Document ERb4YBdJjrMZ42N73bkwkRGR

R&S 102653 P3104521 *****#************#********************#**#********##* #* * THIS IS AN OFF-LINE BIBLIOGRAPHIC CITATION LIST GENERATED BY #* * MEDLARS II # # N.L.M.'S NATIONAL INTERACTIVE RETRIEVAL SERVICE * # * #* ##**#####*###***#**#*####*******#####*###*##############****#*#*****#* VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED NUMBER OF CITATIONS PRINTED = 74 JANUARY 14, 1988 THIS SEARCH WAS PERFORMED ON THE TOXLIT65 FILE. SORT WAS NOT REQUESTED REQUESTED BY E. GRESCH II E C E I V E D JAN 2 01988 PLEASE SEND THIS LISTING TO UEGAl department DIANE WROBLEWSKI 1803 BUILDING MIDLAND, MICHIGAN 46640 00003178 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 1 R&S 102654 1 AU AD TI SI SO AB 2 AU AU AD TI SI SO AB 3 AU AD TI SI SO AB KRAJEWSKI J ; OOBECKI M ; GROMIEC J Dep. Chemical Air Pollutants Inst. Occupational Mad., Lodz, Poland. Retention of vinyl chloride in the human lung. HEEP/81/09512 BR J INO MED! 37 (4). 1980 (RECD. 1981). 373-374. HEEP COPYRIGHT: BIOL ABS. Experiments with volunteers showed that 42X of an inhaled dose of vinyl chloride (a carcinogen) was retained in the lungs. This value was independent of concentration of vinyl chloride in the air. Elimination of vinyl chloride through the lungs was negligible since its concentration in expired air decreased immediately after cessation of exposure. CORDASCO EM ) DEMETER SL J KERKAY J ) VAN ORDSTRAND HS J LUCAS EV CHEN T ; GOLISH JA 9500 Euclid Ave., Cleveland 44106. Pulmonary manifestations of vinyl chloride and polyvinyl chloride finterstitial lung disease): Newer aspects. HEEP/81/07600 CHEST; 78 (6). 1980 (RECD. 1981). 626-834. HEEP COPYRIGHT: BIOL ABS. Newer varieties of occupational lung diseases primarily due to increased industrial technology were reported. Preeminent among newer agents were vinyl chloride (VC) and polyvinyl chloride. Few cases were reported, only in Europe, with descriptive histopathologic changes. No pathologic studies of VC exposure were described in USA literature. Biopsy abnormalities in patients disclosed desquamation of alveolar macrophages into alveolar lumina and minor interstitial and alveolar inflammatory changes. Pulmonary function abnormalities included restrictive insufficiency. Preventive therapy consisted of avoidance of further exposures, frequent industrial hygiene monitoring and total avoidance of tobacco smoke and associated atmospheric pollutants. No patient had exhibited evidence of pulmonary neoplasm. All 3 patients survived their occupational injuries and 2 were still disabled to varying degrees. Urine and blood levels of phthalic acid derivatives were elevated in 2 patients, exact significance was not fully known. It probably represented a toxicologic response. SMITH AH ; WAXWEILER RJ i TYROLER HA Dep. Community Health, Wellington Clin. Sch. Med., Wellington Hosp. , Wellington 2, N.Z. Epidemiologic investigation of occupational carcinogenesis using a serially additive expected dose model. HEEP/81/07562 AM J EPIDEMIOL! 112 (6). 1980 (RECD. 1981). 787-797. HEEP COPYRIGHT: BIOL ABS. The epidemiologic identification of occupational carcinogens is complicated by several problems including worker mobility between jobs, variation over time of chemicals and processes used, and the long latency period between exposure and discovery of a tumor. Considering these problems, a method using the cumulative dose concept was developed; this 33 102655 00003179 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 2 9 AU AO TI SI SO AB 5 AU AO TI SI SO AB Involves calculating the expected yearly exposure for each cose from work, histories of all noncases close to the case, in year of birth and year of hire. Data required for use of the method include information concerning exposure to the chemicals being studied for each job in each calendar year of the study. Use of the method is illustrated with a study of liver angiosarcoma and vinyl chloride exposure in a polymerisation plant. The value of the method lies in the wealth of information generated concerning the association between chemical exposures and cancer such as exposure level relationships, latency information and the possibility that Z chemicals might be acting independently or jointly. The serially additive expected dose model may prove particularly useful in the analysis of data collected by occupational health surveillance systems, and in retrospective studies. BAXTER PJ ; ANTHONY PP i MACSWEEN R NM ; SCHEUER PJ Employment Ned. Adv. Serv., London NW1 5DT, Engl., UK. Angiosarcoma of the liver.' Annual occurrence and etiology in Great Britain, UK. HEEP/81/0159Q BR J IND MED; 37 (3). 1980. 213-221. HEEP COPYRIGHT: BIOL ABS. The annual occurrence of angiosarcoma of the liver (ASL) in Britain from 1963-1977 was studied, including clinical and occupational details for those cases agreed as ASL by a panel of histopathologists. Cases (28 men, 6 women and 1 infant girl) were agreed as ASL. The increase in the incidence of ASL observed in recent years was attributable to Thorotrast (thorium dioxide) usage (8 cases) and exposure to vinyl chloride (2 cases) in the past. In its clinical presentation and prognosis ASL resembled primary liver carcinoma, except that extrahepatic metatases were found in only 8 (23X) cases, and hemoperitoneum was more common in those cases due to Thorotrast. There is a possible increased risk of ASL in the electrical and plastics fabrication industries, but Information on exposure was inadequate to implicate specific chemicals. The clinical features of 1 case was indicative of As intoxication, but medications in the other patients were not of etiological importance. SUZUKI Y Environ. Sci. Lab., Dep. Community Med., Mt. Sinai Sch. Med., City Univ. N.Y., One Gustave Levy PI., New York, N.Y. 10029, USA. Nonneoplastic effects of vinyl chloride in mouse lung. HEEP/80/09794 ENVIRON RES! 21 (1). 1980. 235-253. HEEP COPYRIGHT-' BIOL ABS. In a previous study, a high incidence of pulmonary tumors (alveologenic neoplasia) in mouse lung exposed to vinyl chloride at heavy dose (2500 and 6000 ppm) for long durations (5 and 6 mo.) wa3 reported (Y. Sucuki). In the present study, nonneoplastic effects in mouse lung were investigated by light microscopy and EM. As major light microscopic alterations, proliferation and hypertrophy of the 00003180 VINYL CHLORIDE. POLYVINYL CHLORIDE / CANCER-RELATED PAGE 3 terminal bronchiolar cells, consisting of ciliated and Clara cells, hypersecretion of the epithelial mucin in the goblet cells of both the bronchial and the proximal bronchiolar epithelium, hyperplasia of alveolar epithelium, mobilisation of alveolar macrophages and occasional presence of peribronchial or bronchiolar chronic inflammation, were observed. Electron microscopically. Clara cells of the terminal bronchiolar epithelium showed proliferation of the rough and smooth surfaced endoplasmic reticulum and appearance of large and abnormally shaped mitochondria. Similar alterations were found in the ciliated cells. Submicroscopic changes of pulmonary alveoli were represented by focal thickening of the basement membrane, multiple foci of hyperplastic type II cell (the precondition of the alveologenic tumor), active discharge of osmiophilic lamellar bodies from the type II cell and phagocytosis of the bodies by macrophages, appearance of cholesterol crystalloids in the macrophages. degeneration of alveolar septal cells and occasional appearance of a large nucleus with swelling of the capillary endothellum. 6 AU - MURATOV MM ; TAKHIROV MT TI - MAXIMUM PERMISSIBLE CONCENTRATION OF VINYL CHLORIDE IN AIR SI - HEEP/81/09115 50 - GIG SANIT; 0 (11). 1979 (RECD. 1980). 74-76. LA - RUS AB - HEEP COPYRIGHT: BIOL ABS. NOTE HUMAN RAT CARCINOGEN RNA IMMUNITY MUTAGENICITY TEMPERATURE LIVER KIDNEY BRAIN HEART OCCUPATIONAL HEALTH 7 AU - PIALAT J ! PASQUIER B ! PHAN M 5 KOPP N AD - Lab. Anat. Pathol., Cent. Hosp. Univ. Lyon, Fac. Alexis Carrel, rue Guillaume-Paradin. 69372 Lyon Cedex 2, Fr. TI - Hepatic lesions caused by vinyl chloride monomer in humans: 8 cl inicopathological cases. 51 - HEEP/80/10961 50 - ARCH ANAT CYTOL PATHOL! 27 (6). 1979 (RECD. 1980). 361-375. AB - HEEP COPYRIGHT: BIOL ABS. Sixhepatic angiosarcomas, 1 hepatoma and 1 hepatic fibrosis with portal hypertension in patients chronically exposed to vinyl chloride monomer (VCM) are reported. The industrial methods of synthesis and current knowedge on the carcinogenic role of VCM are reviewed. Histogenetic and pathogenetic concepts of fibrosis and angiosarcomas of liver are discussed. 8 AU - 0AVIS DL ! MAGEE BH TI - CANCER AND INDUSTRIAL CHEMICAL PRODUCTION 51 - HEEP/80/10250 SO - SCIENCE (WASH D C)i 206 (4425). 1979 (RECD. 1980), 1356, 1358. LA - ENG AB - HEEP COPYRIGHT: BIOL ABS. NOTE HUMAN BENZENE PER CHLOR ETHYLENE VINYL CHLORIDE ACRYLONITRILE ASBESTOS CHROMITE CHLOROFORM CARBON TETRA CHLORIDE TRI CHLOROETHYLENE CARCINOGEN LUNG CANCER SMOKING R&S 102656 R&S 102657 ii 00003161 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 4 9 AU AO TI SI SO AB 10 AU AD TI SI SO AB FERON VJ ; SPIT BJ ; IMMEL HR ; KROES R Oep. Toxicol., Cent. Inst. Nutr., P.O. Box 360, 3700 AJ Zeist, Neth. 1-year time-sequence inhalation toxicity study of vinyl chloride in rats: 3. Morphological changes in the liver. HEEP/80/06359 TOXICOLOGY; 13 (2). 1979. 143-154. HEEP COPYRIGHT: BIOL ABS. Wistar rats were exposed to atmospheres containing 0 (control) or 5000 ppm vinyl chloride monomer (VCM), 7 h/day, 5 days/week, for 52 wk. After 4, 13, 26 and 52 weeks each time 10 rats/sex per group were killed and subjected to extensive examinations. The morphological changes found in the liver were described. The major parenchymal changes comprised swelling and malformation of mitochondria, an increased amount of smooth endoplasmic reticulum, necrosis, nuclear and cellular polymorphism of hepatocytes, foci of cellular alteration, neoplastic nodules and hepatocellular carcinomas. A reduced glucose-6-phosphatase activity in hepatocytes and a strong sinusoidal activity of alkaline phosphatase were found within foci of cellular alteration. The non-parenchymal alterations included focal dilatation of sinusoids, focal proliferation of atypical sinusoidal cells and multicentric angiosarcomas. The effects of VCM on the hepatic parenchyma seemed to precede those on the hepatic stroma. FERON VJ ; KROES R Dep. Toxicol., Cent. Inst. Nutr., P.O. Box 360, 3700 AJ Zeist, Neth. 1-year time-sequence inhalation toxicity study of vinyl chloride in rats: 2. Morphological changes in the respiratory tract, ceruminous glands, brain, kidneys, heart and spleen. HEEP/60/06358 TOXICOLOGY; 13 (2). 1979. 131-142. HEEP COPYRIGHT: BIOL ABS. Wistar rats were exposed to atmospheres containing 0 (control) or 5000 ppm vinyl chloride monomer (VCM), 7 h/day, 5 days/wk, for 52 wk, After 4, 13, 26 and 52 wk each time 10 rats/sex per group were killed and subjected to extensive examinations. The morphological changes observed in the respiratory tract, ceruminous glands, brain, kidneys, heart and spleen were described. The VCM-effects included increased degree of tubular nephrosis, mild focal degeneration of the myocard and increased hematopoietic activity in the spleen. Primary tumors were found in the brain (ependymoma), lungs (papillary adenoma and mesenchymal type of tumor), ceruminous glands (mainly keratinized squamous cell carcinomas), and nasal cavity (carcinomas of the olfactory epithelium, carcino-sarcoma, es thesioneuroepithelioma ). 00003182 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 5 11 AU AD TI SI SO AB 12 AU TI SI SO AB 13 AU AD TI SI SO AB GEHRING PJ ! WATANABE PG ; PARK CN Toxicol. Res. Lab., Dow Chem. USA, Midland, Mich. 48640, USA. Risk of angiosarcoma in workers exposed to vinyl chloride as predicted from studies in rats. HEEP/80/01556 TOXICOL APPL PHARMACOL; 49 (1). 1979. 15-22. HEEP COPYRIGHT: BIOL ABS. Dose-response data for the induction of angiosarcoma in rats exposed to various levels of vinyl chloride (VC) together with attendant biotransformation data were used to estimate the risk of developing angiosarcoma in persons exposed to VC. Since a biotransformation product of VC, not VC per se, is responsible for the induction of angiosarcoma, the body surface area of people relative to rats was used to estimate the dose of the carcinogen biotransformed from VC by the former. Four models were used to extrapolate the data. Using a probit modal, 10 hepatic angiosarcomas were predicted to occur in a recently reported epidemiological cohort of 9677 workers whereas 5 have occurred. Linear models and that based on the equation, Risk = 1 - e-betax, where x = dose, do not appear as reliable. For an 8 h day, 5 days/wk, 35 yr time-weighted/average exposure of 1 ppm, the predicted incidence of hepatic angiosarcoma using the probit model is 1.5 HALEY TJ CHL0R0PRENE 2 CHL0R0-1 3 BUTADIENE WHAT IS THE EVIDENCE FOR ITS CARCINOGENICITY HEEP/79/13416 WINEK, CHARLES L. AND SYDNEY P. SHANOR (ED.). TOXICOLOGY ANNUAL, VOL. 3. XII+340P, ILLUS. MARCEL DEKKER, INC.: NEW YORK, N.Y., USA; BASEL, SWITZERLAND. ISBN 0-8247-6773-X.J 1979 153-170 HEEP COPYRIGHT: BIOL ABS. HUMAN RAT MOUSE NERVOUS SYSTEM VINYL CHLORIDE CARCINOGEN OCCUPATIONAL EXPOSURE MIXED FUNCTION OXIDASE NERVOUS SYSTEM EFFECTS LUNG CANCER SKIN CANCER DENTAL EFFECTS ZUCCATO E ; MARCUCCI F ; FANELLI R ! MUSSINI E 1st. Ric. Farmacol. Mario Negri, Via Eritrea 62, 20157 Milan, Italy. Head-space gas-chromatographic analysis of vinyl chloride monomer in rat blood and tissues. HEEP/79/12436 xenobiotica; 9 m. 1979. 27-32. HEEP COPYRIGHT: BIOL ABS. A method for measuring (the carcinogen) vinyl chloride monomer (VCM) concentration in rat blood and tissues is described, using a head-space GLC technique with flame ionization detector. The method is sensitive to 5 ng/ml VCM in blood and 30 ng/g in tissues. VCM disposition was determined in rat blood, liver, kidney, brain and lung at different intervals after administration of 1-10 mg VCM/kg l.v. and 10 mg/kg orally. VCM distributed rapidly in the organism after i.v. administration; it was eliminated rapidly and was no lonqer detectable at 15 min for the highest dose and at 4 min for the lowest. VCM was absorbed rapidly when given orally and tissue R&S 102658 i* 00003183 VINYL CHLORIDEi POLYVINYL CHLORIDE / CANCER-RELATED PAGE 6 R&S 102659 concentrations were measurable for longer than after i.v. treatment. For both routesi VCM concentration in liver and lung decrease faster than in other organs> suggesting that these organs play a role in VCM elimination. 14 AU - BUFFLER PA ; WOOD S J EIFLER C ! SUAREZ L ; KILIAN DJ AD - Univ. Tex. Sch. Public Health, P.O. Box 0186, Houston, Tex. 77025, USA. TI - Mortality experience of workers in a vinyl chloride monomer product plant. SI - HEEP/79/10829 SO - J OCCUR MED! 21 (3). 1979. 195-203. AB - HEEP COPYRIGHT: BIOL ABS. The evidence associating exposure to vinyl chloride with the risk of tumors of various sites, including lung cancer, is inconsistent. In 1976 a mortality follow-up study of 464 white males employed in a vinyl chloride monomer (VCM) production plant since 1948 was conducted. Vital status was ascertained for 100'/. of the cohort. Of the 28 deaths observed, 8 (28.5/.) were due to malignant neoplasms. No angiosarcomas or other liver tumors were observed. A statistically significant excess was noted for malignant neoplasms of the respiratory system (P = .03). The effect of smoking, duration of exposure to VCM, level of exposure and the combined effect of duration and level of exposure were analysed separately. A 5-yr latency requirement was maintained for all analyses except for the smoking analysis. Levels of exposure to VCM prior to 1971 were estimated from monitoring data available for the period 1971-1975 by extrapolating the relative levels for job classifications backwards in time. Smoking histories were not available for 21.6/. of the cohort. When it was assumed that all "unknowns" smoked, a significant excess of respiratory cancer was still observed (P = .05). When the minimum latency period of 5 yr restricted analysis to the mortality experience after 5 yr from date of initial exposure to VCM for the 314 employees satisfying this criterion, the excess of respiratory cancer was moderate but not significant (P = .06). Both a longer duration and a higher level of exposure during the first 5 yr following the date of initial exposure were associated with a statistically significant excess of respiratory cancer (P = .02 and .03, respectively). When duration and level of exposure were combined in an overall exposure index, the results were not significant (P = .07). The discrepancy in the results from the dose-response analyses may be due to the potential error in the estimated levels and the small number of events observed, but the results suggest that a relationship exists between exposure to VCM and respiratory cancer. 00003184 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 7 R&S 102660 15 AU - CHEN K TK ; BOLLES JC ; GILBERT EF AO - Oep. Pathol., Fresno Community Hosp., P.O. box 1E32, Fresno, Calif. 93715, USA. TI - Angiosarcoma of the spleen: A report of two cases and review of the 1iterature . SI - HEEP/79/09598 SO - ARCH PATHOL LAB MED; 103 131. 1979. 122-124. AB - HEEP COPYRIGHT: BIOL ABS. Ultrastructural study of 1 of 2 cases of splenic angiosarcoma established the blood vessel origin of this tumor. Previously reported cases f53) were reviewed. None of the 55 patients had a history of exposure to thorium dioxide, vinyl chloride or As, which are known to be associated with hepatic angiosarcoma and other tumors. A comparison of the splenic and hepatic angiosarcomas showed that tumors not associated with exogenous material frequently involve the spleen and liver simultaneously. Tumors associated with thorium dioxide, vinyl chloride, or As commonly involve the liver with sparing of the spleen. 16 AU - Bartsch H i Sabadie N ; Malaveille C ; Camus AM AU - Richtei--Reichhelm HB AD - Unit Chem. Carcinog., Int. Agency Res. Cancer, Lyon TI - Carcinogen metabolism with human and experimental animal tissues-' intei--individual and species differences SI - CA/093/001946V SO - Adv. Med. Oncol., Res. Educ., Proc. Int. Cancer Congr., 12th; VOL 3,, 1979,179-87 LA - ENG AB - CBAC COPYRIGHT: CHEM ABS Liver fractions obtained from surgery tissue samples of different human subjects were shown to convert vinyl chloride or related haloolefins and several N-nitroso derivs. into alkylating and mutagenic intermediates. (75-01-4 Vinyl chloride) Although large individual' variations were obsd., the av. activity was lower or close to mouse or rat liver fractions. However, with N-nitroso-N'-mefhylpiperazine, human liver samples were up to 40 times more active than rat liver. When hepatic benzoCaJpyrene hydroxylase (BP hydroxylase) activity in samples from different human subjects wa3 plotted against the liver microsome-mediated mutagenicity, a pos. correlation was obtained between the rates of oxidative BP metab. and mutagenicity in the presence of N-nitrosomorpholine or vinyl chloride as substrate. (16339-07-4 N-Ni troso-N'-methylpiperazine )(9037-52-9 benzo Ca)pyrene hydroxylase)(59-89-2 N-Nitrosomorpholine) Therefore, BP hydroxylase activity in normal and tumorous lung tissue from 76 patients with lung tumors was measured. A 60-fold interindividual variation was noted with the rates of BP hydroxylation in tumorous lung tissue lower than in normal tissue of the same patient. When BP hydroxylase activity in the tumorous tissue was plotted vs. the no. of cigarets smoked per day prior to surgery, a neq. correlation was apparent. Thus, differences m carcinogenic metab. may condition in part the R&S 102661 00003165 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 8 17 All AU AO TI SI so LA AB 18 AU AO TI SI SO LA AB 19 AU AO TI SI SO LA AB response of human individuals when exposed to the same level of environmental carcinogens. Brundrett RB ; Colvin M ; White EH ; McKee J i Hartman PE Brown 0L Dap. Chem., Johns Hopkins Univ., Baltimore Comparison of mutagenicity, antitumor activity, and chemical properties of selected nitrosoureas and nitrosoamides CA/091/032798M Cancer Res.! VOL 39, ISS 9, 1979,1328-33 ENG CBAC COPYRIGHT: CHEM ABS Nitroureas and nltrosoamides were compared with respect to mutagenicity for Salmonella typhimurium, in vitro cytotoxicity, in vitro toxicity and antitumor activity against murine leukemia, and chem. properties. Despite chem. similarities between the nitroureas and nitrosoamides, they showed important differences in biol. activity. Some of the nitrosoureas were very active antitumor agents, and less mutagenic than the corresponding nitrosoamides, which lacked antitumor activity. Feron VJ ; Kroes R Cent. Inst. Nutr, Food Res., TNO, Zeist One-year time-sequence inhalation toxicity study of vinyl chloride in rats. II. Morphological changes in the respiratory tract, ceruminous glands, brain, kidneys, heart and spleen CA/092/01686OR Toxicology; VOL 13, ISS 2, 1979,131-91 ENG CBAC COPYRIGHT: CHEM ABS Rats were exposed to atms. contg. 0 (control) or 5000 ppm vinyl chloride monomer (VCM), 7 h/day, 5 days/wk, for a period of 52 wk. (75-01-9 Vinyl chloride) After 9, 13, 26 and 52 wk 10 rats/sex/group were killed and subjected to extensive examns. VCM-induced effects included an increase in the degree of tubular nephrosis, mild focal degeneration of the myocardium, and increased hematopoietic activity in the spleen. In addn. , primary tumors were found in the brain (ependymoma), lungs (papillary adenoma and mesenchymal-type of tumor), ceruminous glands (mainly keratinized squamous cell carcinomas), and nasal cavity (carcinomas of the olfactory epithelium, carcinosarcoma, and esthesloneuroepithelioma). Feron VJ ! Spit BJ i Immel HR ; Kroes R Cent. Inst. Nutr. Food Res., TNO, Zeist One-year time-sequence inhalation toxicity study of vinyl chloride in rats. III. Morphological changes in the liver CA/092/016616R Toxicology; VOL 13, ISS 2, 1979,193-59 ENG CBAC COPYRIGHT: CHEM ABS Rats were exposed to atmospheres contg. 0 (control) or 5000 ppm vinyl chloride monomer (VCM), h/day, 5 days/wk, for a period of 52 wk. (75-01-9 Vinyl chloride) After 9, 13, 26 and 52 wk 10 rats/sex/group were 7 11 00003186 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 9 R&S 102662 killed and subjected to extensive examns. The major parenchymal changes comprised swelling and malformation of mitochondria, an Increased amt. of smooth endoplasmic reticulum, necrosis, nuclear and cellular polymorphism of hepatocytes, foci of cellular alteration, neoplastic nodules and hepatocellular carcinomas. A reduced glucose 6-phosphatase activity in hepatocytes and a strong sinusoidal activity of alk. phosphatase were found within foci of cellular alteration. (9001-78-9 Alkaline phosphatase )(9001-78-9 alk. phosphatase) The nonparenchymal alterations included focal dilation of sinusoids focal proliferation of atypical sinusoidal cells and multicentric angiosarcomas. The effect of VCM on the hepatic parenchyma seemed to precede those on the hepatic stroma. 20 AU - DAHL GA ; MILLER JA ; MILLER EC A0 - McArdle Lab. Cancer Res., Univ, Wis. Cent. Health Sci., Madison, Wis. S3706, USA. TI - Vinyl carbamate as a promutagen and a more carcinogenic analog of ethyl carbamate. SI - HEEP/79/05120 50 - CANCER RES! 38 ((11 PART 11). 1978 3793-3804 AB - KEEP COPYRIGHT: BIOL ABS. Vinyl carbamate was much more active (10 to 50 times) than ethyl carbamate for the initiation of skin tumors and for the induction of lung adenomas in mice. Vinyl carbamate was also mutagenic to Salmonella typhimurium TA 1535 and TA 100 in the presence of NAOPH-fortified rat or mouse liver mitochondrial supernatant fractions. This mutagenic activity was inhibited strongly by cytochrome P-450 inhibitors. No mutagenic activity was observed for vinyl carbamate in the absence of added liver preparations or for ethyl carbamate in the presence or absence of liver fractions. Extensive tests with sensitive methods failed to detect vinyl carbamate as a metabolite of ethyl carbamate in the mouse in vivo. However, on administration of (ethyl-1- 14C;1,2-3H )ethyl carbamate to adult mice the 3H/14C ratios of the hepatic DNA-, rRNA-, and protein-adducts were similar to each other and much lower than the ratio of the administered ethyl carbamate. These data are consistent with the presence of desaturated and/or oxidised ethyl groups in the macromolecular adducts. The qualitatively similar, but much stronger, carcinogenic activity of vinyl carbamate as compared to that of ethyl carbamate suggests that the metabolic pathways of these two carbamates may converge in the formation of similar or identical electrophilic reactants that bind covalently to macromolecules in vivo and initiate carcinogenesis. 21 AU - DELORME F ! THERIAULT G A0 - Oep. Pathol., Cent. Hosp. Reg. Maurice, Shawinigan, Que., Can, TI - Ten cases of angiosarcoma of the liver in Shawinigan, Quebec. 51 - HEEP/79/03983 SO - J OCCUR MED; 20 (5). 1978 338-340 AB - HEEP COPYRIGHT: BIOL ABS. Ten cases of angiosarcoma of the liver have been diaqnosed in Shawinigan, Quebec (Canada) since 1955. All have occurred in men who worked in a vinyl chloride 3 00003X87 VINYL CHLORIDE, POLYVINYL CHLORIOE / CANCER-RELATED PAGE 10 polymerising plant. Cigarettes and alcohol did not seem to be associated with this tumor. The amount of vinyl chloride to which these people were exposed, according to information obtained through questionnaires, appears elevated. Angiosarcoma of the liver was accompanied by a fibrosis of the liver which may precede its appearance. In describing the Canadian cases of angiosarcoma, this study attempted to shed more light upon the causal relationship between vinyl chloride monomer and angiosarcoma of the liver and to provide some clues to understanding the pathogenesis of this disease. 22 AU - DELORME F AD - Cent. Hosp. Reg. Mauricie, CP 1130, Shawinigan-Sud, Due., Can. TI - Association of angiosarcoma of the liver with hepatoma in a vinyl chloride worker. SI - HEEP/79/03980 SO - ANN ANAT PATHOL; 23 (2). 1978 105-113 AS - HEEP COPYRIGHT: BIOL ABS. This report deals with a 51 yr-old man who, for 23 yr and 9 mo. of his working life, was exposed to vinyl chloride vapors. Autopsy revealed a hepatoma associated with an angiosarcoma of the liver. The case is the 1st ever to be reported in the medical litterature. This case raises doubts about the theory which suggests that the carcinogenic effect of vinyl chloride in man elicit a tumor of vascular nature. 23 AU - VAN 0UUREN BL ; LOEWENGART G ; SEIDMAN I ; SMITH AC ! MELCHIONNE 5 AO - Lab, Org. Chem. Carol nog., Inst. Environ, Med., N.Y. Univ. Med. Cent., New York, N.Y. 10016, USA. TI - Mouse skin carcinogenicity tests of the flame retardants tris(2,3--dibromopropyl Iphosphate > tetrakisfhydroxymethyl Jphosphonium chloride, and polyvinyl brom1de. SI - HEEP/79/03540 SO - CANCER RES', 38 (10). 1978 3236-3240 AB - HEEP COPYRIGHT: BIOL ABS. The flame retardants tris(2,3-dibromopropyl Iphosphate, tetrakls(hydroxymethyl Iphosphonlurn chloride and polyvinyl bromide were tested for carcinogenic activity by skin application 3 times weekly in random-bred female ICR/Ha Swiss mice for 420-496 days. Tris(2,3-dibromopropyl Iphosphate at 2 dose levels (30 and 10 mg/application) induced beniqn and malignant tumors of the skin, forestomach and oral cavity (tongue and gingiva) in a statistically significant number of mice (30/group). A statistically significant incidence of papillary tumors of the lung was observed at both dosages. One carcinoma of the liver was observed at both doses, and the higher dose also resulted in 1 mouse with a tubular adenoma of the kidney. Tetrakis(hydroxymethylJphosphonlurn chloride (2 mg/application, 60 mice) and polyvinyl bromide (0.1 ml latex suspension/appl1 cation> 30 mice) were inactive. Polyvinyl bromide was also injected s.c. into another group of female ICR/Ha Swiss mice once weekly for 48 wk, and the mice were observed for a total of 60 wk. Liposarcomas were induced in 19 of 30 mice, which was ascribed to physical R&S 102663 R&S 102664 00003188 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 11 carcinogenesis. Appropriate solvent and no-treatment control groups were included. 24 AU - WATANABE PG ; ZEMPEL JA ; PEGG DG 5 GEHRING PJ AD - Toxicol. Res. Lab., Health Environ. Res., 1803 Build., DowChem. Co., Midland, Mich. 48640, USA. TI - Hepatic macromolecular binding following exposure to vinyl chloride. SI - HEEP/79/027I7 50 - TOXICOL APPL PHARMACOL; 44(3). 1978 571-580 AB - HEEP COPYRIGHT: BIOL ABS.Covalent binding of radioactivity to hepatic macromolecules in rats exposed to 14C-labeled vinyl chloride (VC) was studied to determine if VC-induced carcinogenesis may be related to electrophilic alkylation of macromolecules in vivo. Male Sprague-Oauley rats were exposed to 1, 10, 25, 50, 100, 250, 500 or 5000 ppm of (14C1VC for 6 h. Following exposure, radioactivity covalently bound to hepatic macromolecuies and purified nucleic acids (RNA, DNA) was determined. The total amount of (14CJVC metabolized and hepatic glutathione (GSH) content were also determined. The total amount of radioactivity bound to macromolecuies in the liver did not increase proportionately to the increase in the exposure concentration of VC. A disproportionate decrease in macromolecular binding was observed as the concentration of VC increased. Covalent binding to hepatic macromolecuies was related to the amount of VC metabolized. At exposures greater than 50 ppm, the amount of 14C bound to macromolecuies in the liver correlates with induction of hepatic angiosarcoma. There was no detectable binding of radioactivity to DNA or RNA in the liver. Hepatic glutathione content was significantly depressed only at exposure concentrations greater than 100 ppm. 25 AU - POPPER H ; THOMAS LB ! TELLES NC ; FALK H ; SELIKOFF IJ AO - Lab. Pathol., Natl. Cancer Inst., Room 2A27, Build. 10, Bethesda, Md. 20014, USA. TI - Development of hepatic angiosarcoma in man induced by vinyl chloride, Thorotrest, and arsenic: Comparison with cases of unknown etiology. 51 - HEEP/79/02712 SO - AM J PATHOL; 92 (2). 1978 349-376 AB - HEEP COPYRIGHT: BIOL ABS. Examples of human angiosarcoma following exposure to vinyl chloride, Thorotrast or As (medicinal and industrial) and cases, including children, of unknown etiology were studied to establish diagnostic criteria and to study their evolution. The uniform evolution suggests an environmental factor also in the cases of unknown etiology, which may be established by epidemiologic studies. A precursor stage is characterized by areas of combined hyperplasia of hepatocytes and a variety of sinusoidal and perisinusoidal cells associated with excess of reticulin and sinusoidal dilatation. The diagnostically useful picture in Ag impregnations indicates reticulum formation by the perisinusoidal cells, presumably the lipocytes. The hepatocytic proliferation suggests a hepatocarcinogenic but dl 00003189 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 12 usually not fully expressed potential. The mixed hyperplasia of the various sinusoidal cells proceeds to an overgrowth of angiosarcoma cells, presumably derived from endothelial cells. In early stages they are usually in contact with hepatocytes (intralobular growth). A trabecular arrangement results from loosening of the lobular plate arrangement by dilatation of sinusoids, leading to primary peliosis. With disappearance of the hepatocytes, various growth patterns develop, terminating in nodular, solid angiosarcoma composed of spindle-shaped or polyhedral cells which undergo necrosis or hemorrhage (secondary peliosis). The interaction between hepatocytes and sinusoidal cells requires elucidation. 26 AU - SUZUKI Y AD - Environ. Sci . Lab., Mt. Sinai Sch. tied.. Fifth Ave. and 100th St., New York, N.Y. 10029, USA. TI - Pulmonary tumors induced in mice by vinyl chloride monomer. SI - HEEP/79/02364 SO - ENVIRON RES) 16 (1-3). 1978 285-301 AB - HEEP COPYRIGHT: BIOL ABS. Neoplastic effects of vinyl chloride were studied in lunqs of 27 mice exposed to vinyl chloride monomer at 2500 and 6000 ppm for 5 and 6 mo. Pulmonary tumors were observed in 26 of 27 experimental animals. By light microscopy, the tumors were multiple and arranged in either tubulo-papillary or adenomatous formations. Although occasional mitotic divisions and invaginations into the broneniolar lumen were observed, no metastases were found. By EM, short microvilli, tight junctions between 2 adjacent cells, appearance of osmiophilic lamellar bodies, large mitochondria of irregular shape, well-developed Golgi complexes, continuous or discontinuous basement membranes, occasional appearance of sequestration and of crystalloids, and lack of both cilia and mucous secretory granules were observed as characterlstic features of the neoplastic cells. Some of the cells were poorly differentiated and Were equipped with poorly developed organoids, without formation of osmiophilic lamellar bodies. The pulmonary tumors corresponded to alveologenic tumors or alveologenic cancer. The neoplastic cells were probably transformed from type II alveolar epithelium via its hyperplastic form. Mouse lung is an extremely sensitive indicator of the oncogenicity of vinyl chloride. _ 27 AU - TAMBURRO CH AD - Dig, Dis. Nutr. Div., 511 S. Floyd St., PO Box 35260, Louisville, Ky. 40232, USA. TI - The hepatic role in carcinogenesis and its early detection: The vinyl chloride model. SI - HEEP/79/00115 SO - YALE J BIOL MED! 51 (1). 1978 67-80 -- AB - HEEP COPYRIGHT: BIOL ABS. The liver's role in vinyl chloride toxicity and carcinogenicity is providing a better understanding of the chemical carcinogenesis mechanism, A variety of malignant and benign hepatic tumors was demonstrated with prolonged R&S 102665 \ 00003X90 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 13 R&S 102666 exposure to vinyl chloride. The multisystem involvement of this carcinogen and toxin provided a model for the study of chemical carcinogenesis common to man and animal. Clinical studies showed the usefulness of biochemical, radioisotopic and radiological studies in the detection of toxic and carcinogenic lesions. An lmal studies demonstrated the biochemical metabolism by the liver of vinyl chloride-produced intermediates which are mutagenic in bacterial systems and may be the ultimate carcinogens. Hepatic subcellular enzyme studies prove preliminary evidence of cellular adaptation and increased detoxification. Disruption of this oxidization and detoxification balance may be the key to malignant transformation of cells. A working hypothesis is presented which may explain the metabolism of vinyl chloride into mutagenic intermediates by liver cells and the development of malignant transformation by extrahepatic sinusoidal lining cells, lung cells and brain tissue. 28 AU - LEE CC ; BHANDARI JC ; WINSTON JM ; HOUSE WB ! DIXON RL ; WOODS JS AD - Midwest Res. Inst., 425 Volker Blvd., Kansas City, Mo. 64X10, USA. TI - Carcinogenicity of vinyl chloride and vinylidene chloride. SI - HEEP/73/10445 50 - J TOXICOL ENVIRON HEALTH; 4 (1). X978 15-30 AB - HEEP COPYRIGHT: BIOL ABS. Exposure of mice to 50, 250 or 1000 ppm of vinyl chloride (VC) in the air for 6 h/day, 5 days/wk, caused a high incidence of bronchioloalveolar adenoma, mammary gland tumors and hemangiosarcoma. Mammary gland tumors occurred in females and included ductular adenocarcinoma and squamous and anaplastic cell carcinomas with metastases to the lungs. Hemangiosarcoma occurred in the liver and, to a lesser extent, in various other organs. The incidence and severity of these tumors increased with the concentration of VC and length of exposure. Malignant lymphoma involving various organs was observed in several mice. Rats were more resistant to the carcinogenic effects of VC. Exposure of rats to 250 or 1000 ppm of VC caused hemangiosarcoma in the liver. Many rats with hepatic hemangiosarcoma also developed hemangiosarcoma in the lung. Extrahepatic hemangiosarcoma also occasionally occurred in other organs. Exposure to 55 ppm of vinylidine chloride (VDC) caused hepatic hemangiosarcoma and probably bronchioloalveolar adenoma in mice. Hemangiosarcoma also occurred in the mesenteric lymph node or subcutaneous tissue in 2 rats exposed to 55 ppm of VDC. 29 AU - Milby TH A0 - 5RI Int., Menlo Park TI - Vinyl chloride - on information resource 51 - CA/092/081459F SO - Report; ISS NIH-78/1599, OHEW/PUB/NIH-78/1599; Order No. HRP-0028012,, 1978,122pp. LA - ENG AB - CBAC COPYRIGHT: CHEM ABS A discussion of the link between exposure to vinyl chloride (I) and the occurrence of toxic, nonmalignant illnesses involving skin, bones, liver, lungs, and blood is provided. (75-01-4 Vinyl chloride) The regulatory 00003191 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 14 history of I 13 outlined. The potential for human contact with I is great. About 2.5 billion kg of I are produced each year in the United States. I is produced at 15 plants employing 900 workers. I is also polymd. at 39 plants, employing more than 5,500 workers. The Environmental Protection Agency has estd. that approx. 5 million people live near enough to I facilities to be within range of detectable airborne concns. of the gas. The prodn., uses, and dispersion of I are discussed, evidence of its toxic and carcinogenic effects are summarized, and strategies for its control are suggested. The appendices contain a list of I-related compds., an approach to evaluation and control of I exposure, and sources for addnl. information. 30 AU - Costa V ; Frongia N AD - Univ. Cagliari, Cagliari TI - Histological and ultrastructural study of the peritoneal changes induced by the endoabdominal inoculation of a single dose of polyfvinyl chloride) powder (PVC) in rats SI - CA/091/152238A 50 - Rass. Med. Sarda; VOL 81, ISS 4, 1978,217-35 LA - ITA AB - CBAC COPYRIGHT: CHEM ABS In rats i.p. administration of PVC resulted in granulomas of the peritoneum, (9002-86-2 Poly(vinyl chloride)) No neoplastic or preneoplastic alterations were obsd. Histopathol. changes of the lung, liver, and spleen, were also obsd. 31 AU - Anderson HA ; Snyder J ; Lewinson T ; Woo C ; Lilis R AU - Selikoff IJ AD - Mt. Sinai Sch. Med., City Univ. New York, New York, N. Y. TI - Levels of CEA among vinyl chloride and poly(vinyl chloride )-exposed workers 51 - CA/090/043308G SO - Cancer (Philadelphia); VOL 42, ISS 3, Suppl,, 1978,1560-7 LA - ENG AB - CBAC COPYRIGHT: CHEM ABS In 1974, vinyl chloride (VC) exposed workers had an increased risk of malignant disease (hemangiosarcoma of the liver), (75-01-4 Vinyl chloride) Thus 1147 workers exposed to VC monomer in 3 VC/poly(vinyl chloride) (PVC) . plants and 269 workers from a PVC extrusion plant manufg. PVC textile product, exposed to much lower concns. of VC were examd. (9002-66-2 Poly(vinyl chloride)) Included among the comprehensive clin. and lab. studies conducted was the CEA (carelnoembryonic antigen) titer. The investigation demonstrated that occupational exposures in VC/PVC plants can cause elevations in the CEA titers of otherwise healthy individuals. Prospective follow-up is necessary before conclusions can be drawn concerning the usefulness of the CEA titer as a predictive indicator of possible increased risk. R&S 102667 R&S 102668 00003192 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE IS 32 AU - Wine 11 M Holmberg B ; Kronevi T AO - Unit Oceup. Toxicol., Natl. Board Occup. Saf. Health, Sued. TI - A possible correlation between biochemical changes and pathological findings in VCM-exposed mice and hamsters SI - CA/090/034611Y SO - Int. Symp, Control Air Pollut. Work. Environ., [Proc.1I VOL Part 1,, 1973,152-66 LA - ENG AB - CBAC COPYRIGHT: CHEM ABS Mice and hamsters uere exposed by inhalation to 50 and/or 500 ppm vinyl chloride monomer (VCM) during 6-18 mo. (75-01-4 Vinyl chloride) Blood samples uere taken at regular intervals during the exposure for anal, of plasma enzymes indicative of liver damage or early malignancy. Some animals were sacrificed for histopathol. examns. after 6 mo and the rest were examd. when dead or moribund. Aik. phosphatase and total lactate dehydrogenase (L0H) activities were elevated in VCM exposed mice. There was also a shift towards cathodic isoenzymes of LDH. The transaminases were not significantly elevated. No changes in plasma enzymes were found in exposed hamsters. Pathol, examn, of VCM-exposed mice showed the presence of hemangiosarcomas in fat tissue, histol. benign alveologenic lung adenomas as well as a few benign and malignant tumors at various sites. Only 1 liver hemangiosarcoma was noted. No liver fibrosis was seen. All mice exposed to 50 ppm VCM for 76 mo developed tumors. Tumor incidence was high also in the hamsters. Enzyme changes occurred late in the study, subsequent to tumor appearance. The value of enzyme changes as a diagnostic criterion on tissue injury or early malignancy caused by VCM was discussed. 33 AU - INFANTE PF TI - MUTAGENIC AND CARCINOGENIC RISKS ASSOCIATED WITH HALOGENATEO OLEFINS SI - HEEP/79/06563 SO - ENVIRON HEALTH PERSFECT; (21). 1977 (RECD 1978) 251-254 AB - HEEP COPYRIGHT: BIOL ABS. MOUSE RAT HUMAN SALMONELLA-TYPHIMURIUM DROSOPHILA VINYL CHLORIDE VINYLIDENE CHLORIDE TRI CHL0R0 ETHYLENE CARCINOGENS OCCUPATIONAL EXPOSURE CHROMOSOMAL ABERRATIONS LUNG SKIN CANCERS 34 AU - LEE C-C ; BHANDARI JC WINSTON JM ', HOUSE WB ; PETERS PJ AU - DIXON RL ; WOODS JS TI - INHALATION TOXICITY OF VINYL CHLORIDE AND VINYLIDENE CHLORIDE SI - HEEP/79/06537 SO - ENVIRON HEALTH PERSPECTJ (21). 1977 (RECO 1978) 25-32 AB - HEEP COPYRIGHT: BIOL ABS. HOUSE RAT MAMMARY GLAND LIVER LUNG KIDNEY DISEASES CARCINOMAS 00003193 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 16 35 AU - MALTONI C TI - RECENT FINDINGS ON THE CARCINOGENICITY OF CHLORINATED OLEFINS SI - HEEP/79/06536 50 - ENVIRON HEALTH PERSPECT; (21). 1977 (RECO 1978) 1-5 AB - HEEP COPYRIGHT: BIOL ABS. RAT MOUSE HAMSTER VINYL CHLORIDE VINYLIDENE CHLORIDE STYRENE ACRYLO NITRILE 01 CHLQRO ETHANE CHLORO FLUORO CARBONS TRI CHLORO ETHYLENE CARBON TETRA CHLORIDE VINYLIDENE FLUORIDE CARCINOGENS SKIN MAMMARY LEUKEMIA FORE STOMACH TUMORS LYMPHOMA 36 AU - WINSTON JM ; LEE CC *, BHANDARI JC J DIXON RL 1 WOODS JS TI - A STUDY OF THE CARCINOGENICITY OF INHALED VINYL CHLORIDE AND VINYLIDENE CHLORIDE IN RATS AND MICE 51 - HEEP/78/0766B 50 - BURFORD, R. G. INTERNATIONAL CONGRESS ON TOXICOLOGY. ABSTRACTS. TORONTO, ONTARIO, CANADA. 52P. INTERNATIONAL CONGRESS ON TOXICOLOGY: TORONTO, ONTARIO, CANADA.; 1977 32 AB - HEEP COPYRIGHT: BIOL ABS. ABSTRACT CARCINOGENS SKIN LUNG BONE LIVER MAMMARY TUMORS BRONCHIOLAR ADENOMA LIVER HEM ANGIO SARCOMA MALIGNANT LYMPHOMA 37 AU - ARYANPUR J AD - Public Health Occup. Med. Serv., Natl. Iranian Oil Co., P.O. Box 1863, Tehran, Iran. TI - Vinyl chloride: Its impact on occupational medicine practice in Iran. 51 - HEEP/78/06299 50 - J OCCUP MED! 19 (10). 1977 689-692 AB - HEEP COPYRIGHT: BIOL ABS. Awareness that VCM (vinyl chloride medicine) has been demonstrated to be a carcinogen producing a rare tumor, angiosarcoma, has led the company to tighten its medical monitoring and industrial hygiene controls. A temporary TLV (threshold limiting value) was established for VCM at 25 ppm consistent with the operating procedures of the company and local geographical conditions. The potential harm from industrial chemicals has stimulated the government and the company to support further control of inplant and outplant environmental hazards from industrial operations. 38 AU - CHIAZZE L JR ; NICHOLS WE ; WONG O AD - Div, Biostatist. Epidemiol., Dep. Community Med. Int. Health, Georgetown Univ. Sch, Med., Washington, D.C, 20007, USA. TI - Mortality among employees of PVC fabricators. 51 - HEEP/78/03515 SO - J OCCUP MED! 19 (9). 1977 623-628 AB - HEEP COPYRIGHT: BIOL ABS. A cross-sectional mortality study of 6391 deaths occurring among current and former employees of 17 PVC (polyvinyl chloride) fabricators during 1966-1973 is presented. The objectives were to identify any angiosarcoma deaths among the employees of these fabricators and to examine distribution of deaths by cause. No angiosarcoma deaths were found among the study group. 5ex-race-cause-speciflc R&S 102669 03 9 cr> 0 I9 Z V 11 00003194 VINYL CHLORIDE. POLYVINYL CHLORIDE / CANCER-RELATED PAGE 17 Proportionate Mortality Ratios (PMR) were computed, using the corresponding USA mortality as the standard. Among white employees, there appeared to be an excess in total cancer mortality, particularly that of the digestive system. Observed deaths apparently exceeded those expected in cancers of the breast and urinary organs among white females. Deficit mortality was observed in cirrhosis of liver among male and female white employees. 39 AU - FOX AJ ; COLLIER PF AD - Off. Pop. Censuses Surv.. St. Catherines House. 10 Kingsway, London WCEB 6JP, Engl., UK. TI - Mortality experience of workers exposed to vinyl chloride monomer in the manufacture of polyvinyl chloride in Great Britain. SI - HEEP/78/01417 SO - BR J IND MED; 34 (1). 1977 1-10 AB - HEEP COPYRIGHT; BIOL ABS. Identification particulars were obtained for over 7000 men who were at some time between 1940-1974 exposed to vinyl chloride monomer in the manufacture of polyvinyl chloride. Approximately 99/ of these men were traced and their mortality experience studied. The overall standardized mortality ratio. 75.4. shows a significant reduction compared with the national rates. Four cases of liver cancer were found; 2 were confirmed by a panel of liver pathologists as angiosarcoma and Z as not angiosarcoma. There is no evidence to support the hypothesis that cancers other than those of the liver are associated with exposure to vinyl chlodrie monomer. The Z cases of angiosarcoma were found in men who were exposed to high concentrations of the monomer although the End man died only 6 yr after 1st exposure. The industry in Great Britain has expanded considerably since the End World War with over 50/ of men having entered within the last decade. 40 AU - NICHOLSON WJ TI - CANCER FOLLOWING OCCUPATIONAL EXPOSURE TO ASBESTOS AND VINYL CHLORIDE SI - HEEP/77/12051 50 - CANCER (PHILA); 39 (SUPPL 4). 1977 1792-1801 AB - HEEP COPYRIGHT: BIOL ABS. HUMAN CARCINOGENS LUNG CANCER 41 AU - Ikeda M AD - Tohoku Univ, Sci. Med., Sendai. Japan TI - Tumoriqenicity of chlorinated ethylenes 51 - CA/087/162E67R SO - Igaku Ho Ayumi ; VOL 10E, ISS 6/7, 1977,453-9 LA - JPN AB - CBAC COPYRIGHT: CHEM ABS A review with 17 refs, of the induction of liver angiosarcoma, hepatocellular carcinoma, nephroblastoma, pulmonary tumor, kidney adenocarcinoma, and mammary carcinoma by vinyl chloride, vinylidene chloride, trichloro- and tetrachloroethylene in rats and mice, including correlation of the effects to dose, age, and sex. (75-01-4 Vinyl chlor1de)(75-35-4 vinylidene chlorideM79-01-6 1 00003X95 VINYL CHLORIDE. POLYVINYL CHLORIDE / CANCER-RELATED PAGE 18 R&S 102671 92 AU AD TI SI SO LA AB 93 AU TI SI SO AB 99 AU AD TI SI SO AB Trichloroethylene)(127-18-9 Tetrachloroethylene) Radike MJ ; Stemmer KL > Brown PG ; Larson E i Bingham E Inst. Environ. Health. Univ. Cincinnati. Cincinnati. Ohio Effect of ethanol and vinyl chloride on the induction of liver tumors: preml Unary report CA/089/018137X Environ. Health Perspect.J VOL 21.. 1977,153-5 ENG CBAC COPYRIGHT: CHEM ABS In rats exposed to 600 ppm vinyl chloride (I) and I plus 57. EtOH that were autopsied, the latent period for angiosarcoma of the liver to appear was 53 wk in rats exposed only to I and 38 wk in rats exposed to I and 57. EtOH, (75-01-9 Vinyl chlorideX69-17-5 Ethanol) Thus, there is a synergism between ingested EtOH and inhaled vinyl chloride in the induction of tumors. BARTSCH H I MALAVEILLE C ; MONTESANO R THE PREDICTIVE VALUE OF TISSUE MEDIATED MUTAGENICITY ASSAYS TO ASSESS THE CARCINOGENIC RISK OF CHEMICALS HEEP/77/08776 MONTESANO, R., H. BARTSCH AND L. TOMATIS (ED.). IARC (INTERNATIONAL AGENCY FOR RESEARCH ON CANCER) SCIENTIFIC PUBLICATIONS, NO. 12. SCREENING TESTS IN CHEMICAL CARCINOGENESIS. PROCEEDINGS OF A WORKSHOP BRUSSELS, BELGIUM, JUNE 9-12, 1975. XX+666P. ILLUS. INTERNATIONAL AGENCY FOR RESEARCH ON CANCER: LYON, FRANCE.) 1976 967-986 HEEP COPYRIGHT: BIOL ABS. HUMAN MOUSE RAT SALMONELLA-TYPHIMURIUM NITROSAMINES VINYL CHLORIDE VINYLIDENE CHLORIDE 2 CHLORO BUTADIENE CARCINOGENS LUNG LIVER KIDNEY TISSUE GOKEL JM ! LIEBEZEIT E ; EDER M Pathol. Inst., Univ., Thalkirchner Str, 36, D-8000 Muenehen 2, W. Ger. Hemangiosarcoma and hepatocellular carcinoma of the liver following vinyl chloride exposure: A report of two cases. HEEP/77/07005 VIRCHOWS ARCH A PATHOL ANAT HISTOU 372 (3). 1976 (RECD 1977) 195-203 HEEP COPYRIGHT: BIOL ABS. A report is given of the clinical and autopsy findings of 2 men who died from malignant liver neoplasms following occupational exposure to vinyl chloride. The 1st patient was a 99 yr old man with a hemangiosarcoma of the liver. The 2nd patient was a 67 yr old man with a hepatocellular carcinoma. Hepatocellular carcinoma due to '<myl chloride was not yet observed in man. Its occurrence was suggested from the results of animal experiments. The connection of hepatocellular carcinoma with exposure to vinyl chloride is discussed. 00003X96 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 19 AS AU - PAGE M ! THERIAULT L ; DELORME F AD - Hotel-Dieu Que., XI Cote Palais, que. G1R 2J6, Can. TI - Elevated CEA levels in polyvinyl chloride workers. SI - HEEP/77/06758 SO - BIOMED EXPRESS (PARIS); 25 (8). 1976 279 AB - HEEP COPYRIGHT: BIOL ABS. Plasma CEA (carcinoembryonic antigen) titer was measured in 200 polyvinyl chloride workers. A positive test was obtained in A8.3X of this high risk population as compared to 9.2X for a normal healthy population. CEA monitoring may be helpful in detecting early liver angiosarcoma. 96 AU - INFANTE PF ; WAGONER JK ; WAXWEILER RJ TI - CARCINOGENIC MUTAGENIC AND TERATOGENIC RISKS ASSOCIATED WITH VINYL CHLORIDE SI - HEEP/77/06571 SO - MUTAT RES; AX (1). 1976 131-1A2 AB - HEEP COPYRIGHT: BIOL ABS. HUMAN ANIMAL LIVER ANGIO SARCOMA BRAIN CENTRAL NERVOUS SYSTEM RESPIRATORY LYMPHATIC HEMATOPOIETIC SYSTEM TUMORS OCCUPATIONAL EXPOSURE A 7 AU - SHABAD LM *, GENIN VA AO - Inst. Clin. Exp. Oncol., Acad. Med. Sc). USSR, Moscow, USSR. TI - A new type of occupational malignant neoplasms induced by vinyl chloride: Review of literature. SI - HEEP/77/05692 SO - GIG TR PROF ZABOLJ (7). 1976 Al-AA AB - HEEP COPYRIGHT: BIOL ABS. A review is qiven of malignant neoplasms in humans and laboratory animals associated with exposure to vinyl chloride or polyvinylchloride resins. Angiosarcoma and various functional impairments of the liver plus malignancies of the lymphatic and hematopoietic tissue, glioblastoma and tumors of the pancreas and skin were reported in workers or nearby residents exposed to atmospheric pollution from polyvinylchloride production. Laboratory animals developed adenoma, adenocarcinoma of the lungs and mammary glands, liver angiocarcinoma and other malignancies. Data are given on production of the carcinogen m western countries and Japan, and measures of prophylaxis, including establishment of maximum permissable concentrations, taken since the 197A designation of vinyl chloride as a carcinogen. No cases of occupational cancer induced by vinyl chloride were registered in the USSR. 98 AU - FIECHTNER JJ ; REYES C N JR AD - Marshfield Clin., 1000 N. Oak Ave. , Marshfield, Wis. 5AAA9, USA. TI - Angiosarcoma of the liver in a rural population: Four cases diaqnosed in a 29-month period. SI - HEEP/77/03976 SO - JAMA (J AM MED ASSOC); 236 (15). 1976 1709-1706 AB - HEEP COPYRIGHT: BIOL ABS. Angiosarcoma of the liver was recently publicized because of its association with polyvinyl chloride (PVC) polymerization workers. Four cases of this rare tumor were observed within a 29 mo. period. There were no R&S 102672 00003197 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 0 factories that manufacture PVC products in the immediate area, nor were any of the victims ever involved in such manufacturing work. Other factors may be related to this cluster of the disease. 49 All - ZAEVA GN AD - Inst. Ind. Hyg. Occup. Dis., Acad. Med. Sci. USSR, Moscow, USSR. TI - Carcinoqenic properties of vinyl chloride1 Literature review. SI - HEEP/77/02385 SO - GIG TR PROF ZABOL; (4). 1976 46-48 AB - HEEP COPYRIGHT: BIOL ABS. Literature data on the carcinogenic properties of vinyl chloride (VC) are presented. Statistics revealed 45 cases of liver angiosarcoma in persons occupationally exposed to VC in 10 countries (USA, Canada, CHSSR (Czechoslovakia), France, Great Britain, Italy, Norway, Rumania, Sweden and FRG (West Germany)). Most reports of these cases were published during the past 7 yr. The mean latent period of tumor development was about E0 yr. The blastomogenic action of VC was also confirmed in experiments in animals with concentrations in a range of 75,000-130 mg/m3. The VC concentration of 130 mg/m3 produced minimal blastomogenic effect. In the USSR the maximum permissible concentration of VC in the production sector is 30 mg/m3. In the USA the hygienic standard is at present reduced from 1300 to 2.6 mg/m3. The results of statistical and experimental investigations justified referring VC to the category of occupational carcinogens. 50 AU - BOLT HM ; KAPPUS H ; BUCHTER A ; BOLT W AD - Inst. Toxikol. , Univ. Wilhelmstr. 56, D-7400 Tuebingen, W. Ger. TI - Disposition of (1,2-140 vinyl chloride in the rat. SI - HEEP/77/01202 SO - ARCH TOXICOL! 35 (3). 1976 153-162 AB - HEEP COPYRIGHT: BIOL ABS. Rats were exposed to the carcinogen (1,2~14C) vinyl chloride in a closed system at initial concentrations below 100 ppm. When the system was occupied by 3 rats, a half-life of vinyl chloride in the system's atmosphere of 1.13 t 0.12 h was observed. The volume of the system was 10.3 1. Calculation of the clearance of vinyl chloride from the system revealed that about 40X of inspired vinyl chloride is absorbed by lung. Changes in respiration did not influence uptake of vinyl chloride. Uptake of vinyl chloride by the rats was completely blocked by acute pretreatment with potent inhibitors of cytochrome P-450 dependent microsomal drug metabolism (i.e., 35 mg/kg 3-bromopheny1-4(5)~imidazole or 50 mg/kg 6-nitro-1,2,3-benzothiadiazole in 0.6 ml/kg OMSO (dimethylsulfoxide)), A weaker inhibition was observed after SKF 525 A (2-dimethyIaminoethy1-2,2-diphenyl valerate) or 5,6-dimethyi-l,2,3-benzothiadiazole (50 mg/kg in 0.6 ml/kg DMS0). Metyrapone did not cause inhibition. Uptake of vinyl chloride was increased by pretreatment with DDT and, to a lesser extent, clotrimazol. No significant stimulation of uptake was observed after pretreatment with phenobarbital, 3-methylcholanthrene , rifampicin or chronic ethanol treatment. Immediately after exposure, highest radioactivity levels were observed in liver and 00003198 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 21 kidney. The radioactive metabolites of 14C-vinyl chloride were rapidly excreted, largely by the kidneys. Excretion of radioactivity in the urine was 69.4 t 2.6/C within 24 h. 51 All - WITHEY JR TI - Pharmacodynamics and uptake of vinyl chloride monomer administered by various routes to rats. SI - HEEP/76/08961 50 - J TOXICOL ENVIRON HEALTH; 1 (31. 1976 381-394 AB - HEEP COPYRIGHT: BIOL ABS. Finding at least 2-3 ppm and occasionally as much as 10-20 ppm of vinyl chloride monomer in a wide range of foodstuffs prompted concern for a possible human health hazard. The recognition of vinyl chloride as a carcinogen to human in April, 1974, following the discovery of angiosarcoma as the cause of death in at least 25 workers who were engaged in the manufacture of polyvinyl chloride, enhanced this concern with respect to the presence of vinyl chloride monomer in foods. To assess the hazard presented by the oral ingestion of vinyl chloride monomer, rats that were surgically prepared with an indwelling jugular cannula were dosed by intragastric intubation with aqueous solutions containing up to 2.0 mg/ml vinyl chloride. Time-concentration curves were obtained from sequential samples of blood. The uptake of vinyl chloride by this route was extremely rapid. Peak concentrations were achieved less than 10 min after administration of the dose. Elimination from the blood compartment appeared to be biexponential. Studies with the same animal model in a single restraint cage that allowed a head only exposure to concentrations of vinyl chloride up to 7000 ppm in the gas phase showed a similar rapid uptake followed by a plateau blood concentration during several hours of exposure. On removal from the vinyl chloride atmosphere, blood levels fell rapidly to barely detectable concentrations after 2 h. The precise kinetic coefficients that describe the distribution and elimination rates of vinyl chloride from the blood compartment were also determined from the blood concentration data after the administration of an i.v. dose of aqueous or vegetable oil solution. 52 AU - WHELAN J G JR ', CREECH JL J TAMBURRO CH TI - Angiographic and radionuclide characterist1cs of hepatic angiosarcoma found in vinyl chloride workers. 51 - HEEP/76/08407 SO - RADIOLOGY; 118 (3). 1976 549-557 AB - HEEP COPYRIGHT: BIOL ABS. Hepatic angiosarcoma, recently discovered in a large series of vinyl chloride workers, demonstrates characteristic angiographic and radionuclide changes. Tumors exhibiting central hypovascularity with puddling are usually surrounded by a peripheral stain. A negative peripheral defect is demonstrated on the hepatic scan. Healing hepatic infarction secondary to wedged hepatic venography creates a false-positive lesion on angiography similar to angiosarcoma. Splenomegaly and systemic venous hypertension develop in a number of these patients. R&S 102674 R&S 102675 00003199 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 22 53 AU - Shabad LM I Genin VA AO - Inst. EKsp. Klin. Onkol., Moscow, USSR TI - New type of occupational malignant neoplasms induced by vinyl chloride SI - CA/087/010519M SO - Gig. Tr. Prof. Zabol.I ISS 7, 1976,41-4 LA - RUS AB - CBAC COPYRIGHT: CHEM ABS Evidence is found in the literature on vinyl chloride monomer (VVM)-induced liver angiosarcoma, preceded by a complex of specific morphol. changes such as thrombocytopenia, splenomegalia, and hepatomegalia in addn. to portal fibrosis, fibrosis of liver capsule, and signs of acroosteolysls . (75-01-4 Vinyl chloride) Malignant neoplasms including liver hemangiosarcomia, tumors of lymphatic and hematopoietic tissues. Pancreas and bone cancer was the cause of death of 9 out of 24 deceased VCtl ex-operators. Exptl. animals exposed to VCM developed subcutaneous and liver angiosarcomas, lymphonia, melanoma skin trichoepithelioma, and transplacentary biastomogenesis . An awareness of the carcinogenic properties of VCM stimulated the revision of the MAC which created the necessity for the soln. of prophylactic and sanitary-technol. problems . 54 AU - Orusev T I Popovski P i Bauer S ; Nikolova K AD - Yugoslavia TI - Occupational risk in the production of poly(vinyl chloride) SI - CA/086/194336H SO - God. Zb. Med. Fak. Skopje! VOL 22,, 1976,33-8 LA - Macedonian AB - CBAC COPYRIGHT: CHEM ABS Vinyl chloride concns. >75 ppm were measured m the air of a PVC plant. (75-01-4 Vinyl chloride)(9002-86-2 PVC) Examn. of 103 workers revealed 2 cases of enlarged liver, 2 cases of Raynaud syndrome, 2 cases of acroosteolys i s, 1 case of lung cancer, and increased incidence of circulatory insufficiencies. 55 AU - Colvin M i Brundrett RB ; Cowens W i Jardine I ! Ludlum 0B AD - Sch. Med., Johns Hopkins Univ., Baltimore, Md. TI - A chemical basis for the antitumor activity of chloroethylnitrosoureas SI - CA/085/072048Z SO - Biochem. Pharmacol.! VOL 25, ISS 6, 1976,695-9 LA - ENG AB - CBAC COPYRIGHT: CHEM ABS The aq. decompn. of haloethyInitrosoureas , e.g, 1,3-bis-chloroethyl-l-nitrosurea (I), was studied and related to their antitumor activity. (154-93-8 1,3-Bis-chloroethyl-l-nitrosourea ) E.g., I, which has antitumor activity, decomposed to haloethanol, vinyl halide, dihaloethane, and MeCHO, whereas 1-chloroethy1-3,3-dimethyl-l-ni trosourea, which was not toxic to murine L1210 leukemia cells, generated MeCHO but not the other volatile compds. (75-07-0 Acetaldehyde 1(59960-30-4 00003200 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 23 R&S 102676 l-Chloroethyl-3>3-dimethyl-l-nitrosourea) In contrast to the disubstituted nitrosoureas, 1-chloroethyl-l-nitrosourea, which has high antitumor activity, did not generate an org. isocyanate on aq. decompn. (2365-30-2 1-Chloroethyl-l-nitrosourea ) These data support the hypothesis that the antitumor activity of chloroethylnitrosoureas is due to ethyl carbonium ion (or diazonium precursor) generation. 56 AU - Thomas LB I Popper H ; Berk PD i Salikoff I ; Falk H TI - Vinyl chloride induced liver disease SI - IPA/75/03331 SO - N. Engl. J. Mad.; VOL 292 ISS Jan 2 1975, P17-21, (REF 32) AB - IPA COPYRIGHT: ASHP Histologic examination of liver tissue (8 autopsy and 18 biopsy specimens) and 4 spleens from 20 workers with vinyl chloride polymerization showed hepatic angiosarcomas in 15. In addition, a peculiar pattern of progressive portal tract, inconspicuous intralobular and conspicuous capsular fibrosis was observed in the 5 workers without angiosarcoma, in all the 7 patients with angiosarcoma from whom tumor free portions of the liver were available, and in 2 tumor free biopsies from patients subsequently found to have angiosarcoma. The fibrosis was accompanied by splenomegaly. Hypertrophy and hyperplasia of both hepatocytes and hepatic and splenic mesenchymal cells were also seen. The histologic similarity to chronic inorganic arsenical poisoning, in which angiosarcomas also occur, and to idiopathic portal hypertension (Banti's syndrome) suggests that the latter syndrome at times results from unknown toxic, possibly environmental, chemicals. APPENDED: Vinyl chloride toxicity, environmental Toxicity, environmental vinyl chloride Polymers vinyl chloride 57 AU - SE LINGER M KOFF RS TI - Thorotrast and the liver: A reminder. SI - HEEP/76/10098 SO - GASTROENTEROLOGY; 68 <(4 PART I) ). 1975 799-803 AB - HEEP COPYRIGHT: BIOL ABS. New insights into carcinogenesis might by gained by further study of Thorotrast-induced human neoplasia. The role of immune mechanisms in the induction of these tumors is uncertain. Thorotrast neoplasms may be RES tumors of multicentric origin. Although exposure to ionizing radiation would appear to be the primary inciting mechanism of Thorotrast carcinogenesis in the liver, no association between liver cell carcinoma or cholangiocarcinoma and atomic bomb exposure was identified in an autopsy series from Hiroshima and Nagasaki (Japan). The possibility of a foreign body or chemical reaction, resembling As-induced malignancy, was also suggested. Although knowledge of vinyl chloride-induced hepatotoxieity is currently limited, the clinical features of vinyl chloride liver disease resemble those associated with Thorotrast. Similarities in latent period and in the development of fibrosis, cirrhosis and angiosarcoma are striking. Whether vinyl chloride-induced carcinogenesis and hepatic injury share features other than clinical expression with Thorotrast remains to be determined. 00003201 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 24 R&s 102677 Regardless of the mechanises of Thorotrast sequelae, it Is apparent that carriers represent a population at risk for the development of liver disease and deserves the attention of hepatologis ts . 58 AU - BARTSCH H ; MONTESANO R TI - Mutagenic and carcinogenic effects of vinyl chloride. SI - HEEP/76/09363 SO - MUTAT RES; 32 (2). 1975 (RECD 1976) 93-114 AB - HEEP COPYRIGHT: BIOL ABS. The carcinogenicity of VCM (vinylchloride monomer) in animals and man and its mutagenic action after metabolic conversion by microsomal enzymes from humans and rodents into electrophilic derivatives further strengthen the establishment of a formal relationship between carcinogenesis and mutagenesis. The screening of a large number of chemicals which are produced on a massive scale and for which a human exposure exists by such mutagenicity assays, in which mammalian and human metabolism are taken into account, would be of great value in the detection of biological hazards. An example of such a chemical is one that is structurally related to VCM 1,1-dichloroethylene (vinylidene chloride), and which is used almost exclusively as a copolymer of VCM in the production of plastic materials. This compound induces point mutation in Salmonella typhimurium strains when assayed in the presence of rat or mouse liver fraction in vitro. Its mutagenic activity is higher than that of VCM. Vinylidene chloride is toxic at high concentrations, and it is carcinogenic in rats. Another chemically related substance, 2-chlorobutadiene (chloroprene ), used in the manufacture of synthetic rubber since 1930, was recently suggested as being responsible for an increased incidence of skin and lung cancer in exposed workers, and its activity to induce point mutation in S. typhimurium was demonstrated. The available data indicate that polymerization workers are at a very high risk of angiosarcoma of the liver. Among some 5600 workers currently employed at 36 PVC (polyvinyl chloride) polymerization plants in the U.S.A., 15 cases of angiosarcoma of the liver were reported in 4 of these plants. Nine cases were found m a single plant employing less than 300 workers, and 1 case, a polymerization worker, was exposed to VCM for only 4 yr. Populations at lower levels of exposure are also at risk, as shown by the observation of angiosarcoma of the liver in workers employed in PVC-fabrlcating plants. The occurrence of few cases of angiosarcoma of the liver among nonoccupationally exposed people and a clustering of cases in a heavily industrialized area could be connected with factory discharge of VCM in the air. Another source of human exposure to VCM is food and beverages packed in PVC containers, since VCM migrates into these commodities. The daily human oral intake was estimated to be less than 100 mug VCM. Since scientific knowledge of chemical carcinogenesis cannot allow the establishment of a safe exposure level for any carcinoqen, every effort should be made to prevent exposure and minimize the risk. 00003202 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 25 59 AU - ZIMMERMANN H ; ECK H TI - Pathological anatomy of vinyl chloride disease. SI - HEEP/76/09520 50 - VIRCHOWS ARCH A PATHOL ANAT HISTOL; 368 (1). 1975 51-59 AB - HEEP COPYRIGHT! BIOL ABS. A lethal case of angiosarcoma of the liver is reported, A 38 yr old chemical laboratory assistant was exposed in vinyl chloride (VC) for about 3 1/2 yr. The sarcoma metastasized to many other organs. This case is the 5th reported in the German Federal Republic. In 9 of the cases the patient died. VC concentration at the work place was not measured. Thrombocytopenia observed in about 80/ of the VC cases was not seen. There will possibly be further VC-caused tumors in the population. There might be other extrahepatic VC-caused tumors in man, which could be determined by animal experimental investigations. 60 AU - CHABALKO JJ ; FRAUMENI J F JR TI - Blood-vessel neoplasms in children: Epidemiologic aspects. 51 - HEEP/76/0292B 50 - MED PEDIATR ONCOL; 1(2). 1975 135-192 AB - HEEP COPYRIGHT: BIOL ABS. In a search for etiologie leads to blood vessel neoplasms, 111 death certificates of U.S. children who died from 1960-1968 of angiosarcoma, hemangioendothelioma, and hemangiopericytoma and 127 medical records of similar cases for 12 institutes were examined. The available data provided no leads to environmental agents (vinyl chloride, Thorotrast, As) that can produce vascular liver tumors in adults, but 1 infant, who died from a hepatic tumor, lived within a mile of an industrical source of polyvinyl chloride. About half of the children with hepatic hemangioendotheliomas had associated skin hemangiomas, which may aid in the differential diagnosis of liver tumors in infancy. Hepatic hemangioendotheliomas also predominated in girls, a possible clue to the origin of the tumor. A familial influence was suggested by 1 sibling aggregation of cutaneous hemangioendotheliomas. 61 AU - REIN FR ; HUTH F TI - Six spontaneous primary malignant vascular tumors of the liver in 30,000 antopsies. 51 - HEEP/76/00073 SO - INT ARCH ARBEITSMEO; 39 (9). 1975 237-296 AB - HEEP COPYRIGHT: BIOL ABS. The records of 30,079 autopsies done from 1959-1979 were examined for primary malignant vascular tumors of the liver. Six cases were found (3 males, 3 females, aged between 36 and 76) and histologically reinvestigated. In 9 cases an angiosarcoma was diagnosed, in 1 case a hemangioendothelioma and in another a malignant hemangiopericytoma. Examination of family and case histories, as well as questioning of factory insurance companies and neighbors, led to the conclusion that there was no contact of the subjects with factories producing vinyl chloride. A rate of spontaneous primary malignant vascular tumors of the liver of 0.2/ must be R&S 102678 R&S 102679 00003203 VINYL CHLORIDE. POLYVINYL CHLORIDE / CANCER-RELATED PAGE 26 considered with regard to hepatic tumors following contact with industrial toxic substances. 62 AU - BARTSCH H ; MALAVEILLE C *> MONTESANO R TI - Human, rat and mouse livei--mediated mutagenicity of vinyl chloride in S. typhimurium strains. SI - HEEP/75/09322 50 - INT J CANCER', 15 (3). 1975 429-437 AB - HEEP COPYRIGHT: BIOL ABS, Exposure of S. typhimurium strains TA 1530. TA 1535 and G-46 to the carcinogen vinyl chloride increased the number of His+ revertants/plate 16. 12 or 5 times over the spontaneous mutation rate. After 6 h of exposure to vinyl chloride, the mutagenic response for TA 1530 strain was enhanced 7-. 4- or 5-fold when fortified postmitochondrial liver fractions from humans, rots or mice were added. The enzyme-mediated vinyl chloride mutagenicity was dependent on an NADPH generating system and the enzyme activity was localized in a liver microsomal fraction; 9.000 x g liver supernatant wo3 3 times more active than microsomes. while liver cytosol or alcohol dehydrogenase did not affect the mutagenicity. Phenobarbitone pretreatment of rats and mice increased the mutagenic response by 15-40/t as compared to untreated controls. The relative mutagenic activities of VCM (vinyl chloride monomer), taking the value from mouse liver as 100. for TA 1530 strain mediated by 9.000 x g tissue fractions were: rat liver 80; mouse and rat kidney. 20 and 16; mouse and rat lung, less than 7; human liver (from 4 biopsy specimens). 170. 64, 70 and 46. Chloroacetaldehyde and chloroacetic acid, a urinary metabolite of VCM, showed toxic effects, while chloroethanol was weakly mutagenic for the TA 1530 strain, 63 AU - Flesch JP ; Rostand RA AD - Natl. Inst. Occup. Saf. Health, Cincinnati, Ohio TI - Health hazard evaluation/toxicity determination report H.H.E. 74-94-253. Armstrong Cork Company, Jackson, Mississippi 51 - CA/085/181695D 50 - U. S. NTIS, PB Rep.; ISS PB-249433,, 1975,16 pp. LA - ENG AB - CBAC COPYRIGHT: CHEM ABS A health hazard existed from exposure to airborne Chrysotile and vinyl chloride in the manuf. of vinyl asbestos floor tiles no findings sugqestive of lung cancer were obsd. (12001-29-5 Chrysotile )(75-01-4 Vinyl chloride) 64 AU - Maitoni C ; Lefemine G AD - Italy TI - Use of experimental tests in the prediction of environmental oncogenic risk. Vinyl chloride 51 - CA/083/158884Q SO - Atti Accad. Naz. Li neei, Cl. Sci. Fis. , Mat. Nat., Rend.; VOL 56, ISS 3, 1975,412-22 LA - ITA AB - CBAC COPYRIGHT: CHEM ABS Preliminary results are reported for a comprehensive study of the carcinogenicity of vinyl chloride with 00003204 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 27 R&S 102680 65 AU AO TI SI SO LA AB 66 AU TI SI SO AB respect to species and age of the test animals, route of administration, dose, duration of exposure, etc. (75-01-4 Vinyl chloride) Vinyl chloride caused carcinomas of Zymbal's glands, nephroblastomas, and hepatic and extrahepatic angiosarcomas in rats and lung tumors, mammary carcinomas, and hepatic angiosarcomas in mice. A dose-response relation uas found. These exptl. carcinogenicity bioassays with vinyl chloride are considered highly predictive of effects of industrial exposure of workers. Similar testing of other potentially hazardous industrial substances is advocated. Maltoni C ; Lefemine G 1st. Oncol., Bologna, Italy Carcinogenicity bioassays of vinyl chloride. Current results CA/082/133813G Ann. N. Y. Acad. Sci.J VOL 246.,, 1975,195-218 ENG CBAC COPYRIGHT-- CHEM ABS Vinyl chloride (VC) induced tumors in rats, mice, and hamsters, and the spectrum of induced tumors varied from species to species. (75-01-4 Vinyl chloride) E.g., VC produced lung adenomas, mammary carcinomas, liver angiosarcomas and angiomas and skin epithelial tumors in mice, but produced Zymbal gland carcinomas, liver nephroblastomas and angiosarcomas, skin carcinoma, hepatomas and brain neuroblastomas in rats. The strain factor also affected the neoplastic response as reflected by the results obtained from Sprague-Dauley rats and Wistor rats. Two s.c. angiosarcomas were obsd. in the offspring of breeders exposed to VC during pregnancy for 7 days, indicating a transplacental effect. The observation of a few cases of ossifying angiosarcomas suggested a new orientation in the pathogenetic interpretation of acroosteolysis in workers exposed to VC. Monson RR ; Peters JH Proportional mortality among vinyl chloride workers IPA/75/00509 Lancet; VOL 2 I5S Aug 17 1974, P397-398, (REF 4) IPA COPYRIGHT: ASHP In a proportional-mortality analysis of 161 deceased workers in 2 plants using vinyl chloride, a 50X excess of deaths due to all cancer was seen. Specific sites of cancer with the greatest excess included liver and biliary tract, lung, and brain. The excess in fatal cancer was seen mainly in men who died before age 60. Also, there was a trend in time in the ratio of observed to expected deaths: since 1970 over twice as many cancer deaths os expected have occurred. APPENDED: Toxicity, environmental vinyl chloride Vinyl chloride toxicity, environmental Solvents vinyl chloride 00003205 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 28 67 AU - Lee FI ; Harry OS TI - Angiosarcoma of the liver in a vinyl chloride worker SI - IPA/74/04737 50 - Lancet! VOL 1 ISS Jun 29 1974, P1316-1318, (REF 16) AB - IPA COPYRIGHT: ASHP A 71-year-old man, who had been a process worker in the manufacture of polyvinyl chloride from vinyl chloride monomer for 20 years, died with angiosarcoma of the liver. The evidence appears strong that angiosarcoma of the liver is an occupational tumor and that vinyl chloride is the carcinogen. There is no evidence that the finished polymer carries any risk. APPENDED: Toxicity, environmental polyvinyl chloride Polyvinyl chloride toxicity, environmental Carcinogens vinyl chloride Vinyl chloride carcinogens Toxicity, environmental vinyl chloride 68 AU - EPSTEIN SS AD - Dep. Pharmacol., Case West. Reserve Univ. Sch. Med., Cleveland, Ohio 44106, USA. TI - Environmental determinants of human cancer. 51 - HEEP/77/00069 SO - CANCER RES; 34 (10). 1974 2425-2435 AB - HEEP COPYRIGHT: BIOL AB5. The best documented and most significant data on carcinogenesis due to environmental chemicals are those on tobacco. It was suspected for several decades that heavy tobacco smoking is directly and causally related to chronic lung disease, especially cancer. There are also many studies that demonstrate the contributory role of urban air pollution in lung cancer; and numerous classes of chemical carcinogens were identified in polluted urban air. There is an excess of lung cancer deaths in smokers in polluted urban areas in contrast with those living in rural areas. Similar striking regional variations in the occurrence of a wide range of other organ cancers are now well recognised. The high incidence of cancer of the oral cavity in Asia, representing some 35'/. of all Asiatic cancers, in contrast to IX of all European cancers, is related to the chewing of betel nuts and tobacco leaves. The high incidence of liver cancer in the Bantu and in Guam may be due to dietary contamination with aflatoxin, and to eating cycad plants, containing azoxyglucoside carcinogens, respectively. The high incidence of gastric cancer in Japan, Iceland and Chile was associated with high dietary intake of fish; suggestions were made implicating nitrosamines, formed by reactions between secondary amines in fish and nitrite preservatlves. The high incidence of cancer of the esophagus in Zambians drinking Kachasu spirits, in the Calvados area of France, and in other clearly defined geographic areas may be related to contamination of alcoholic drinks or food with nitrosamines, some of which produce esophageal cancer in experimental animals. Occupational cancers include bladder cancer in the aniline dye and rubber industry, which is induced by such chemicals as 2-naphthylamine, benzidine and 2-aminobiphenyl; 2-nitrobiphenyl induced lung cancer in miners of Colorado, coke oven workers, nitrogen mustard factory R&S 102681 00003206 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 29 workers in Japan, and in USA workers even briefly exposed to bisichloromethyl) ether! skin cancer in cutting and shale oil workers! nasal sinus cancer in wood workers! lung cancer and pleural mesotheliomas in insulation workers and in others, such as construction workers, exposed to asbestos! cancer of the pancreas and lymphomas in organic chemists! and angiosarcoma of the liver in workers involved in polymerization processes for the manufacture of polyvinyl chloride. 69 AU - HOLHBERG B ! MOLINA G TI - The industrial toxicology of vinyl chloride1 A review. SI - HEEP/7S/10337 SO - WORK-ENVIRON-HEALTH! 11 (3). 1974 (RECD 1975) 136-144 AB - HEEP COPYRIGHT: BIOL ABS. Acroosteolysis, Raynaud's phenomenon, scleroderma, liver dysfunction and liver angiosarcoma in workers occupationally exposed to vinyl chloride are discussed and toxic and carcinogenic manifestations noted in laboratory animals exposed to vinyl chloride are summarized. 70 AU - FALK H ! CREECH J L JR ! HEATH C W JR ; JOHNSON MN ! KEY MM TI - Hepatic disease among workers at a vinyl chloride polymerization plant. SI - HEEP/75/02654 SO - JAMA (J AM MED ASSOC); 230 (1). 1974 59-63 AB - HEEP COPYRIGHT: BIOL ABS. Eleven cases of hepatic disease, including 7 cases of hepatic angiosarcoma were identified to date among men employed at 1 vinyl chloride polymerization plant. The earliest diagnosis was made in Apr. 1964. The 2 most recent cases, both angiosarcoma, were diagnosed in Feb. 1974 as a result of systematic medical screening for liver abnormalities among workers at the plant. Ages at diagnosis have ranged from 36 to 58 yr for the 7 patients with angiosarcoma and from 28 to 56 yr to the 4 patients with normalignant disease; durations of employment before diagnosis have ranged from 12 to 28 yr and from 5 to 29 yr. All 11 persons had worked in close and continuous contact with various phases of the vinyl chloride polymerization process. Review of pathologic material suggests the presence in both tumor and nontumor case3 of portal fibrosis and atypical sinusoidal lining cells. A direct casusal relationship between exposure to vinyl chloride monomer and pathologic findings is postulated. 71 AU - HALTOHI C ! LEFEMINE G TI - Carcinogenicity bioassays of vinyl chloride: I. Research plan and early results. SI - HEEP/75/01564 SO - ENVIRON RES! 7 (3). 1974 387-405 AB - HEEP COPYRIGHT: BIOL ABS. These investigations ore concerned with determining the oncogenic potentialities of vinyl chloride (VC) m experimental animals. The effect of this compound is being studied in relation to various experimental factors, such as route of administration, dose level, length of treatment, species, strain and age of the animals. Preliminary results are I 00003207 VINYL CHLORIDE. POLYVINYL CHLORIDE / CANCER-RELATED PAGE 30 R&S 102683 presented. When given by inhalation, VC induces Zymbal gland carcinomas, nephroblastomas and angiosarcomas of the liver and other anatomical sites in rats. In mice, pulmonary adenomas, mammary carcinomas and liver angiosarcomas were noted. A direct relationship was found between dose and length of treatment and neoplastic response. 72 AU - Blyum RA ; Zebenkiene B ; Lutsenko VV ; Liutkiene R AU - Simkeviciene V AD - Vilnius, USSR TI - Some hexamethylenebis(N-nitrosourea) derivatives SI - CA/087/161408A 50 - Tesisy Dokl. - Vses. Konf. Khimioter. Zlokach. Opukholei, 2nd; 1974,80-2 LA - RUS AB - CBAC COPYRIGHT: CHEN ABS Four compds. of the general formula (CH216CN(NO1COMHR]2 (I) were synthesised and tested for antitumor activity in exptl. animals. The most active was I (R = CH2CH20H), which inhibited Walker careinosarcoma by 54.2X and sarcoma 45 by 90.2X. The similar compd. I (R = CH2CH2C1 ) inhibited the tumors by 88.6 and 75.7X, resp. Both compds. had the same toxicity, with an LD100 of 500-600 mg/kg, and both lowered spleen wt. and leukocyte no. Compds. I (R = CH2C0ZH) and I (R = CH2C02- +NH3C6H11 were less toxic, but had no antitumor activity. R = CH2CH20H was also very active against exptl. leukosis. Compds. I (R = CH2CH20H ), I (R = CH2CH2C1), and hexamethylenebis CN1 - (2-chloroethylene JureaJ accumulated primorily in the spleen, while none of the compds. accumulated in the brain. (32903-82-5 HexamethylenebisCN'-(2-chloroethylenelurea) ) 73 AU - Maltoni C ; Lefemine G ; Chieco P ; Carrettl D AD - 1st. Oncol., Bologna, Italy TI - Vinyl chloride carcinogenesis. Current results and perspectives 51 - CA/083/091871N SO - Med. Lav.; VOL 65, ISS 11-12, 1974,421-44 LA - ENS AB - CBAC COPYRIGHT: CHEM ABS Inhalation of vinyl chloride induced tumors in rats in a dose-dependent manner: at 50-500 ppm it caused angiosarcomas aad at 50-250 ppm nephroblastomas. (75-01-4 Vinyl chloride) The induction of the angiosarcomas and nephroblastomas was also dependent on the time of exposure. Subcutaneous angiosarcomas and a Zymbal gland carcinoma occurred in the offspring of rats exposed to vinyl chloride during 7 days of 4 hr daily treatment. Vinyl chloride was carcinogenic also for mice and hamsters. 00003208 VINYL CHLORIDE, POLYVINYL CHLORIDE / CANCER-RELATED PAGE 31 74 AU - VIOLA PL I BIGQTTI A i CAPUTO A TI - Oncogenic response of rat skin, lungs, and bones to vinyl chloride. SI - HEEP/73/00108 SO - CANCER RES; 31 (5). 1971 516-522 AB - HEEP COPYRIGHT: BIOL ABS. Rots (Ar/IRE Ulster strain) exposed for 12 mo. to vapors of vinyl chloride developed tumors of the skin, lungs and bones. The cutaneous tumors, which always appeared in the area in which submaxillary and parotid glands are located, were histologically recognised as epidermoid carcinomas, papillomas, and mucoepidermoid carcinomas. The morphological characteristics of lung tumors, which occurred in a lower percentage, were mainly of the adenocarcinoma type, with the exception of a single epidermoid tumor originating from the epithelial covering cells. In a minor number of rats, a large proliferation of cartilaginous tissue diagnosed as osteochondroma developed in the metacarpal and metatarsal regions of the 4 limbs. *##* END OF OFFLINE PRINT ##### R&S 102684