposure now raises serious scientific and public health concern for the possible genetic risks of vinyl chloride to humans. R&S 108082 b REFERENCES 1 R&S 108083 1. Bartsch, H., Malaviclle, C. anci Montesano, R. Human, rat and mouse 1ivcr-mediated mutauenicity of vinyl chloride in S. Typhimurium strains, Int. J. Cantor, 1975, 15, 429. 2. Loprieno, II., Ramie, R. , Varoncelli, S., ct al. Evaluation of the genetic effects by vinyl chloride monomer (VCM) under the influence of liver microsomes, Mutation Res, In press. 3. Rannug, LI., Johansson, A., Ramel, C. and 1,'acht.meister, C. A. The mutagenicity of vinyl chloride after metabolic activation, Ambio 1974, 3, 194. 4. Huberman, L\, Bartsch, H. and Sachs, L. Mutation induction in Chinese hamster V79 cells by two vinyl chlorine motabo.l i tes. chioroethylone oxide and 2-chloroacctaldehydc. Int._J. Cancer, 1975, 1C, 639. 5. OucaLilian, A., Hirschhen:, K. and Selikcff, I. J. Vinyl chloride exposure and human chromosome aberrations, Mutation Res, 1975, 31, 163. 6. Funes-Craviotu, F., Lambert, R., Lindstcn, J. et al. Chromosome aberrations in workers exposed to vinyl chloride. Lancet 1975, i, 459. Purchase, I.F.H., Richardson, C.R. and Anderson, D. Chromosomal and dominant lethal effects of vinyl chloride, Lancet 1975, ii, 410. Hillestad, L. and Thiis-Evensen, E. Preliminary report on the medical examination of 233 employees at the PVC plant, Norsk Hydro a. s., Porsgrunn Fabrikker. Unpublished manuscript. N1EHS Conference on Public Health Implications of Components of Plastics Manufacture, Pinehurst, North Carolina, July, 1974. Selikoff,J.J. Statement during discussion. Infante, P.F. Oncogenic and mutagenic risks in communities with poly vinyl chloride production facilities, Ann. N.Y. Acad. Sci, In press. Shapiro, S., Jones, C.W. arid Denser, P.M. A life table of pregnancy terminations and correlates of fetal loss, Mill bank Quarterly, 19(52, 40, 7. Mantel, N. and Haonxcl, W. Statistical aspects of the analysis of data from retrospective studies of disease, J. Natl. Cancer Inst, 22: 719-743, 1959. Urn ted States Environmental Protection Agency, Sampling and analysis of select toxic substances, Task III, Vinyl Chloride. Contract No. 68-01-2646, January 20, 1976. table i Mi:AN PATERNAL AGE, K :L;ER OF PREGNANCIES AND FETAL DEATH RATES ACCPO'MNu TO HUSBAND'S VC EXPOSURE "CONITIOLS"* PRIMARY VCM EXPOSURE11 \1 > lu' '>!.!\ TO I-USDAND'S EXPOSURE NUMBER OE FAMILIES . MEAN PATERNAL ACE AT CONCEPTION (YEATS) NUMBER OF FETAL DEATHS AMONG WIVES NUMBER OF PREGNANCIES ACC-APJUSTED FETAL DEATHS/100 PREG.0 95 23.0 n I 59 6.9 70 26.4 ' ' 15 148 6.1 sussrnj'JIT TO HUSBAND' S EXPOSURE R&S 108085 IBCR OF FAMILIES MEAN PATERNAL ACF AT CONCEPTION (YEARS) NUMBER Of FETAL DEATHS AMONG WIVES NUMBER OF PREGNANCIES AGE-ADUUSTFH FETAL DEATHS/!DO NTEGU' 113 30.4 24 273 8.8 62 30.2 23 139 15.8* + RUBBER AND PVC rARklGATTOM W,,;;;,EPS. * VC POLYMERIZATION WORKERS. 0 RATES AGE-ADJUSTED TO "CONTROL" GROUP PATERNAL AGE DISTRIBUTION. * SUBSEQUENT TO HUSBAND'S EXPOSUK ; THE FREQUENCY OF FETAL DEATHS AMONG WIVES WAS SI ON II ICANTLY GREATER IN T!i! i f: IMARY VCM EXPOSURE CROUP AS COMPARED TO THE "CON^jOi.S" (P-O. OF) OR TO THE Fk;'RliEMCV IN THE STUDY CROUP PRIOR TO HUSBAND'S EXPOSURE (P<0.02) BY ACE-ADJUSTED Cl!! - SQUARE TESTING.12 TABLE II MEAN PATERNAL AGE, NUMBER OF PREGNANCIES AND FETAL DEATH RATES ACCORDING TO HUSBAND'S VC EXPOSURE EXCLUDING PREGNANCIES OF WOMEN WITH > 3 FETAL DEATHS "CgNTRpLS"H' PRIMARY VCM EXPOSURE*' " PRIOR TO HUSBAND'S EXPOSURE MEAN PATERNAL AGE AT CONCEPTION (YEARS) NUMBER OF FETAL DEATHS AMONG WIVES NUMBER OF PREGNANCIES AGE-ADJUSTED FETAL DEATHS/100 PREG.0 23.0 n 15S 6.9 26.3 9 141 3.1 SUBSEQUENT TO HUSBAND' S EXPOSURE MEAN PATERNAL AGE AT CONCEPTION (YEARS) NUMBER OF FETAL DEATHS AMONG WIVES NUMBER OF PREGNANCIES AGE-ADJUSTED FETAL DEATHS/'! 00 PREG.0 30.2 18 265 6.8 30.8 14 120 10.8 RUBBER AND PVC FABRICATION WORKERS. * VC POLYMERIZATION WORKERS. 0 RATES AGE-ADJUSTED TO "CONTROL" PATERNAL AGE DISTRIBUTION. 30 fio (/) o c0r>9