Document B5g5NVjnZKd16J5ekMv8xGYxX

* fl" ; CO. m nr ' "in Occasional Survey GENETIC RISKS OF VINYL CHLORIDE Peter F. Infante K.Joseph Wagoner Anthony J. McMichael Richard J. VC'axweile* Henry Falx Division ofSurveillance. Hazard Evaluations and Field Studies, National Institute far Occupational Safety and Health, and Bureau of Epidemiology, Center for Distate Control; and School of Public Health, University of North Carolina Summary A study of pregnancy outcome among wives of workers exposed to vinyl-chior* ide monomer (v.c.M.) indicated that, in comparison with controls, there was a significant excess fetal loss m the group whose husbands had a primary exposure to V.CJA., whereas no differences between the groups were observed before the husbands' exposures. The difference in fetal 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, spondents, nor from women who had exponent chronic abortions weighting the results, in conjunction with the demonstraflGmj)oi\a rjlfutagemc response via microbial test systems'Smfcjvuh observa tions of significant excesses of chromosomal aberrations among workers exposed to v.c.m., raise scientific and public-health concern for the possible genetic risks of v.cja. 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-* v.c.m. metabolites also have in duced mutations m mammalian cells.4 Likewise, reports from four countries have shown an excess of chromoso mal aberrations in lymphocytes of workers exposed to v.c-M. compared with controls.5-11 However. Purchase et al.' 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 2 study without con trols, Selikoff observed fetal death-rates among wives of v.C-M. 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 ihe wives of workers exposed to v.c.m. All current v.c.m. polymerisation and polyvinyl-chloride p.v.c. ' tafcncation workers were in cluded for study together with a similar number of cur rent rubber workers , 8'r 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-partteipauon rates ranged from-62 to 77T. Data for the wites of v.c.m. polymerisation workers -primary v.c.m. group' were contrasted with data for the wives of r.v.c. fabrication ar.d rubber workers ."controls",, who were known 10 ha\c had verv low or no v.c.m. exposure, respectively. A total of 95 v.c.m. polymerisation aftd 158 rubber and p.v.c. fabri cation workers were interviewed. Paternal age, preg nancy outcome, and estimates for the tune of conception of all pregnancies were ascertained by interview in Oct ober, 1974, from males employed at a rubber manufac turing, p.v.c. fabricating, and v.c.m. polymerising facil ity. As pan of a larger survey of worker health, date of first employment in ihe 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. N'o 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 v.c-m. exposure group w'ere age-adiusied to the control group. Table 1 shows the age-adjusted fetal death-rates for wives of tho-sprimary v.c.m. exposure group versus the corffrol g&fp, both pnor to and subsequent to eadrdtrjfcipVreipive exposures. Among pregnan- jgf oceumM -prior to exposure, fetal death-rates were lyorTnecontrois versus 6- IT .age-adjusted; for the !mary v.c.m. exposure group. These rates were not significantly different by Mamel-Haenszel 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 p<0-Q5 v/J=`T0b, df=l).13 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 grouns subsequent to exposure was a reflection of a relatively greater fetal mortaiitv-rate as sociated with younger-aged husbands in the primary v.c.m. 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.m. exposure and control groups were 9/69 (13-0T) and 17/142 (12-OT), respectively; whereas, for TABLE 1--MEAN PATERNAL ACE, NVMBEJt OF PREGNANCIES, AND FETAL DEATH-RATE* ACCORDING TO HUSBAND S \.C. EXPOSURE -- to husband's rxpoturt; Number of families Mean paternal aft ai conception ' Slumber et leu! Jcjttu among wivo Number of pregnancies Aft-aJmsicd fetal kaihv )00prct4 S'mI'ji10 aaaroWj exposure; Namber ol tatntbd Mean paternal act at vofK.emon vr. Number M tdal Vain* among na Number nl premafwte* Atf-aJiu'icj letal icaint l'KJ pfeg-- Primary "Comm!**11* vxj4. taposoret 95 23 0 11 159 6-9 113 30-4 24 171 i-i 70 26*4 IS 141 *'l 62 30*2 :j 139 i; Kobbcr aftj r l.t ubruamw uurk**v "v 1, |Stkincn\4iiA*n i&atcwwf u hbMnl" dvuf patenui id Jitiftbvmm. \btnva;eft( tit rtptwrc. tfic ut'QurfttT or itui jtjth* <m **1 Mfiutisjftm (fTcjicr m me rrimarv t t. eipoture ^uup -,iun m tbe ' won- irtw*'' or m the tiuJ* wrmip prior to aubahJ esponurc r-.UU..b\ chi-s^uarr letting " BFS 005223 TNI LANCIT, APRIL 3, 1976 735 TAIL! II---- NtAH FaTIANAL ACl, OF F*t6NCIt J, AND FtTAl DtATH*IATES ACtOtbfvG TO HUHANO'} V.c. ElPOUJtE flCLL'O/HG PUG*ANCIE or WOMEN with * 3 fetal deaths 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 -- Pnmary a greater ascertainment in the control group. In some "Control"* v.cj*. dpoturtt cases, the worker failed to indicate the ages of his f^ncr te ktukamd'i r*posv+t: children and In other cases he was unable to recall the Mean paternal t|t at conception vr./ Number of fetal deaths among wives Number of prcgnancici Age-aJiusted fecal kathv'l00pref4 5vt>iyu/af lu exposure: Mean paternal age at conception yr.) Number of fetal deaths among wive Number of prcfnanua Agt-aJunoJ fetal deaths/100 prcg4 53-0 li 139 -9 302 11 2*5 61 '54 1 9 141 3-1 30* 14 120 10-1 approximate time of his wife's abortion; therefore, the data were analysed to determine the distribution of fetal death-rates among the respondents tn 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 P.v.c. fabrication workers who were included in the control *Rubtoer And r v.c. fabrication workers. f%\C. polyratfuJnon orken. tJUm age-adiusi&l 10 "contror* paternal age distribution. 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 husbands less than 30 years of age, fetal mortality was larger interview-questionnaire, the results of which 14/70 (20-07) for the primary v.c.M. exposure group demonstrated very few significant differences with no compared with 7/131 (5-37) for the control group consistent bias for the parameters ascertained between (these data are not shown in tables.) the workers with a primary v.c.M. exposure, and the Furthermore, intragroup comparisons indicated an other groups. This observation as well as several others increase in age-adiusied rates for the primary v.c.M. exposure group from 6-17 before exposure to 15-87 presented abovetend to support the validity of the study. 1 subsequent to the husband's exposure. This difference ItW, Tftmm^yTaJsigntficant excess of fetal loss was also was significant, p<002 (y3=5-51, df=l).1J Similsq^ j Jw^ong wives of workers following exposure to comparison for rates in the control group, fi^'.^CyhrtuQsj'\| v.c..wl>The excess did not appear to be the result of bias 8-87, indicated no significant differences *0--, O' from interviewers or respondents, nor from women who To determine whether worsCnJhvftp had^prorocaliy experienced chronic abortions weighting the results. experienced abortions might havEN^jghtra the results in Several mechanisms by which such fetal loss may arise favour of a higher fetal death-raft in the primary \.c.m. are suggested. Either fetal or maternal toxicity or germ- group subsequent to husband's exposure, pregnancies of cell mutagenesis in the mother through indirect v.c.M. women who had more than two abortions were elim exposure from the father might be considered, although inated from the analyses and the data were recalcu these mechanisms seem highly uniikdv m view of the lated to determine whether or not the trend was main highly volatile nature of v.c.M.11 When the findings of tained. The decision io exclude all pregnancies among the present study are taken in conjunction with the prior families associated with more than two abortions was demonstration of a mutagenic response via microbial made without prior knowledge of how these families test systems and observations of significant excesses of were distributed among the exposure categories. The chromosomal aberrations among workers exposed to data in table II show that the trend was maintained. v.c.M., the leading possibility is germ-cell damage in the Prior to exposure, the fetal death-rates in the control father through direct v.c.M. exposure. The increased and primary v.c.M. exposure groups were 6-97 and fetal mortality among wives of workers subsequent to 3-17 (age-adjusted;, respectively, whereas, after expo v.c.M. exposure now raises serious scientific and public- sure, the rates were 6-87 and 10-87, respectively. Sub health concern for the possible genetic risks of vinyl sequently, data were eliminated for pregnancies of chloride to man. women who had expenenced, firstly, more 'than one abortion, and, secondly, more than three abortions, and Refluent for rtpnnis thould be *ddreited io P.F.t.. N.I.O.5.H., Post Office Budding, Room 51 J, Cincinnati, Ohio 45502. L.S.A. each time the trend was maintained. No changes in rates amRfNets for controls were observed, whereas a 2-3-fold increase was observed in the primary v.c.M. group suDsequent io exposure. To determine whether differences in fetal loss might I. Hinwh. H-. MjJjvielle. C.. Momeww. R- li. J Ctntrr IV'5, 15, 45V 5 l.-pncnu. N . lljraic. R.. Vurniwciu. S.. cl 4l. .Ilfciuiion Aei in the preu . }. Rinnug. L.. 5oh*&Mon. A.. Keltic!. C. W Achmruier, C. A. Am&ju 1?4, S, IH, A. Hube-min. I1..* (UrfKh. H., Such*. L. lt J Cencc, IV'!, 14. 6.1V. have been the result of one or two interviewers weight ing the results, the data were analysed by individual in ! Ihuiettnen, A., llinchhom, h. Sc.iholf. 1 ] lli.iufi.iR Act. iv'!. 31. 163. 6 l-unevv.rj,iiHu. K. Li-nrvn, B-. Unuttcn. J,, Lhrcntvtc, L- NitirAiAR, A r . tHicnnin-uoltur. s Luncci, 1V*5, i. e!S terviewer. The results demonstrated a general trend for each interviewer io report a higher ascertainment among v.c.M. polymerisation workers than among the rcrrheic. 1, F M . KicherJkin. 1_ R . AnUenoft. 13, u-ij 1V-5, Li. 11U H. Hi!l.-,ied. L-, 1 hi:,-1 ,enxn. i I npubli\Ac4. V hehtull. I J . \ l.h U.S L*n:nrn.c nn l1 uCli. Hcelih Intf-ii.juon, nl Coni- l-.Rrni, ,n !`I.M,,' \lA,-iui,aurc. 1'incnurM. -A.v1hl.4r.M1n4. |ul,. 1V~4 control group. Further, the possibility was entertained that the inter-' 10 Inlimc, I' F 4" A 1 .t-uu-O.i in me pre, 11 shjf-ir.i, s.. lonek L 'A , tl,--.cn. I' V. Mui-uncl1 l-**,5. 40,' 15 Mum.-i. \ . lUcnwc.. w J \- iun.nl,*i i-"*,Z5, ']** val between the date of inters iew and the date of tetal loss might have influenced the results through dif 15 LenrJ MJ'r\ t.mirunfncr.ui l-r.nevthin Allen*., .umpune *iU enei.ti, 41 mini lot.. ,ub,i,n*e*. u,c m *in*i chlwrtUc. kunireei nu. 6F-,U-5o46 Jn. 50. i:. BFS 005224 --_ .V *# 44 +-- ITEM 3 COPIED BY MCA FOR DISTRIBUTION TO THE VINYL CHLORIDE TECHNICAL PANEL, AUGUST 27, 1976, MR. M. FREIFELD ;,|| 1 \M,1 I. U\V 15, l^.'ft fa) 68 66 64 62 yf 60 e w 58 l56 * 54 62 M 66 68 70 72 Mother E-rosettes (%) Fid, 2--F.-ruictting celt* in ) 3 irt9!bt**beHy pair*. p<0*001, paired t test). For the H-rnsctting ceils the mean for the mothers ups 68-3'r (s,p. 2-Tr) and for the bnbtcs ftl-9 IS.O. ?-7*7). TKs difference trn h Mgnificnnt <p<0.()01} and the correlation coefficient is also significant (r-0-74, r<lM)(l5) (fig. 2). The E ro'fttcv in the mothers ranged from 63*7 to Z24?.^Tc had no counts *4 L'" than 5(Y7 and c;mmu fjnfcnlaitM^fc flic same way as Hnlbruht rod Kore4n^bfc^mir^SByts fortyhtP babies ranged from ^'rvtf^y/i whwh/jTyi^^r than^thcir figures and nearer the mitnsJf 'Sg'rjlcpoftul by Campbell ct aid and Steel r.i at1 There is considerable variation in F-rosettc counts due to technique. We used the method described bv Sticmsw-ird ct al.j In testing each nioih^r and babv's cells together, however, variation due to technique rboul-l not grcatlv jffcct the ratios. `Hie normal range of T cells m newborns >v prnbablv wide. However, our findings ngiy'M that there i< . dirret relation ship between the number of E-rosotiinp cells in some mothers ;nd thetr babies. Since these cells are the m.nor 'uhpopulation f penrheral-hlood lymphocytes, u is likelv that the correla tion between the total Mood-lvmphoeyie counts is largely due ihc correlation between the E-rnscttwg cells , f cellsi. 'Phis raises the possibility that these cell populations m the fetus are regulated by maternal factors. fl4>fh ><11 ('hit.ln-n`k Hippm!, M mhi .m r M9 2AA |\ I. K. F.VANS '-.I l-n I .1.... W 1 I'll * N. VvRAMl'TItr I ll -*rw*t aOll |l^ll H blnitti htuiititr. \\am.Uri<-r MJll VHX M. pM.MfR GF.NHTIC RISKS OF VINYL CHLORIDE Sih,-- Hie iiwcmca in the paper bv I>r infante and his cob leagues April L p 714' that * a sutmt'cant e'v.e**ol tctal loss was observed among vvi\e> folfimmi: rxpoMtr** to \ r m," is siuh as io have instihcd nuuu mo'c tOinpleu presentation. Am avsi rtiuii ot viiJi importanve should at le.isi be vopportv,! Iw a specification of the nicthojs ol Jju mlLwtioii, and a tabu lation ol the r.ivs d.ii.i hrVtc ,m.ilvss [he subiect being spontaneous abortion, the iik of a ques tionnaire, and the cm,imp low response-rates, Can he viewed sympathetically, hut muM detract from the accuracy of the studv. I he data arc prevented onlv alter an age-asiiustnwnt procedure which behaves verv nmlcadmgly A crude percentape of 10-1 {or .1 sample whose average ape t< 2h-4 is .idimicd violently downwards io ft 1, while a figure of 16-5 for a sample of average ape M)-2 is only reduced marginally to 15 X, Pre sumably the adirntnient is being done within the study and the small sample m/c is iIk cause ot inis anomaly It would have been better to have adjusted nil the figures in accordance with national figures, but perhaps*, in such a delicate area, such stat istics are not avail iMc or are unreliable. It is to be hoped that'the complc'c 'tody will be published without delay, with the above omissions rectified, so that it util be possible m put this, at present isolated, question in context. ('rritrjil M.slical Cifroip. ImpcnJl f h^mrej] In luwnrv \Silf7wlu-*. i hrsh-rr Ms* lyit G, M. Psnm t SOCIAL STIGMA AND TUCLRCULOSIS Sir,--You have stated1 that "W ithin the U.K. tuberculosis is no longer feared. It is widely known to be curable with little inconvenience to the patient and u carries little, if any, social stigma". Personal experience in Belfast showed that fear still existed in some patients before their disease was explained to them. Because of thts we have tried to find out if social stigma still exists. XV^jKkrdpTgpmiems with pulmonary tuberculosis and 31 fSaitrwAitPmhcr chf-t diseases of similar ace, sex, and social lW^wind,\fefeout thetr attitudes towards their disease. In the J^bHcrnosis group only 2 of the 13 with a family hisiorv of tuberculosis and 7 of the 19 without such a history knew that it was still possible to develop the disease m Belfast. In fact, there arc at present about 100 new ctwes notified each year in a population of 6C0 000. Only 17 of the 32 patients with tuberculosis knew' that their disease was infectious, 2 university students were among the group who did not know1. A similar proportion thought the dis ease was m xome way related to an inherited, weakness of the chest. Both the tuberculosis group and the control group were asked if they had any <cn<c of shame or similar emotional feel ings became of their illness, 5 of the 31 control pjiu.nis expressed feeling' of inferiority, shame, rmbarrassmont, and a sense of social isolation. I*hc'e were ail related to spctinc physical disabilities such as cough, sputum, or dv<pmra. 12 of the 32 tuberculous patients described feelings of 'hune. in feriority. and a fear of social ostracism None of these jttit tides were related to specific physical complaint'.. The interview with another patient was cancelled due to obvious embarrass ment anJ shame about discussing the disease. An additional 4 from the group of tubcnuloMs patient* although nni suircnng from a direct social stigma about the Jscase expressed a seme of pult and shame at the rclleetton of their life style 'Musi paMerits were male? who had been heovv drinkers with lanulies. although none were alcoholics. Improved social conditions here in the pn<i helped to reduce the incidence of pulmonary tubercu'osi* However, in mans large cities there is uKreavirg alcoholum.\iverv.rowdmi;, squat img, and drug uiVang, as well as an increase m the numbers ot old people. Such features mav nrrc'o the downward trend in noiitr-.'.rmnc nf Thr diMa*c. It the l.wk of knowledge about tuberculosis and the Cuminued 'octal stipmj mu iu*l m vldn b patients exist in other .ueas ot the 1 K then perhap* tm-.v is the time to inere.ive ptblic nliuatior ibnn: a ore*' *nnh! :i,l ' \ 1 H.... . M 1 , Asmlrs l.ni-r: \ \Ut\ < ., t; .. 1*4. |n, 4*<" M . I Mns J . Smi-h, M A 1 ,/*/. s. 14 t Vll.M" m.iiJ. t . 1 ' M , \jnhv. I . Wth'/,a, M , stIi)v, K i+tj {V?:, ,, I t iir Tc IMU.. hi h 4| || i l Ot..u. I'n, Ht RUSTICS DIVISION LIBRARY TRE FIRESTOirE TIKE & RUBBER CO.. foils t.HMi'il'V l td n St \s11ikn 005225