Document ym873E1Mjjr9J7Xz8Ky8Jv5ZX

C-C /^jJsAss*- tfj) C;&ffuc/t /a /? 4 f~}'3r\ oi rr.fr-*^ ^/4^/r Ara Mutanim fU'scvrch. 9p {!9F2) 97- 100 E1sc\icr Biomedical Press RFrr^K~-~ C ,2?^r^55" RECEIVED arr ! 2%2---Sf ICP6H0 I INTERNATIONAL COMMISSION FOR PROTECTION AGAINST ENVIRONMENTAL MUTAGENS AND CARCINOGENS ICPEMC Working Paper TG1 /2 */19 Mutagenicity and teraio^lilcil^.M vijiv] chloride monomer (VCM) ~~ Epidemiological evidence Johannes Clemmesen SiockholmsgaJe 43. 2100 Copenhagen, Denmark (Received 16 Sepiember 1981) (Accepted 21 Sepiember 1981) 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 cholangiocarcinomas. the experience of a British team of histopathologists going over cases from Britain during 1963-1973 has revealed some over-estimate of the 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 the subject of the following review. * It has been agreed to publish this document as a working paper for Task Group 1 of the International Commission for Protection against Environmental Mutagens and Carcinogens (ICPEMC). Toe views expressed are those of the author and do not necessarily represent those of the Commission. They are published to stimulate discussion and comments, which will be welcomed by the author. All correspondence and reprint requests should be addressed to the secretary of ICPEMC: Paul H-M Lehman. Ph. D.. Medical Biological Laboratory TNO. P.O. Box 45. ZZf-0 AA Riiswijk (The Nether lands). Tel. 15-138777. telex 38034 pmtno n) (ICPEMC document 158-1981*13-5) 0165-1110/82/0000-0000/S0175 Elsevier Biomedical Press For Distribution by CMA SPECIAL PROGRAMS DIVJSiC I/&Ref. Me. f% Date f2-- . GTR526 98 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 by Infante (1976) and Infante et al. (1976). The studies were based on data from 4 Ohio communities, of which 3, Ashtabula. Painesville and Avon Lake, had at least 1 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 1960 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 were significant at the P < 0.01 level according to the x2 test- 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 Ridge ville. 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. Pottstown in Pennsylvania and Painesville in Ohio, they compared CNSmalformation rates for white infants bom during 1970-1974 with the rates for white infants in each State, No increase was seen in the Pennsylvania hospital, but an increase, primarily in anencephaly and spina bifida, was noted in the Painesville hospital amounting to 22 cases, or twice the expected. After inspection of the birth-defect registry for Ohio, 1 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 (95confidence 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 Pottstown. Pennsyl vania. and in Painesville. Ohto. revealed no difference between the cases and the controls in possible ex; between the cases and plants. In Kanawha County cases and controls liv association with VCM. In a personal commi among wives of worke without the use of co attempted a comparis* before and after expo number of rubber-factc A total of 95 VCM-pt workers was interviewe Interviews were con pregnancy outcome we was the initial item of a No data were obtained rates for the primary ' separately befor^ted ; It should be ^Bic before analysis findin; misleadingly. From these data pu tion with those of the exposure, the mean pa and for controls 23.0. Because fetal loss i death rates for the pn group. This reduced th Contrarily, the raw for controls was only study group, so that F The asymmetry in paralleled with an asj exposure, numbered ~ 159. respectively, for < Further objections for the plastics indus; based on age prior b adjustment to the co does not justify com;: which requires indepe Therefore, when th so far of an eff|^of GTR 527 ^* ih defects in the as t^fcattempted ed o^rota from 4 .ake. had at least 1 t Lake since 1946. \e 4th community. PVC production. 0 in Avon Lake. Lake increased by mained about the that while the rate 4. the rates in the and Avon Lake, Terences between significant at the aes for malforma- 12 miles from ill-births and live ost of the excess, to North Ridgeoduction with the not uniform and eolleoed through M^^piring Prolenzffion plants, compared CNSthe rates for white 1 hospital, but an in the Painesville ^re case could be ents revealed that ille. However, 2 of ignificantly larger jding housewives) :hance occurrence derate increase in found with vinyl Mtstown. Pennsylthe cases and the ISA 9V controls in possible exposure to VCM. Residential histories showed no difference between the cases and controls when compared at various distances from the PV'C plants. In Kanawha County the author found a difference in the pattern of residents for cases and controls living within 3 miles, but the available data suggested no association with VCM. In a personal communication, Selikoff reported that he had estimated fetal deaths among wives of workers exposed to VCM at 7-14 per 100 pregnancies, although without the use of controls. Referring to this statement. Infante et al.- (1976a) 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 by age. A total of 95 VCM-polymerization workers and 158 rubber and PVC-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 of 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 following observations stand out. Before exposure, the mean paternal age at conception for study pregnancies was 26.4 years and for controls 23.0, with crude fetal death-rates of 10.3 air6.9%, respectively. Because fetal loss is known to increase with increasing parental age, the fetal death rates for the primary VCM exposure group were age-adjusted to the control group. This reduced the rate for the study group, before exposure, from 10.1 to 6.1%. Comrarily. the raw rate, after exposure, of 16.55 for the study group versus 8.8% for controls was only slightly influenced by age adjustment, showing 15.8% for the study group, so that Paddle's objection was fully justified. 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 w ere raised by Downs et al. (1977) in a critical review prepared for the plastics industry. They pointed out 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 Mantel-Haenszels test, which requires independence of the 2 rates being compared, is also found incorrect. Therefore, when the evidence is weighted, it seems that there is ncndejrjonstration so far of an effect of VCM as alleged bv Infante et al. 100 References Baxter. P.J.. P.P. Anthony. Me. Sween et al. (1977) Angiosarcoma of the liver in Great Britain 1963-1973. Br. Med. J.. 2. 919-921. Downs. T.D., R.A. Stallones. R.F, Frankowski et al. (1977) Vinyl Chloride. Birth Defects and Fetal Wastage. The Society of Plastic Industries. 1977. Edmonds. L- (1976) Birth defects and vinyl chloride. Proceed on Women and the Workplace. Conf.. Jan 17-19th. Washington. DC. pp. 114-139, Edmonds. L.D.. H. Falk and J F. Nissim (1973) Congenital malformations and vinyl chloride. Lancet. 2. 1098. Infante. P F- (1976) Oncogenic and mutagenic risks in communities with polyvinyl chloride production facilities. Ann N'.Y. Acad. Sci. 271, 49-57. Infante. P.F.. J.K. Wagoner. Me. Michael et al. (1976a) Genetic risks of vinyl chloride. Lancet. 1, '34-735 and 1289-1290. Infante. P.F., J.K. Wagoner and R.J. Waxweilcr (1976b) Carcinogenic, mutagenic and teratogenic risks associated with vinyl chloride. Mutation Res.. 41. 131-141. Paddle, G.M (1976) Genetic risks of vinyl chloride. Lancet. I, 1079. MUTATION RESEARCH Mutation Research Lett*n publish? considered that the results should < Mutation Research Letters is aiming Manuscripts should not be longer d tables and illustrations. Typeseng acceptance. Contributions--in triplicate--may Research Letters, or directly to th< Dr. R.J Preston. Managing Edito' P.O. Box Y. Oak Ridge, TN 37SJ, Proofs and Reprints Prootreaoing v. acceptance of the paper the subrr artide including the SO free reprir MUTATION RESEARCi Publication schedule for MR is published according to addition, each section has its ow Reg (green), 'regular' volumes: Rev (purple). Reviews in Gene Mutation Research Letters. r----------------------- r -1 Jan. Feb. March April Mav June 1 Julv Aug Sep. Oct. Nov, 1 i 92/1-2 | 93/1 ] 93., 2 94 T 94 7 93 l 93/2 95/3 96/1 96/2 96/3 Total j 5 vols | 13 Vois- 1 92-96 | 92-104 J_ _ _ _ _ _ _ The publication iched In particular, an extra ce ne GTR 529 in