Document MGw52GdYj47VpQO5gBELJ8Nwj

'lI .. Annals New York Academy of Sciences 151. Viola, P. L. 1970. Pathology of vinyl chloride. Med. Lavoro 61i 174. 152. Viola, P. L., A. Dicom A A. Caputo. 1971. Oncogenic response of rat skin, lungs, and bones lo vinyl chloride. Cancer Res. 311 516. 153. Volkheimer, G., F. Szarvas, F. Al Adesie, H. John A S. Wachtel. 1961. Aufsaugung von Polyvinylchlorid-Pulver durch die DUnndarmschleimhaut und deren Abtransport durch die Chylusgefasse. Deut. Gesundheilsw. 16: 1727. . l54r-Vot<-~ ' " ------ -- " _ ^-- -Toxirotuglcal InT|raiUlllLe. damr--T-h -Madurlandsr- 155. Wagner, 11. N., Jr., J. G. McAfee, I. M. Weiner. M. Ilio, J. Martinez A W. P. CaJne, Jr. 1963. The use of Hg-203 labeled bromomercurihydroxypro- pane (BMHP) in radioisotope scanning of the spleen. J. Nucl. Med. 4: 190. 156. Wepler, W. 1971. Zur Morphologie chronischer Leberkrankheilen. Leber Magen Darm 1: 45. 157. Williams, G. M., 1. M. Elliott A 1. 11. Weisdurger. 1973. Carcinoma after malignant conversion in vilro of cpilhelial-like cells from rat liver following exposure lo chemical carcinogens. Cancer Res. 33: 606. -WiLLii'iiia, ft. T. HUP. PtLoweatJao-Mcchanlsms^Xhe-M^tahetism-and Datoxica* - Gltapman vie IJati Ltd. London, England:--" 159. Wilson, R. H. A W. E. McCormick. 1960. Plastics. The toxicily of synthetic resins. A. M. A. Arch. Ind. Health 21: 536. 160. Wilson, R. H., W. E. McCormick, C. F. Tatum <5t J. L. Creech. 1967. Occupa tional acroosteolysis. Report of 3 1 cases. J. Am. Med. Assoc. 201: 577. 161. WiRTSCHAFTER, Z. T. A M. W. Cronyn. 1964. Free radical mechanism for solvent toxicity. Arch. Environ. Health 9: 186. c162. Wittman, 1. 1966, Peritoneoscopy. Vols, 1 A II. Akad6miai KTAfin 63. Zapp, J. A., Jr. viron. Health oxie and health effects of plastics and resin: Pnhlishino Discussion Dr. H. Duchter (University of Cologne, Germany): It would seem belter for statistical investigations on the reported liver function tests if you could compare the results'with similar tests done before the workers came into vinyl chloride manufacturing. Second, in one of the two plants in Germany with incidence of vinyl chloride disease, there is much alcohol intake in the workers. Until now no liver damage has been found. Third, in regard lo low lung-function tests, wc have not confirmed a pathological diagnosis at all. There should be more discussion about the cause of this disease, i.c., whether it is vinyl chloride alone or another agent which may get together with technical vinyl chloride, or vinyl acetate or additives. This -may be important in the causation of angiosarcoma. Last, it has been suggested that liver biopsy be done only after peritoneoscopy because of the risk of bleeding. Dr. M. L. Newhouse: May I ask Dr. L.elbach how he selected his patients and how big was the exposed group he selected them from? Dr. W. K. Lelbach (University of Bonn, Germany): I will begin with the answer to the second part of the question. The whole group is, as far as we know, about ISO workers in this plant. We were alerted in December 1972 by Dr. Veltman's jr.-eve '.hat patients being examined for skin and bone disease also had signs of `Ivor disease. We examined these patients. Later we examined all patients we could bring to the clinic. It is, of course, a selected grooo rod does not permit us to draw conclusions as lo percentages. T009SSK5 B. ExpcrlmcntnI Studies PRELIMINARY STUDIES OF THE FATE C? ':. ^ED VINYL CHLORIDE MONOMER IN R.-C R. E. Hefner, Jr., P. G. Watanabe, and P. J. G enrir.g Dow Chemical U.S.A. Health and Environmental Research Midland, Michigan 48640 Introduction Vinyl chloride monomer (VCM), extensively used for the production of poly vinyl chloride and other plastics, has been associated with the development of angiosarcoma and portal cirrhosis of the liver as well ns other untoward effects in workers exposed to unknown but undoubtedly high concentrations of VCM. Angiosarcomas, zymbnl gland carcinomas, and nephroblastomas developed in rats exposed to concentrations of VCM ranging from 50-10,000 ppm, 4 h/day, 5 days/week for 12 months, and subsequently maintained and observed until death.1 No information is available on the fate of VCM in the mammalian organism at the present time. Such information is essential for elucidating the toxicodynamics of VCM and providing a rationale to assess the potential hazard of exposure to low levels of VCM. Results of preliminary studies on the fate of VCM in rats exposed via inhalation are reported herein. Prior to undertaking these studies we conceived the idea that VCM might be metabolized via the alcohol dehydrogenase pathway, and if so, this pathway would very likely be saturable, and that con jugation of VCM or its metabolites with glutathione and cysteine might be ex pected, Therefore, much of the svork conducted to dale has been directed at evaluating these possibilities. Methods w Kinetic Studies o/ the Uptake (h4elabolism) oj hloride Monomer Male Spraguc-Dawley albino rats of Span g were exposed to initial concentrations of V( ppm (0.13-2.99 mg/liter). Exposures ranged depicts the closed, recirculating 4.7-liter inhala 4 rats were concurrently exposed. To minimi: only the nares of the rats protruded through a ber. Expired carbon dioxide was continuous! absorption on an Ascarite column in the recirc was removed from the system, the pressure manometer fitted with a photoelectric cell. T! dual syringe pump to inject makeup oxygen inti The chamber atmosphere was continuously in-line Miran-1 infrared analyzer (Wilks). Wit. H 10 H nJ 01 01 CO ng from 165-200 rom 50.5-1167.0 3 min. Fioure 1 w which a group of of fur and skin, te into the cham- :0 the chamber by :O ts carbon dioxide :d by a mercury i J> lenoid valve and iro t M (10.9 p) by an trations of VCM * These studies were supported in part by a grant from the Manufacturing Chemists Association. 135 llT S 0 o e0 v5-i- S'S ? S S 5 i C-S* 5! S E .c 8 * S is S3 u53 ^O jg: If!!II 11 m*. IIIP iJ0,,r U} g Wb'-Pi , J> iLlffc^b 2s^ M0Sf-Y sjsjta?3 . e- aa 2 o "Q '3'3*5*S'o'5feta iiw x jj g 'JS CX e +- *h*D gg fc E .25c2 b_se mg e- 5.S a E u 3 <y 11 i o , M g'0',, ? Si m co ^ .5 a ~Ohe VJrSt t3*o>.S_" J*LCa>O 8 ^ 52 . 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