Document 0qZzOGJk62yVeEG8M5KJrkNam

mc-/^9o 3J CO co CD <0 ->l (0 c P7C31022 itltitifitititifififititifififif,fitititititif,fifififi4ifififif,f,,,titifittf1ftfiftftfififitititttttittftftftflftfifififififititttifitififtf * it * THIS IS AN OFF-LINE BIBLIOGRAPHIC CITATION LIST GENERATED BY it * C* * MEDLARS II # cif it * N.L.H.'S NATIONAL INTERACTIVE RETRIEVAL SERVICE * * c* c* it it if if if it *itif it if it if ****** it if if it it it*# if if if if if if if if if *#*#***#*#*#*#*.##*#*###*#*#*###*## (c VINYL CHLORIDE NUMBER OF CITATIONS PRINTED = 300 JANUARY 27, 1983 THIS SEARCH WAS PERFORMED ON THE CANCERLINE FILE. SORT WAS NOT REQUESTED c PLEASE SEND THIS LISTING TO c STAN KLESNEY PC3 170A MIDLAND, MICHIGAN, 43640 e c c c L ^ ">,', i'v'O- .\'.: " ...-,... ,, 00005579 VINYL CHLORIDE PAGE 1 1 Al) - Clemens MR ; Frank H i Rammer H J Waller HD AO - Medicinische Klinik, Abt. II,Institut fur Toxikologie der Uni vers) Tat 2, Tubingen, W. German',' TI - VIHYLCHLORIDE: A CARCINOGENIC METAEOLITE OF BCNU (MEETING A3STRACT). SI - HERN/33/00917 50 - BluTI 95:233 1932 la - eng AD - Tiie DroducTion of vinyl chloride t-ias first observedduring experiments on the metabolism of BCNU (Carmustlne). Erythrocytes u-sra incubated with BCNU (75 uM) in head space vials. Gases in the head space were analysed by gas chromatography and mass Spectrometry. Vinyl chloride and acetylene were Identified. Vinyl chloride develops from 1.3-bis (2 chioroethyl )-l-nitrosourea in red blood cells bv cleavage of 2 chioroethyl groups of nitrosourea. This reaction is not influenced by superoxide anions since addition of superoxide dismutase (50-500 Units) did not alter the development of >'i ny Ichlor i de. The production of vinyl chloride from BCN'J is important because it is known To be a strong carcinogen, (no Refs) 2 AU Versen P AD - Employment Accident Insurance Fund of the Chemical Industry, Gai sbergstrasse 7, 0 6900 Heidelberg, W, Germany TI - VINYL CHLORIDE DISEASE IN THE FEDERAL REFU3LIC OF GERMANY DEVELOPMENT - COUNTER-MEASURES - PRESENT SITUATION - CONCLUSION (MEETING ABSTRACT) 51 - HERN/S2/19119 SO - Eighth International Conference of Occupational Health in the Chemical Industry, Sept 22-25. 130, Tokyo Permanent Commission and International Association on Occupational Health, pp. S5-06, 1930. LA - ENG AB - Only since 1972 have cases of people being taken ill due to exposure to vinyl chloride (VC) been registered in the Federal Republic of Germany. The number of reported cases reached a peak of 121 in 1979) in 1979 there were only 9 cases. Altogether 319 cases were to be judged. In 102 cases an occupational disease was recognised. Of these, 33 cases were sliqht, 26 moderately severe, 23 severe and 15 died of a hemanqiosarccma of the liver. A survey of The counter-measures introduced is qu'en, eg with regard To reduction of exposure and occuoatIonal medical check-ups. The results are classified. Fibrosis of ike lungs due To polyvinyl chloride (PVC) dust could not be found. IT is still under discussion whether* cases of encephalopathy are to be recognised as a result of VC intoxication. 5o far no satisfactory explanation could be found why the people Taken ill are distributed so unevenly over the individual factories which produce PVC. Yet even if certain Things remain unexplained, it seems justified nowadays in respect of vinyl chloride disease to say "Recoqnlslng a risk is a major steo towards eliminating it", (no Pe f s ) oooossso VINYL CHLORIDE PAGE Z 3 AU - Thiess AM ', Link R AD - BASF Aktiengggeilschaft> Occuoational Medicine and Health Protection, 6700 Ludwigshpfen, Rhine, Federal Republic of Germany TI - EPIDEMIOLOGICAL MORTALITY STUDIES IH THE CHEMICAL IHDUSTRY BASF AKTIENGESELLSCHAFT, LUD'dIGSHAFEM, FEDERAL REPUBLIC OF GERMAMY (MEETING A3STRACT) SI - HERN/S2/15053 50 - Eighth International Conference of Occupational Health in the Chemical Industry, Sept 22-25, 19S0, Tokyo Permanent Commission and International Association on Occupational Health, pp. S4-Q9, 1950. LA - EHS AB - Epidemiological mortality studies have been undertaken in the BASF since 1974, The program covers prospective mortality studies on skilled chemical workers, emanating from exposure to health-impairing substances. A significant increase in the number of observed cases of cancer deaths in comparison to the expected cancer rate was only found in the tr i chlcr'phenol-dl oxi n cohort which was exposed to dioxin after an accident In 1953. A clear but not significant increase of observed against expected cancer deaths was found in the truck driver cohort. Onl1' a slight increase in the number of cancer deaths could be observed in the cohorts with exposure to auramlne, crTho-phThalcdlnitrile, vinyl chloride and vinylidene chloride. Ho increased rates of cancer deaths were found in the cohorts exposed to cadmium, chloroqulnone , di-2-ethylhexylphthalaie, ethvlbencene residue and styrene. Due to the high rate of mixed exposures it is difficult to evaluate the results in the case of acrylcmtr i le which is suspected to be a carcinogenic risk to man. (no Refs) 4 AU - Kakayama E t Hishicawa T ; S'nibata T t Nagano K ; Oo'oayashi H AD - Occupational Health Service Center, 35-1, 5-chome, Shiba Minato-ku, Tokyo, Japan TI - CHROMIC INHALATION TOXICITY OF VINYL CHLORIDE MONOMER (MEETIf.'G ABSTRACT) 51 - HERN/02/15054 SO - Eighth International Conference of Occupational Health in the Chemical Industrv, Sept 22-25, 1900, Tokyo Permanent Commission and Internetional Association on Occupational Health, pp. S2-0I, 1900. LA - ENG AB - Two groups of Mi star rats, each consisting of 32 males and 32 females, were exposed to air containing 0 (control) and 3000 ppm winyl chloride monomer (VCN), 4, hr/day, 5 da"s/week for a period of 52 weeks. After' 13 and 26 weeks each time 3 male and 8 female rats per group and after 52 walks all altve animals were killed for detailed examinations on growth, mortality, hematology, clinical chemistry, organ weights and pathomorphology of various organs. By 26 weeks of exposu-e no significant changes were disclosed between the control and test animals. In The latter half of The experiment mortality of exposed rats rose gradually and of 32 tested rats 15 survived 52 weeks with Tumors in 14 00005531 VINYL CHLORIDE PAGE 3 rats, while in the control group all were alive with no malignant neoplasm. Primary neoplasms explaining causes of death were noticed in such various siTes as The lungs i liver, nasal cavity, ceruminous and mammary glands and so on. Besides in the Kidneys histological changes were found. Growth of exposed rats retarded slightly. Hematological and biochemical blood changes, however, were very slight even after 52 weeks except minor signs of anemia. In this study obvious parameter's for early diagnosis of VCM related changes could not be found, partly because our examinations aimed at detecting hepatic changes, that were revealed in only A rats, (no Refs) 5 AU - Fleig I I Thiess AN AD - BASF Aktiengesellscnaft, Occupational Medicine and Health Protection, 6700 Ludwigshafen, Rhine, U. Germany TI - CHP.CMOSCME ANALYSES IN* THE CHEMICAL INDUSTRY - PREVENTIVE METHODS IN OCCUPATIONAL MEDICINE (MEETING ABSTRACT) SI - HERN/82/15053 SO - Eighth International Conference of Occupational Health in the ChsMiical Industry, Sept 22-25, 1930, Tokyo Permanent Commission and Internat1onol Association on Occupational Health, pp. 5-10, 1930. LA - ENG AB - In 1970 chromosome analyses were started in the BASF Aktiengesellschaft on workers who could come into contact with lead or other' toxic substances, such as e thvlene l m l ne , benzene, dimethylsulpnate. These investigations were undertaken in order to determine whether or not chemical substances which possibly show a mutagenic effect in bacterial tests or animal experiments, can also cause mutations in human beings. The chromosome analyses were performed on lymphocytes which were cultured for 72 hours and then handled according to a modification of The Moorhead et al method. AT least 100 metaphrases per person were analysed. The following substances were examined: acrylonitrile, auramlne, benzene, ethy lene1 mine , aikylene oxides (ethylene oxide, propylene oxide and derivatives), ethylbenzene residue, dl-2-ethylhexylphthalate, dimethvlsulphate, lead, dimethylcarbamoylchior 1 da, ortho-phthalodinitr1le, styrene, dioxane, Tetrahydrofurane, tetrachlcrdibenzodioxin, vinyl chloride. Increased rates of chromosome aberrations were found in 1 case of angiosarcoma and 20 other workers from various German chemical plants (not BASF) due to vinvl chloride (VC )-exposure, in persons employed in plants processing unsaturated pols'ester resins (also not BASF) and in workers with longterm exposure to aikvlone oxides. The remaining cytogenetic studies showed no increased aberration rates, (no Refs) 00005582 VINYL CHLORIDE PAGE 9 6 AU AD TI SI SO LA AB 7 AU AD TI SI SO LA AB National Toxicology Program Box 12233, Research Triangle Park, NO, 27709 CARCINOGENESIS BIOASSAY OF BUTYL BENZYL FHTHALATE (CAS HO. 65-63-7) IN F399/N RATS AND B6C3F1 I1ICE (FEED STUDY), ICDB/82/32309 Natl Toxicol Program Tech Rep Ser. Issue 213, 98 pp., 1982. ENG A carcinogenesis bioassay of butyl bsnzvl phthalate, (B3P) a plasticizer for vinyl chloride plastics was conducted by feeding diets containing 6,000 or 12,000 ppm ESP to 50 F399/N rots and 50 E6C3F1 mice of each sex for 23-103 uk. Mean body weights of dosed female rats and mice of both sexes were lower than those of controls throughout most of the study. After uK 19, an increasing number of dosed male rats died of internal he.norrhag i ng, and all survivors were killed at uk 29-30, BBP could not be adequately tested for carcinogenicity in male F399/M rats. Mononuclear cell leukemias occurred at a statistically significant increased incidence in the high-dose group of female rats when compared with the control grouo, and with a signlficantly increasing trend. These results remained significant when compared with the historical incidence for F399/N female rats with leukemia. The leukoproliferation was generally characterlzed bv splenomegaly and often bv hepatomegaly. Administration of GBP was not associated with increased incidences of any type of tumor among male and female mice. Tumor rates were decreased in female rats for fibroadenomas of the mammarv glands and in male mice for lymphomas of the hematopoietic system and for a 1 veolar/bronch i ol ar adenomas or' carcinomas. Under the conditions of this bioassay, BBP was probably careinogenic for female F399/N rats, causinq an increased incidence of mononuclear cell leukemias. The male F399/N rat study was considered inadequate for evaluation due to compound-related toxicity arid early mortality. EBP was not carcinogenic for B6C3F1 mice of either sex. (97 Pefs ) Green M Chemical ProcurmenT for Res., Polaroid Corpora!ion, Cambridge, HA, 02139 SCIENTIFIC MCCARTHYISM. ICD3/82/30751 Chemtecn; 11(17)1902-906 1981 ENG Loss of objectivity in the filed of cancer research is discussed. Topics include the increased public awareness of environmental chemicals, government regulation without review of interpretation of experimental results, high- rather Than low-level experimental exposure and the need to establish threshold doses, danqer of extrapola11 on to low doses when curm shape is not known, use of cancer-prone test animals as models for human exposure, and the tendency to regard postive (even false-positive) results more highly than negative findings. The chemicals sodium nitrite, thlouracil, 6-nitro-benzlmidazoie, and vinyl chloride are used to 11 c > -.< SvA'--SS^triN *. 00005583 VINYL CHLORIDE 33 (/> co 00 (D 00 > ! PAGE 5 "a c c C. c <" V ' w,, - v >1 8 AU AO TI SI SO LA A8 9 AU AO TI SI SO LA AB illustrate certain points. Stress as a cause for increased cancer incidence is noted. Prediction of cancer in humans must be followed by validation of actual experience: dose-response at realistic levels of exposure, threshold level, and processes by which cancer develops need to be elucidated. (9 Refs) Juszczyk J Klinlka Chorob Zakaznych, Akademia Medyczna, ul. Uincentego 1, 61-003 Poznan, Poland ECOLCGIC PROBLEMS IN HEPATH0L0GY, CHRONIC LIVER DAMAGE DUE TO ENVIRONMENTAL FACTORS. ICDB/62/30742 Pol Arch Med Hewn) 67t3):101-112 1932 POL Studies on the harmful effects of environmental factors on the liver are reviewed after an outline of the biotransformation processes taking place in the liver. Substances with proven or suspected hepatocarcincgenic effects include mycotoxins, such as aflatoxlns, safrole, vinyl chloride, and active agents of oral contraceptives. Increased frequency of hepatic carcinoma was found in rats treated with 0.00C075X aqueous solution of a nitrosamine po compared with untreated controls. Liver scirrhoma, induced by many envircnmental agents, is a substrate for the development of hepatic carcinoma. (38 Refs) Hall JA ; Saffhill R Christie Hospital and Holt Radium Institute, Manchester, England CHLOROACETALDEHYOE, A VINYL CHLORIDE METABOLITE, INDUCES ERRORS DURING IN VITRO DNA SYNTHESIS (MEETING AB5TRACT) HERN/82/12891 Br J Cancer; 44(2)'-272 1981 ENG Chloroacetaldehvde (CA), a rearranged metabolic product of the human carcinogen vinyl chloride, has been shown to be mutagenic in certain microbial systems as well as towards mammalian cells. CA has been reacted with the alternating OMA-like polymers poly(dA-aT) and poly(dC-dG) when, as with DNA, eTheno-adduct3 of the adenine and cytosine bases are formed. These treated polymer's, when used as templates for Escherichia coli DNA polymerase I, show a decreased abilit" To direct DMA synthesis. This is accompanied by an increase in the relative levels of non-complementary nucleotides incorporated into the newly synthesized DNA-like material. This increased with the amount of modified base present in The Templates used. With the pol'MdA-dT) templates one dGMP (quanoslne monophosphate) residue was incorporated for every 60 + /- ethenoadenine residues present, while no dCMP (cytidine monophosphate) misIncorporation was detected. One mlsincorporation of cAMP or dTMP (Thymidine mcnophosphate ) occurred in the presence of 30 +/- and 80 +/ethenos'/1os 1 ne residues respectively in The poly(dC-dG) Templates. For The modified poly(dC-dG) templates, a nearest-neighbor analysis shows that the majority of the errors were incorporated opposite the cytosine (or modified eytosire) c c c c c L / Vu L 00005584 VINYL CHLORIDE PAGE 6 Bases. Extensive analyses of the modifications present in the templates indicate that the misincorporatlons observed are not due to The presence of epurimc slTes or to The formation of uracil or xanthine by deamination of the cytosine or adenine bases respectively. We conclude that The non-comolementarv nucleotide incorporations probably arise from the presence of etheno-adduct3 in The templates used, (no Refs) 10 AU - LaTar jot R AD - Institut Curiet Paris. France TI - QUANTITATIVE COMPARISON OF GENOTOXIC (MUTAGENIC AND CARCINOGENIC) RISKS AND THE CHOICE OF ENERGY SOURCES. SI - ICC3/82/2900Z SO - Bull Acad Natl Med (Paris); 166(21:181-201 1982 LA - FRE AB - The mutagenic and carcinogenic effects of pollution are discussed in relation to energy forms. The need for determination and Comparison of risks for various energy forms IS considered. Risks should be considered as both relative and absolute and in relation to both self and others. G-zno toxic risks include lethal, mutagenic, and carcinogenic effects, Khan considering the carcinogenic effects baseline statistics must be considered. In indusTrtalized countries. 20k of population will eventually die of cancer; another GZ will be cured of cancer. The system of rad-equI valences is considered in relation to the mutaaenic effects of vinvl chloride, formaldehyde, ethvlene, and ethylene oxide. Using The rad-egulvalerce concepts it is possible to extrapolate the rules developed for ionized radiation to determine persons at high risk for mutagenic effects of various chemicals. The system is particularly relevant for persons exposed to ethylene and ethylene oxide. The levels of pollution due to ethylene and ethylene oxide in France are described. It is recommended that controls be established for the main genotoxic chemical pollutants and That long term risks be assessed in relation to nuclear energy and energies obtained by combustion. (2 Refs ) 11 AU AD TI SI SO LA AB - Wallace D ; Nelson N ; Gates T - Public Interest Scientific Consulting Service, 549 W, 123 St., New York, NY, 10027 - POLYVINYL CHLORIDE WIRE INSULATION DECOMPOSITION II. CONSIDERATION OF LONG TERM HEALTH EFFECTS FROM CHLORINATED HYDROCARBONS. - IC03/S2/2S292 - J Co.-bust Toxicol! 9( fl.ev ): 105-112 1982 - ENG - Because of continued reports of new disorders in female suryIvors of the Bewerly Hills Sveper Club Fire and in the firef Iqhiers 'njured durinq the New York Telephone Fire and who were cn active duty 1978-June 1931, further studies of The posstble long-term healtn effects were conducted. All 12 women among The 50 injured survivors of The Beverly Hills Fire, who were of reproduc11 'e age (40 yp or less), responded To a letter of Inquiry. All co...plained c . (V- C7* JyJ/TfrAy* 00005585 VIMYL CHLORIDE JJ 99 (/) w 00 CD 03 O) PAGE 7 c of uterine dysfunctions: eight complained of heavy menstrual bleeding and three had hysterectomies. Two miscarriages occurred c but no other pregnancies or births. The 12 reported no such pre-fire problems. A total of six cancer cases were uncovered among the 700 firefighters involved in the New York fire. Cancer occurred in 4/6 cases in men less than 45 yr old compared to r 35/62 in the fire department as a whole for men greater than 45 yr old. Three of four cases of laryngeal/throat lesions resorted for the department ware in the exposed group. While the overall cancer incidence is only slightly higher for the cohort (857/100,000) than for the department (560/100,000), the age specific incidences are much higher if the assumption of similar age structure of the two populations is valid. The literature on the health effects of vinyl chloride monomer and chlorinated aromatic hydrocarbons includes reports on uterine dysfunction and occurrence of rare cancer types. The possibility that the presence of these compounds in the smoke may be producing or promoting the observed patterns is addressed. (16 Refs) (. 12 AU - Jones D3 ; Smith PM AD - Dept, Gastroenterology, Llandough Hosp., Penarth, 5. Glamorgan, England TI - PROGRESSION OF VINYL CHLORIDE INDUCED HEPATIC FIBROSIS TO ( ANGIOSARCOMA OF THE LIVER. SI - ICDB/32/23032 SO - Br J Ind Ned! 39(31:306-307 1982 LA - ENG AB - Two vinyl chloride monomer (VCM) workers, who developed non-cirrhotic portal fibrosis and portal hypertension , died from angiosarcoma of the liver 5 and 10 years later respectively, despite withdrawal from occupational exposure. We suggest that non-cirrhotic portal fibrosis caused by exposure to VCM is potentially premallgnant and that those workers who already have the condition should be carefully monitored. (Author abstract) (11 Refs ) 13 AU - Anderson D AD - BIERA, Woodmansterne Road, Carshalton, Enqland TI - THE PREDICTABILITY OF ANIMAL BIOASSAYS (MEETING ABSTRACT). SI - HEPN/82/19979 SO - Twelfth Annual Meeting of the European Environmental Mutagen Society, June 20-24, 1932, Dlpoli, Espoo, Finland, European Environmental Mutagen Society 250 pp., 1932. LA - ENG AB - Laboratory models which provide data for predicting the potential human mutagenic or carcinogenic risk of chemicals are short-term tests, animal studies or cellular responses combined with human exposures. The efficiency of The models can be Judged by their ability to predict a human mutagen or carcinogen, its potency and organ specificity. Cigarette Smoke, vinyl chloride, lead a^c anesthetic gases have the best documented evidence of possible mutagenic effects In man. There a'-e 26 agents which are knc~n To it produce cancer in man but only 19 of these are specific cne.micals 00005586 VINYL CHLORIDE PAGE 8 which are also Known To be animal carcinogens. Laboratory models ara generally judged on interspecies comparisons involving species other than man. Short-Term tests can have as high as 90'/. predictiviTy tor animal carcinogenicity but This is influenced by chemical selection and test conditions. Comparisons in rats and mice of careinogenicity data show these species to be 85X predictive for each other. About 60X of human carcinogens have The same target organ in man and animal studies. Sixty-five percent of chemicals carcinogens in rats and mice have a common Target organ in both species. Short-Term tests are not sufficiently developed To predict organ specificity. Potency correlations from short-term tests to animal models are subject to inaccuracies partly because of the variables associated with methods expressing dose and response in animal studies, (no Refs) 14 AU - Dent JG Graichen ME AO - Smith Kline and French Labcratories, P.0. Box 7929, Philadelphia, PA, 19101 TI - EFFECT Or HEPAT0CARCIN0GENS CM EPOXIDE HYDROLASE ANO OTHER XENOBIOTIC METABOLIZING ENZYMES. SI - ICD8/62/27564 SO - Carcinogenesis; 3( 7):733-730 1932 LA - ENG A3 - Hepatocarcinogens cause marked biochemical changes in the liver at short intervals after administration. The studies described were designed to investigate the effects of hepatocarcincgens and hepetotoxicants on the microsomal mixed function oxidase system, DT-diaphorase and epoxide hydrolase. Following 5 day po treatment of male F-344 rats with aflatoxm B1 (AFB), 2-acetylaminofluorene (AAF), technical grade diniTroToluene (DMT), or 2,4-diaminotolucne , microsomal cytochrome P45Q dependent enzyme activities were depressed while epoxide hydrolase activity was markedly elevated (3-8 times control). Di e th'jln t trosami ne (DEN) given a; 5 mg/kg/day and DL-ethlonine at 1,000 mg/Kg/day failed to increase epoxide hydrolase. 3-Methylcholanthrene, methylnltrosourea 1 carbon tetrachlor1de , bromobenzene and vinyl chloride all failed to increase epoxide hydrolase activity. Using 3 daily ip injections, dose-response relationships for increases in epoxide hydrolase were generated for the hepatocarcinosens. With The exception of p-dimeThylaminoazobonzene (DAS) and DEM, the carcinogens studied produced log-linear dose response curves for increase in epoxide hydrolase- Both DEN and DAB caused increased in epoxide hydrolase but classical sigmoidal dose-response curves were not obtained. The order of potency for increasing epoxide hydrolase was AFB much greater than AAF greater than ,6-din1trotaluene greater than 31-methy1-M,N-dime thy1-A-am1 noacobenzene qreater than DMT greater than 2.4-d1n1Trotoluene. The slopes of the linear portions of the log dose-response curves were not statistically different from the slope of The dose-response curve obtained with AAF suogesting that structurally diverse carcinogens elicit increases in eooxide hydrolase by a common mechanism. (Author abstract) (46 Refs) 00005587 VINYL CHLORIDE PACE 9 c 15 AU - Oesch F I Ooerjer G AO - Dept. Toxicologyi Univ. Mainz, Obere Zahlbacher STrasse 67, c D-6500 Mainz. U. Germany TI - DETECTION Or N2.3-ETHENOGUANINE IN DMA AFTER TREATMENT WITH CHLOROACETALDEHYDE IN VITRO. SI - ICD3/82/26769 c SO - Carcinogenesis! 3(6 1:663-665 1982 LA - ENG AB - The reaction of chloroacetaldehyde. a reactive metabolite of the carcinogen vinyl chloride, with DNA produces in addition to the hitherto Known adducts. 1.NS-ethenoadenlne and 3.N4-ethenocytosine. an etheneguanine adduct, namely N2,3-ethenoguanine. This adduct is formed in the reaction of chloroacetaldehyda with the free base as well. After DNA hydrolysis followed by isolation of this new adduct by hpic, its mass spectrum and fluorescence spectrum are identical with those published in the literature for the chemically synthesized N2,3-ethenoguanine. The formation of only this guanine derivative cut of several theoretically possible reaction products allous (. the formulation of a reaction scheme. The absence of .'-( 2-oxoethy 1 )-guani ne , another recently detected DNA adduct of viny chloride, in chloroacetaldehyde-treated DNA suggests its Origin from the other reactive metabolite of vinyl chloride, V chloroethylene oxide. The potential of N2.3-ethenoguanine to lead to m1s1neorperation of deoxythym1dine monophosphate opposite to guanine and the high fluorescence of this adduct provide it with potentially high biological significance and ease of analytical c monitoring. (Author abstract) (16 Refs) 16 AU - Malt oni C t Ciliberti A ; Carretti D AO - Inst. Oncology. Bologna. Italy / V. TI - EXPERIMENTAL CONTRIBUTIONS IN IDENTIFYING BRAIN POTENTIAL CARCINOGENS IN THE PETROCHEMICAL INDUSTRY. SI - ICDB/82/26015 SO - Ann NY Acad Scit 331:216-269 1902 LA - ENG AB - Incidence of brain tumors was studied in Sprague-Dawley rats treated by Inhalation at different doses of vinyl chloride (VC), vinyl I dene chloride (VDC). ethylene dichloride, acrylonltr1le (AC), styrene (ST), propylene. tr1chlorofluoromethane, dichlordifluoromethane . and chiorodifluoromethane. VC was also studied in some Ulster rats and for different times and schedules. Some compounds in olive oil were studied by qavage: VC, VDC, AC, ST, styrene oxide, vlnylidcnc fluoride, tr1ch1 oroethylene . benzene, asbestos (crocidoll te ). and polyvinyl chloride. VC and AC caused neurcb 1 as t o.as and gliomas (oligodendrogliomas), respectively, when given bv inhalation. Such effects were not seen at concentrat i ens of VC of 500 po-.> cr below and with AC at 10 ppm and below. This concentration-related effect on Tumor incidence appears less evident when total incidence is considered without regard to dose and Tvpe of Tumor. Under the conditions of The experimints, none of the compounds 00005508 VINYL CHLORIDE PAGE 10 17 AU AD TI SI SO LA AB 18 AU AD TI SI SO LA AO given by gavage produced brain Tumors. (11 Refs ) Wen CP i Tsai SP ( Gibson RL Gulf Science and Technology Co.. P.O. Box 2100. Houston, TX. 77001 A REPORT CM BRAIN TUMORS FROM A RETROSPECTIVE COHORT STUDY OF REFINERY WORKERS. ICC3/82/26007 Ann NY Acad Soil 381:130-138 1732 ENG Standardized mortality ratio (SNR) analysis was conducted for a Total of 17.521 employees of one full-service refinery in Texas, at which fuels, lubricants, and various petrochemicals> but not vinyl chloride, uere manufactured. Vital status was successfully determined for nearly 90X of the male employees I A,766 deaths uere recorded for the study period (1935-79). The owerall SNR for the population uas 0.89 for all causes of death, and 0.97 for malignant and benign brain neoplasms. There were 30 brain Tumor deaths. malignant, benign, or of unspecified nature; 25 in white males and 5 in nonuhite males'. The worker population was 17X nonwhite. Age at death for the 30 brain Tumor patients averaged 57.2 yr`, Th-. mean '/ear of hire was 193A; and the mean year of death was 1966. Length of employment for the group with brain tumors ranged from 8 days to A3 yr, with a mean of 23 vr. A preliminary survey of Job assignments of Those workers dying from brain tumor has not repealed any significant clustering compared to the total cohort. A separate study of AA3 benzene workers employed from 1952-76, 1,005 solvent-d-ewaxinq workers employed from 1935-76, and a control group of 2.1A0 workers at the same plant, revealed no significant excess brain cancer in any croup. There seems to be no significant increased risk of brain Tumor among workers at this Texas refiner''. I 10 Refs) Alexander V ; Let'fingwell S3 ; Lloud JW ; Uaxueiler RJ ; Miller RL Occupational Safety and Health Admin., Uni ted States Dept. Labor, Washington, DC, 20210 INVESTIGATION OF AN APPARENT INCREASED PREVALENCE OF DRAIN TUMORS IN A U. S. PETROCHEMICAL PLANT. ICDB/82/25056 Ann NY Acad Sci! 301:97-107 1902 ENG The occurrence of 20 primary brain cancer deaths amonq workers in a moderate-sized peTrcchemIca1 production facility in Texas prompted a cohort mortality stu-J' and a brain tumor case-control study. The av age at death was 55 yr and the total length of employment ranged from 1 mo t0 greater than 35 yr, with a median yalus of 19 yr. The inTeryal from first employment to death ranged from 3.5 yr to almost 36 >'r, wi th a median of 2A yr. All cases were males! 13 were white, 2 black. All but one were native-born Americans. Comparison with county primary brain tumor death statistics rawealed an approx plant-wide risk about 2< that of the county as a whole. Sixteen of the cases were identified as glioblastoma mu! TI forma. No com-cn Job title, department code, or chemical exposure could be found in careful preliminary c Zi c c * ,, ' , , "" f x-r--^x . -- - M 30 CO co oo to to o 00005589 VINYL CHLORIDE PAGE 11 exami nat i on of the work histories of the affected employees. Potential suspect agents which could be responsible for the unusual occurrence of brain cancer at this plant include vinyl chloride and diethyl sulfate; however, careful examination of the work histories did not support a significant positive association with vinyl chloride. These tumors are likely the result of occupational1chemlcal exposures since there is no good evidence implicating nonplant> general environmental factors as the cause of brain cancer excess. (57 Refs) 19 AU - Shibuva H ; Horiuchi J ; Suguki S I Takeda M A0 - Dept. Radiology) Tokyo Medical and Dental Univ, Sch. Medicine) Tokvp. Japan TI - REAPPRAISAL OF RADIOTHERAPY FDR LARYNGEAL CANCER USING TREATMENT CAST. SI - ICD3/62/25A60 50 - Nippon Igaku Hoshasen Gakkai Zasshi > A2(2 ):200-202 1932 LA - JPN AD - The use of vinyl chloride shells to improve the accuracy of radiotherapy for larvngeal carcinoma Is discussed with respect to 12 patients uho were treated using the shells and 21 who uere treated using a free sat up. An apparatus to automatical1v make the shells using a vacuum-forming technique was introduced. No large differences in dose received uere observed between the two groups. Edema was a complication in 3/12 shell patients and no complications were observed in the 22 free set up patients. On the other hand) no recurrence was observed 6-29 mo after treatment in the shell group while recurrence was observed 8-62 mo after treatment in the free set up patients. (9 Refs) 20 AU - Laib RJ ; Bolt HM AD - Internetional Agency for Research on Cancer, 69372 Lyon Cecex 2, France TI - INDUCTION OF HEPATOCELLULAR NUCLE0SI0E-5'-TRIPHOSPHATASE (ATPA5E ) DEFICIENT FOCI BY VINYL CHLOPIDE (VC) (MEETING ABSTRACT). 51 - HERN/32/17C16 SO - Proc Am Assoc Cancer Res", 23'-231 1932 LA - ENG AB - In many species including mani VC induces anqiosarcomas originating from endothelial cells of the liver, while in newborn rats, hepatocytes are more susceptible. This effect can be quantified by evaluating preneoplastic hepatocellu1ar foci with ATPase deficiency. Rats were exposed to 2G00ppm VC (8hrs/dav)> either transplocenta 1ly (schedule A) or immediately after birth for different time intervals (B-E), and from the ape of 21 days onwards (F). Four-month old animals were sacrificed and The livers evaluated histochemical!" for ATPase deficient foci. Transplaconta 1 exposure (A) and schedule D revealed no increase In ATPase deficient foci, possibly due to the low rate of VC metabolism at This developmenta 1 stage. The X foci Increased from schedule C to 0 but was not further enhanced after orolonqed exposure (E). Only a few ATPase deficient foci were ebserwed when exposure started 21 days after birth (F). As shown previously, a c c c c c c c. c L U Bo CO Co CD CO CO c 00005590 r- VINYL CHLORIDE c PAGE 12 c 70 day exposure of adult female rats to VC also did not result in ATPase deficient foe). These results indicate that the initiation c of preneoplastic lesions of VC in rat hepatocytes is restricted to the early lifetime and that VC does not exert a substantial growth-promoting effect on induced ATPase deficient foci. (1 Ref) 21 AU AD TI Air Pollution Control Association Pittsburgh* PA PROCEEDINGS OP THE INTERNATIONAL TECHNICAL CONFERENCE ON TOXIC c AIR CONTAMINANTS: HEALTH EFFECTS MONITORING AND CONTROL HELD IN NIAGARA FALLS, NY. 9-10 OCTOBER, 19S0. / c(. SI IC03/82/23623 SO Proceedings of the International Technical Conference on Toxic Air Contaminants: Health Effects Monitoring and Control held in Niagara Falls, NY, 9-10 October, 1930. Pittsburgh, Air Pollution c! Control Association, 297 pp., 1930. LA ENG AB Monitoring and control of toxic air contaminants were discussed in the following presentations: air pollution evaluation using cK. risk, assessment technology, potential model of care l nocenes 1 s and interpretation of short term tests, a working model of carcinogenesis and interpretation. Environmental Protection Agency (EPA) carcmoqen policy, developing neighborhood air \ concentration standards, measurement of perchloroeths'lene in ambient air, ambient air measurements of bencene in the bistate New York-New Jersey region, toxic and carcinogenic air pollutants in New Jersey (volatile organic substances), polynuclear aromatic hydrocarbon losses during high vol sampling, monitoring a chlorine spill, regulation of the incineration of hazardous wastes, control of vinyl chloride emissions in the Goodyear Niagara Falls polyvinyl chloride plant, problems and pitfalls of disposal of hazardous wastes, control technics for gas emissions from hazardous waste landfills, EPA regulation of atmospheric c carcinogens, and regulatory framework for setting air emission limits for non-crlterla pollutants, (51 Refsl 22 AU AO TI SI SO LA A3 Ribovich ML ', Miller JA ', Miller EC ; Timmins LG (c/o Miller) McArdle Lab. Cancer Res., l)niv. Ulsconsin Center Health Sciences, 950 North Randall Ave. , Madison, HI, 53706 LABELED 1,N(6 )-ETHENOA0ENO5INE AND 3,N<9 l-ETHENOCYTIDINE IN HEPATIC RNA OF MICE GIVEN (ETHYL-1.2-3H CR ETHYL-1-19CJ ETHYL CARBAMATE ( URETIIAN ). IC03/82/22605 Carcinogenesis; 3(5):539-596 1902 ENG Injection of a single dose of [ethy 1-1,2-3H) or (eth<'l-l-19C) ethyl carbamate into 12-da'/ old male (C578L/6 x C3H/He)Fl mice or of (e thy 1-1,2-3M) e thy 1 carbamate into adult male A/Jax mice resulted in the formation of labeled 1 ,N6-e thenoadenos i ne and 3 , N9-e tr.enoc v t i d 1 ne adducts in the hepatic RNA, These adducts were characterized by comiqrat1 on on hplc of 3H or 19C in enzymatic hydrolysates of the RNA with synthetic standards. Both the ethenoadenos1ne and ethenocyt1dine c L L L Vi O 0000S591 VINYL CHLORIDE JJ to CO 09 CD CO ro c PAGE 13 cc were further charactericed by their conversion to acetylated products that comigrated with acetylated synthetic standards. The ( cethenoadenosine was also converted by anhydrous trifluoroacetic acid to a product that comigrated with synthetic 1>N6-sthonoadenine. The levels of adducts in the hepatic RNA 12 hr after a single injection of 0.5-0,6 mg of ethyl carbamate/g body wt were 6-10 and 2-3 pmol/mg RNA of ethenoadenosine or c(' ethenocytidinei respectively. No labeled ethenoadenosine or ethenocytidine could be detected in the hepatic RNA of mice given C1-19C)ethanol> an engymatic hydrolysis product of ethyl carbamate. These data indicate that ethyl carbamate may be metabolically activated by dehydrogenation to vinyl carbamate and subsequent epoxidation of the latter compound as previously c proposed. Vinyl carbamate epoxide may form etheno derivatives in a manner analogous to that demonstrated for chloroethylene oxide, an electrophilic metabolite of vinyl chloride. Vinyl carbamate has been shown to have the same spectrum of tumor induction as c ethyl carbamate but to be much more active than the latter carcinogen, (Author abstract) (37 Refs) 23 AU - Jensen MM ; Chen I ; DeVault M ; Lewis AE AD - Department of Pathology, School of Medicine, University of California, Davis, CA ((. TI - ANGIOGENIC BREAST TISSUE AND SECRETIONS IN WOMEN (MEETING ABSTRACT) SI - HERN/82/13902 SO - 71st Annual Meeting of the International Academy of Pathology ( (United States-Canadian Division), March 1-5, 1982, Boston, Massachusetts. International Academy of Pathology 95 pp.< 1932. <9 LA - EMG AB - Ability to evoke new vessel formation is a property of malignant tissue. Angiogenic factor is a proposed marker for cancerous transformation. Histologically normal lobules and atypical c lobules (papillomatosis) were identified and isolated from fresh, sterile tissue stained with 2 mg per 100 ml of methylene blue chloride for 90 minutes at 9 C. Fragments, Transplanted onto rabbit irises, were observed for development of delicate vessels c around them. On day 5 they were processed for light microscopy. From 39 cancer-assoclated breasts, 92 of 150 normal lobules (28 per cent) and 22 of 37 atypical ioubles (60 per cent) were angiogenic. From 95 women with noncancerous breasts, 39 of 292 e normal lobules (13 per cent) and seven of 21 atypical lobules (29 per cent) were angiogenic. Thus, angiogenic parenchyma is more abundant in breast cancer patients. Breast cyst fluids were incorporated in eThy lone-"1ny1 acetate copolymer (Elvax 90, L Dupont) and implanted In rabbit corneas. Anqiogenesis , occurring in 12 of 21 samples, indicates secretion of angiogenic factor. LV. (no Refs ) 00005592 VINYL CHLORIDE PAGE 14 24 AU - Popper H ; MalToni C ; Selikoff IJ AD - STraTTon Lab. for The Study of Liver Disease. Mount Sinai Sch. Medicine. City Univ. New York, New York. NY TI - VINYL CMLORIDE-INDUCED HEPATIC LESIONS IN MAN AND RODENTS. A COMPARISON. SI - ICDB/82/21460 SO - Liver! 1(1):7-20 1931 LA - ENG A3 - Parallel sequences in the liver of man. rats, and mice exposed to vinyl chloride (VC) were comoared to review pathologic features induced, to document similarities in evolution from precursor lesions to malignant states, and To compare the evolution with that caused by other carcinogenic agents. Available for study were 19 human cases of angiosarcoma and precursor lesions following exposure to VC. previously reported, plus 5 additional angiosarcomas (autopsy) and 16 precursor lesions (biopsy material). Rats and mice had been exposed to VC in inhalation chambers. In man, the number of sinusoidal cells conspicuously increased and they almost filled the spaces between the enlarged hepatocytes. In rodents, the variety of sinusoidal cells was less conspicuous and fewer macrophages were found, but lining cells with large polychromatic nuclei similarly predominated. In man and rodents, progression of the sinusoidal dilatation associated with proliferation of the hepatocytes and sinusoidal cells loosened the parenchymal architecture. Nodules consisting of anqlosarcoma cells were noted in man and rodents. Most consisted of spindle-shaped cells, in part in vascular spaces which, however, in part were also lined by ncntumorous endothelial cells. In addition, in man. nodules consisted of large polyhedral sarcoma cells with abundant eosinophilic cytoplasm. The center of these nodules usually exhibited hemorrhagic necrosis and these cells then lined bloody cysts. The demonstrated similarity of the evolution in man and rodent strongly supports the extrapolation of observations from experimental animals to man. (53 Refs) 25 AU AD TI SI SO LA AB Pearson L ; Lindemuth E ; Witte EJ Gregg MB - Southeast Distric State Dept. Health, Montgomery County. PA - TRICHLOROETHYLENE EXPOSURE - PENNSYLVANIA." ICDB/OC/21160 - MMUR; 30(19):226.231-233 1961 ENG Effects of a trichloroethylane (TCE) spill in Montgomery County (PenneyIvania ) were investigated with respect to well and qround water in the community surrounding the plant where the spill occurred, in air samnles In the plant . in urinary excretion of TCE by workers exposed to TCE m the plant. The symptoms of TCE exposure in workers and controls were also examined. Levels of TCE were high in water. Time-welghtsd-av exposure to TCE vaoors decreased below NI03H recommended levels from February' to May. Seven of the nine workers exposed to TCE reported symptoms char ac t er 1 s t i C of acute TCE exposure. TCE is s tructurai 1'/ similar To vinyl chloride, but recent experimental data suggest That TCE c c ( l... "v. ." .. '.. (, ' 1 00005593 VINYL CHLORIDE PAGE IS may be a much weaker carcinogen than vinyl chloride. (5 Refs) 25 AU - Bycckowska Z AD - Klinika Chorob Zawodowychi Instytut Medvcyny Pracy u Prcemysle U'eglowym l Hutnicgym, ul, Bieruta 20. 91-200 Sosnowiee, Poland TI - DATA ON THE CARCINOGENICITY OF VINYL CHLORIDE. SI - ICDB/82/20073 50 - Pol Tyg Lek t 37(3)=95-97 1982 LA - POL AB - The case of a patient who developed solid hepatic adenocarcinoma after intermittent exposure to vinyl chloride (VC) for 17 yr is reported, and literature on the carcinogenicity of VC is reviewed. Hepatic angiosarcoma is considered a typical tumor developed from the exposure to VC. Other tumors, such as hepatoma, nephroblastoma, adenosarcCma, adenocarc1 noma , epidermoid carcinoma, and flbrcangioma were also observed in humans or experimental animals following exposure to VC. (3S Refs) 27 AU - Tamburro CH t Greenberg RA AD - Department of Medicine, University of Louisville, Louisville, KY TI - A REVERSE RELATIONSHIP BETWEEN EXPOSURE AND LATENCY IN CHEMICALLY INDUCED LIVER CANCER (MEETING ABSTRACT) 51 - HERN/S2/15599 SO - Aslan Pacific Association for the Study of the Liver and Internetional Association for the Study of the Liver, February 7-12, 1902, Kowloon, Hong Kong, Asian Pacific Association for the Study of the Liver and International Association for the Study of the Liver 110 pp., 1902. LA - ENG AB - It is generally believed that the latency period in cancer developnicnt is inversely correlated to the duration of exposure, ie, the longer the exposure, the shorter the latency. Vinyl chloride (VC) induced hepatic angiosarcoma (HA) in humans has allowed study of this relationship in 21 North American cases (NA) and 62 worldwide (WW) reported cases. In ail HA cases. VC exposure began between 1991 and 19661 92K of NA and W'W cases had long exposures ( LE) (10-33 yrs)", 7 cases (OX) had short exposures (SE) (3.5 to 7 yrs). The mean duration in both LE and SE groups was 10.5 yrs with two peaks at 15 and 21 yrs. All (100X) HA cases had qreater than 9 yrs latency (9 to 39 yrs) with Two peaks occurring at 15 and 25 yrs. Deaths from VC related HA began in 1955, increased to more Than one/yi' after 1967, peaked in 1976 and have rapidly fallen thereafter. Occurrence peaks were first reached in Canada in 1973 and in USA-1979, France-1976, and Germany-1976. Plant operations began In Canada In 19911 USA in 1939-99; France. 1991-57". and Germany, 1952-60. Reported exposure levels were in ranges of 2000 ppm in the 1990's". 200-500 ppm in 1950's ; 50-500 ppm in the oarlv 1960's and 50-250 ppm in the late '60's and early ' 70' s", and .`.bout 1 ppm after 1979. Individual latencies snowed a direct correlation between total exposu-e and clinical onset of HA, te> lower total exposure-shorter late-cy. This held true for SE and LE g-oups in both the NA and UU cases. (no Refs) 00005594 VINYL CHLORIDE PAGE 16 28 AU - Diets FK ; Re its RH ; Ua tana'oe PG ; Gehring PJ AD - Toxicology Res. Lab., Health and Environmental Sciences, Dou Chemical. 1803 Buildinq, Midland. MI, 48640 TI - TRANSLATION OF PHARNACOKIMETIC/BICCHEMICAL DATA INTO RISK ASSESSMENT. SI - ICDB/32/19435 SO - Adv Exp Med Biol; 136(partB):1399-1424 1932 LA - ENG A3 - Basic pharmacokinetic principles and biochemical mechanisms uhich must be considered in order to adequately evaluate the risk of exposure to man from potentially carcinogenic chemicals are reviewed. Dose-independent and dose-dependent pharmacokinetics are discussed. A theoretical model describing the pharmacokinetics of chemical interactions with macromolecules is presented, with emphasis on the importance of knowledge of the dose-related fate of a chemical and its macrcmolecular target site. Two basic mechanisms responsible for the observation of increased tumor frequencies in the typical animal bicassay are the genetic or genotoxic mechanism and the mechanism through which tumors are produced by a cytotoxic or nongenetic effect. Studies of vinyl chloride (VC) and chloroform illustrate the use of pharmacokinetic and biochemical data of the mechanisms of turnerigenesls to understand the differential carcinogenic response between species with emphasis on risk assessment. With VC. the incidence of hepatic angiosarcomas in humans can be predicted with reasonable accuracy using a probit percentage incidence model. The primary mechanism by uhich chloroform produces tumors in animal bioassays appears to be recurrent cytotoxicity accompanied by chronic tissue regeneration. The original risk estimation of chloroform was found to be unjustified and overestimated when the species dependent metabolic activation of the compound and the biochemical nature of chloroform-lnduced tumorigeniclty were considered. (33 Refs) 29 AU AD TI SI SO LA AD Guengerich FP Dept. Biochemistry, Center Environmental Toxicology, Vanderbilt Un 1v., Nashville, TN, 37232 METABOLISM OF VINYL HALIDES: IN VITRO STUDIES 0)1 ROLES OF POTENTIAL ACTIVATED METABOLITES. ICDB/82/19326 Adv Exp Med Biol-, 136( part A): 635-692 1932 ENG Mixed-function oxidation of toxic and carcinogenic vinyl halides IS thought to be responsible for the mutagenesis and Irreversible binding of metabolites observed with these cemoounds. One suggested reactive metabolite is a 2-haloethylene oxide, which in turn may rearrange to a 2-haloacetaIdehyde , both compounds reacting with nucleophilic Targets, Studies are reported examining the ability of purified enzymes to specifically destroy the postulated reactive intermediates of vinyl chloride and vinyl bromide in rat liver mtcrosoma1 systems, utiliclng irreversible binding of vinyl halide labels to protein and DMA as indices of 00005595 VINYL CHLORIDE PAGE 17 activation. The results are consistent with the view that, in the liver microsomal system, the 2-haloethylene oxides are The species predominantly involved in DMA binding. 2-Haloacetaldehydes> -formed from the 2-haloethylene oxides by halogen migration rearrangement> are The primary meTabolites binding To proTein and gluTathione. The 2-haloaceTaldehydes, being the more stable intermediates, probably play a significant role in binding to sites outside of the hepatocyte. (22 Refs) 30 AU - Pearson RB AD * Petrochemicals and Plastics Oiv., Imperial Chemical Industries Ltd., P.0. Box No. 6, Bessemer Road, Welwyn Garden City, Herts, England TI - PVC AS A FOOD PACKAGING MATERIAL. SI - ICDB/82/13527 SO - Food Chem; 8(2)-'85-96 1932 LA - ENG AB - Polyvinyl chloride (PVC) polymers used for food packaging, their physical properties, competitiveness with other packaging materials under current market conditions in Britain, their heat stability, their toxicity, and global migration are discussed. Because of the link between vinyl chloride monomer (VCM) and angiosarcoma, the max VCM level in all polymer for food packaging was reduced to 1 ppm`> the engineering and chemical modifications that were required to achieve this in PVC for bottle manufacture are briefly described, (no Refs) 31 AU - Chaklin AV ; Gritsiute LA AD - No affiliation qivan TI - CURRENT CONCEPTS OF THE ETIOLOGY AND PATHOGENESIS OF LUNG CANCER, SI - ICD3/62/I7669 SO - Vopr Onkol; 28(2):3-9 1932 LA - RUS AB - Literature data on the role of smoking and environmental pollutants in the etiology of lung cancer (LC) are reviewed. Epidemiological studies showed the relationship between the smoking and incidence of LC. LC morbidity in 95-69 yr old men increased from 1.9 per 100,000 for nonsmoKers to 5.9 for those who smoked 5 ciqare11es/day 13.5 for those who smoked 6-16 cigars11es/day , 29.5 for those who smoked 25-56 clgarettes/day, and 97.A for those who smoked greater than 56 cigareTtas/dav. Caroinoqenicity of tobacco tar is associated with the presence of polycyclic hydrocarbons , N-nitrosamines vinyl chloride, phenols, and various co-carc1 nogens. Recent studies showed the carcinogenic effect of 'passive' smoking. Increased LC morbidity in the reqions with intensive chemical industry indicates the co-carcinoqenic effect of such air pollutants as sulfur dioxide. Pathogenesis of LC is associated with the history of chronic lung inflammation, tuberculosis, scleroderma, exposure to asbestos, immunologic suppression, and individual activity of aryl hydroxylase. (95 Pefs) R&S 138997 00005596 VINYL CHLORIDE PAGE IS 32 AU - Greiser E 5 Re ini W ', Weber H AO - (c/o Rainl) GurlttsTrasse 53. 0-4000 Dusseldorf, W. Germany TI - VINYL CHLORIDE EXPOSURE AND MORTALITY AMONG GERMAN CHEMICAL WORKERS IN COMPARISON WITH MORTALITY AMONG NONEXPOSEO WORKERS AND PVC MANUFACTURING WORKERS. SI - ICD3/S2/17549 SO - Zentralbl Arbeitsmed ArbeiTsschutc Proph; 32(2 1:44-62 19S2 LA - GER AB - A historical prospective study compared mortality among workers in the German chemical industry. All workers studied were males of German or Austrian nationality. Three cohorts included 7,021 workers exposed to vinyl chloride monomer (VCM) and polyvinyl chloride (PVC). 4.910 chemical workers not exposed to VCM or PVC, and 4,007 workers exposed to PVC. Follow-up rate at the end of the study was approx 90X. The total male population of West Germany for corresponding yr served as controls. Standardised mortality ratios tSNR) showed no 'healthy worker effect' fcr PVC or VCM/PVC workers. SMR for malignant hepatic tumors was significantly higher than for controls. The increase was dose-cependent , Nonexposed workers showed a small increase in SMR /or hepatic malignancies. VCM/PVC worker shewed a significantly increased SMR for lymphatic and hematopoietic malignancies, PVC workers showed an increased SMR for malignant brain tumors. VCM/PVC, PVC, and nonexposed workers all showed on increased SMR for ischemic heart disease compared with controls. Because of long latencs' time for development of malignant tumors and the increasing incidence of hepatic hemangiosarcomas, additional follow-up studies of VCM/PVC workers are urged. (20 Refs I 33 AU - Bishop CS I Dye A AO - East Tennessee State Univ., Johnson City, TN, 37614 TI - MICROWAVE HEATING ENHANCES THE MIGRATION OF PLA5TICIZERS OUT OF PLASTICS. SI - ICDB/C2/17116 SO - J Environ Health; 44(51:231-235 1982 LA - ENG AB - The effects of the release of plasticicers from some plastic materials used in conjunction with food in microwave ovens are reviewed. While these plastics are not heated by microwaves, they are heated by conduction of heat from food to a point where the plasticlcars may be released; in one study this release amounted to 23'/. of the total weight. Two commonly used p las t i c I cars are d!-2-e thy Ihexyl phthalate (OEril), and d 1 - 2-e thy lhaxy 1 adipate (DEHA), One studv showed that mating of male mice given ip one-third of the LD50 of 0EHP wlth untreated virgin females at 12-wK intervals led to a reduction in the number of imp1 antations per pregnancy and litter sice. It was inferred that the early fetal deaths and semi s ten 11 ty constitute ad'-arse reproductive and genetic effects of 0EHP. Hepatic peroxisome proliferatlon in association with hepatomegaly were observed In animals treated with DEHP, DEHA., and 2-e t hy 1 hexano 1 bu r not with adipic acid or diethy1-phthalIde . Concerns over other types of onanges In 00005597 VINYL CHLORIDE 3J (fl 03 00 CO CO 00 r PAGE 19 cc plastics have been expressed in regard to vinyl chloride monomer, polyvinyl chloride, styrene monomer, and acrylonitrile monomer c cformerly used in soft drink containers. Various other healTh hazards from plasticizers are discussed. (32 Refs) 34 AU - Oesmet VJ AD - Pathologische ontleedkunde II, Academisch Ziekenhuis Sint-Rafael, B-3000 Leuven, Belgium TI - DRUG-INDUCED ALTERATIONS Or THE LIVER. HISTOLOGICAL ASPECTS. SI - ICDB/32/15372 50 - Acta Gastroenterol Belg! 44(9/10):367-374 1901 LA - FRE A3 - Histological characteristics of drug-induced liver disorders are described. Administration of methotrexate for psoriasis may result in hypertrophy and proiiferation of liver fibroblasts. Liver irradiation and urethane exposure can cause obliteration of centrolcbular veins. Liver adenoma, focal nodular hyperplasia, and hepatocellular carcinoma have been related to the chronic use of oral contraceptives. Exposure to vinyl chloride and ingestion of arsenic compounds has been related to the development of liver angiosarcoma. The differential diagnosis of cholestasis and other disorders, including Hodgkin's and non-Hodgkin's lymphomas is discussed. (3 Refs) c 35 AU - Gluszcz N A0 - Klinika Chorob Zauodouych, Instytut Hedycyny Pracy, ul. Teresy 6, 90-950 Lodz, Poland TI - DIFFICULTIES IN THE EARLY DIAGNOSIS OF LIVER DAMAGE DUE TO EXPOSURE TO VINYL CHLORIDE. 51 - ICDD/82/15197 50 - Med PrJ 32(4)1277-232 1931 LA - POL AD - Diagnostic tests were performed in 223 porkers exposed occupationally to vinyl chloride (200-1,000 mg/cubic mater) To detect poisoning. Acro-osteolys i s pas found in 5 cases, vascular disturbances in the extremities in 45. The alanine aminotransferase , aspartic am I notran:ferase, gamma-glutamyl transpspTldase , alkaline phosphatase, serum cholinesterase, bilirubin and proThrombin levels did not differ significant from those found in 70 unexposed controls. The Bromsulohalein test Pas positive in 9/50 and moderate hepatomegaly Pas found in 26/50 exposed porkers, (10 Refs) c c L 36 AU - Uronska-Mofor T ; Parke M t Laurman W AD - Instytut Medycyny Pracy, ul. Teresy 3, 90-950 Lodz, Poland C TI - BIOCHEMICAL CHANGES IN VINfL CHLORIDE POISONINGS. I. EFFECTS OF DIFFERENT VINYL CIIL0RI0E EXPOSURE CONDITIONS ON LIPID METABOLISM IN PATS. 51 - ICD3/32/15196 L- SO - Med Pr; 32(4)1247-253 1931 LA - POL AB - The effect of inhaled vinyl chloride (VC 50, 500 or 20,000 com, % T>--. -. exposure time 1-10 mo) on lipid metabolism pas studied in male 00005598 VINYL CHLORIDE PAGE 20 Uistar rats. Significant increases in the serum Triglyceride and phospholipid levels were found after 10-mo exposure To 20>000 ppm. Dose- and exposure time-dependence decreases were seen for cholesterol and especially for the triglyceride levels in liver but not in muscles> aortic wall and connective tissue. The findings indicate that disturbances in lipid metabolism play a minor role in the pathology of VC poisoning. (11 Refs) 37 AU - Suskov II ) Saronova LA AD - Inst. General Genetics, Acad. Sciences US$R> Moscow 117333i USSR TI - CYTOGENETIC EFFECTS OF ETOXY, PHENOLFORMALDEHYDE, AND POLYVINYLCHLORIDE RESINS IN MAN. SI - IC03/82/13426 SO - Mutat Res! 104C1-3 ):137-140 1982 LA - ENG A3 - Cytogenetic effects of synthetic resins were studied in workers exposed to epoxy and polyvinylchloride (PVC) in the manufacture of goods or to phenol and formaldehyde m The production of phenolformaldehyde (PF) resins. Chromosomal aberrations (CA) were analysed in peripheral lymphocytes from resin workers I av age 39.1 vr i exposure 9 mo-30 yr ) and healths' nonexposed controls. Exposure To the synthetic resins and their components was by inhalation and skin exposure. Av concentra*lon of chemical in the air was 6 mg/cubic meter (m3) for vins'l chloride. 1 mg/m3 for eplchlorohydrin (a component of eooxv resin). 0.3 mg/m3 for phenol, and 0.5 mg/m3 for formaldehyde. Among controls CA were found in 2.4/ of cells", 0.024 aberrant chromosomes (AC)/cell were found! 1.26 breaks/chromosomes were found. The frequency of CA in cells from exposed workers was 5.5/ for epoxv resin, 6.1/ for PVC, and 5.0/ for PF. Significant increases in AC/cell were found for all compounds. A significant increase in chromosomal breaks/cell was found only for PVC. Acentric single and paired chromosomal fragments were the predominant aberration noted, accounting for 90/. Results indicate the need for further study of the hazards of occupational exposure To synthetic resins and components of the resins. (5 Refs) 38 AU AD TI SI SO LA AB Hallstrom I I Maqnusson J ; Ramcl C - Dis'. Toxicology Genetics, Wallenberg Lab., Univ. Stockholm, Stockholm, Sweden - RELATION BETWEEN THE SOMATIC TOXICITY OF DIMETHYLNITROSAMINE AND A GENETICALLY DETERMINED VARIATION IN THE LEVEL AND INDUCTION OF CYTOCHROME P450 IN DROSCFHILA NELANOGASTEH. ICDB/82/12915 - Mutat Res; 92(1/2):161-168 1982 - Ei :g * Enzyme induction arid metabolism in Drosophila were studied with the use of somatic toxicity of d i me t hy In l t rosa-n i ne (DMN). The activity of cytochrome P450 (P450 ) in lnsec11c1 de-res 1stant Drosoohila me lar.ozas Ter (Hikone R and 5H5 strains) was higher than The P450 activity of insecticide-sensitive strains. Phenobarbital (FBI induced P450 in The sensitive strains but not in the resistant strains. The toxicity and mutagenicity of DMN c c ( I L' j.< c. 00005599 VINYL CHLORIDE PAGE 21 and the uptake of vinyl chloride (VC) were higher in the resistant strains than in the sensitive strains. The correlation between DMN toxicity and the metabolic differences between the insecticide-resistant and sensitive strains was demonstrated by the increased toxicity of CUM after F3 pretreatment in the sensitive strains but not in the resistant strains, A dominant gene i responsible for the patterns of VC and presumably C.`!N metabolism and the non-inducibi1ity of PASO in the Hikone R strain, was located in region 6b cM of chromosome 2, near the vg gene. This gene may be the major gene responsible for the insecticide resistance of the strain. Genetic variation in the mixed function oxidase system associated with insecticide resistance in Hikone R does not apply to the enzyme system as a whole. Benzol a Ipyrene monooxygenase activity and inducibility are the same in the insecticide-sensitive and Hikone R strains of Drosophila. (12 Refs) 39 AU - Hattis D AD - Center for Policy Alternatives, Massachusetts Inst. Technology, Cambridge, HA, 02139 TI - HEEDS FOR PUBLIC HEALTH INTERVENTION AND NEEDS FOR NEW RESEARCH CM VINYL HALIDES AND THEIR POLYMERS: A PU3LIC POLICY PERSPECTIVE. SI - ICDB/32/11072 SO - Environ Health Perspect; 91:227-231 1931 LA - ENG AB - Priorities for regulation and for research on the carcinogenic hazards of vinyl chloride (VC) and the related alkyl and vinyl halides, respiratory system hazards of polytvinyl chloride), and reproductive hazards of VC, are discussed. The most effective use of limited resources depends on deter'ml na t i on of the risk due to exposure under current standards and the likelihood of significant reduction in risk by revision of standards and enforcement . (8 Refs) 90 AU - Apfeldorf R ; Infante PF AD - Office Carcinogen Identification and Classification, Health Standards, Programs, Occupational Safety and Health Admin. U. S. Dept. Labor, Washington, DC, 20210 TI - REVIEW OF EPIDEMIOLOGIC STUDY RESULTS OF VINYL CHLORIDE-RELATED COMPOUNDS. SI - ICD3/B2/11071 SO - Environ Health Perspect; 91:221-226 1981 LA - ENG AB - Epidemiologic studies of structural analogs of vinyl chloride (VC) are reviewed. Analogs included eplchlorohydrin (ECU), trichloroethvlene (TCE), wlnylidsne chloride (VDC ), ethylene di bromide (EOD), oerchloroeth-'iene (PCS), and carbon tetrachlcrido (CC19). Occupational and Industrial uses of the Compounds include manufacture of epoxy resins (ECH) , copolymers and fibers (VDC), petroleum products (EDO), and pesticides (ED3). Other uses include metal degreasing (CC19, TCE, and PCE ) arid dry cleaning (PCE and formerly, TCE and CC19). Bloassays in experimental animals have demonstrated induction of Tumors at 00005600 VINYL CHLORIDE PAGE zz multiple sites by EDB and CC14, in the respiratory tract by EDB and ECH, and in the liver by VDC. EDB, TCE, FCE, and CC14. Studies of workers exposed to ECH or dry cleaning solvents suggest an increased risk of lung cancer, but the increase Is not significant, possibly due to sample sire. Studies of workers exposed to The other compounds have not given positive evidence of careinogenicity . All studios have been characterised by insensitivity to increases in mortality because of small sample sice. In some studies workers were exposed to more than one suspected carcinogen, making inTerpretat 1 on of results difficult. Estimation of qualitative risk To humans due To specific compounds should be based on experimental animal studies rather than on human epidemiological studies. (17 Refs) 41 AU - Chu KC i Milman HA AD - MCI, Bethesda, MD, 20205 TI " REVIEW OF EXPERIMENTAL CARCINOGENESIS BY COMPOUNDS RELATED TO VINYL CHLORIDE. SI - ICDQ/8Z/11070 SO - Environ Health Perspect; 41:211-220 1931 LA - ENG A3 - Results in carcinogenicity studies of vinylidene chloride (VDC), trichloroethylene (TCE), Te*rachloroethylene (PCE ), 1,2--dichloroethane (DCE), 1,2-dibi-omoethane (DBE), and epichlorohydrin (EPC), all structural analogs of vinyl chloride (VC), are reviewed. Bioassays of carcinogen)eity produced positive results with VDC in Swiss and CD-I mice and CD and Sprague-Dawley rats. Nonpositive results were obtained with VDC in Fischer rats and D6C3F1 mice. TCE given bv gavage or inhalation produced positive results in B6C3F1 mice. Nonpositive results were obtained with TCE in Sprague-Dawley and Osborne-Nendel rats. PCE given by gavaqe produced positive results in B6C3F1 mice and nonpositive results in Sprague-Dawley and Osborne-Mendel rats. DCE produced positive results in 66C3F1 mice and Osborne-Mendel rats when qlven bv gavage but nonpositive results in Swiss mice and Sprague-Dawley rats when given by inhalation. DOE produced positive results by gavage in B6C3F1 mice and Osborne-Mendel rats. EPC produced positive results in male rats and was an initiator of carcinogenesis when administered sc. Results indicate that compounds thought to act directly without metabolic activation produce tumors aT the site of administration, while those requiring activation do not. Important differences were found In response among 3pecies and strains. (21 Refs ) 42 AU AD TI SI SC - Vi anna MJ Brady J ', Harper P - Bureau Environmental Epidemiology, New York State Dept. Health, Tower Ouildinq, Empire State Health Placa, Albany, NY, 12237 - ANGIOSARCOMA OF THE LIVER: A SIGNAL LESION OF VINYL CHLORIDE EXPOSURE. - ICOQ/32/11069 - Environ Health Perspect; 41:207-210 1981 .'r;-<'**'`J*`jV t'`-?~*~'`i 30 Co CO w CO o o ro c 00005601 VINYL CHLORIDE PAGE 23 Cc AB - The association between exposure to vinyl chloride tVCM) and subsequent occurrence of angiosarcoma of the liver (A5L) is c creviewed. Although ASL is a rare tumor) some evidence suggests that incidence of ASL is increasing. ASL occurs more frequently among workers occupationally exposed to VCM than among the general population. ASL may also be related to low-level) nonoccupatlonal exposure to VCM, Other disorders possibly associated with exposure to VCM include cancers of the digestive) respiratory, neurologic, and lymphatic systems. (39 Refs) c 93 AU - Oimmick UF A0 - Emission Standards and Engineering Qiv. (MQ-13), U, S. Environmental Protection Agency, Research Triangle Park, NC, 27711 T1 - EPA PROGRAMS Or VINYL CHLORIDE MONITORING IN AMBIENT AIR. SI - ICDB/02/11068 50 - Environ Health Perspect', 91:203-206 1981 LA - ENG AB - Three studies detected vinyl chloride (VC) in the air around plants manufaeturing or using VC. An initial monitoring survey detected VC in the air around plants producing polytvinyl chloride) (PVC). A second program found maximum 29-hr concentrations of 0.32-10.6 ppm in open air; a relationship was found between VC in the air and certain emission excursions, A third study found less VC in The air around PVC fabricating plants than in the air around VC and PVC production plants. (5 Refs ) c 99 AU - Fabricant JO ; Legator MS AD - Oeot. Preventive Medicine and Community Health, Div, Environmental, Toxicology Unlv. Texas Medical Branch, Galveston, TX, 77550 TI - MUTAGENICITY STUDIES OF VINYL CHLORIDE. 51 - IC0B/32/11067 50 - Environ Health Perspect! 91:189-193 1931 LA - ENG AB - Studies of the mutagenicity of vinyl chloride (VC) in man and test organisms are reviewed. In vitro studies have demonstrated mutagenicity in both prokaryotic and eukaryotic orqanisms. In vivo studies of cytoganeric effects in animals and humans have demonstrated somatic and germinal mutations. VC hazards and the consequences of mutations are discussed. (26 Refs) c c c 95 AU - Rice JM AO - Perinatal Carcinoqenesis Section, Lab. Comparative Careinoqanasis , NCI, Fort Detrlck, Frederick, MD , 21701 TI - FREMATAL SUSCEPTIBILITY TO CARCINOGENESIS BY XEHOBIOTIC SUBSTANCES INCLUDING VINYL CHLCI0E. 51 - ICOB/32/11066 S0 - Environ Health Perspect! 91:179-108 1981 LA - EN3 AB - Principles of transplacental carcinogenesis and prenatal susceptibility to vinyl chloride (VC) and related compounds are reviewed. Positive results of bioassay for carc1 nogen 1city are c_ L 00005602 VINYL CHLORIDE PAGE 26 c indicated by a dose-related increase in incidence of tumors of one or more organ systems, a dose-related increase in multiplicity of tumors i or a shortening of latency periods. The c largest number of carcinogens are small organic molecules> many of which share similar mechanisms of action. Most carcinogens require metabolic activation. The most common metabolic pathway c for activation of carcinogens involves mixed-function oxidases. Assays of transplacental careinogenicity must insure that exposure by other routesi such as through the mother's milki is excluded. Studies in rats and mice have demonstrated that various compounds i including vinyl chloride tVC)> are capable of transplacental carcinogenesis. Studies indicate that the nonhuman primate fetus is susceptible to carcinogens earlier in gestation than the rodent fetus> and different tissues are affected. Analogs of VC would be expected to have activities similar to VC. l Mo evidence has been found suggesting that exposure of males to carcinogens leads to carelnogenesls in offspring of those males. (26 Refs ) 66 AU - Li 1 i s R AD - Environmental Sciences Lab., Dept. Community Medicine, Mount Sinai Sch. Medicine, City Univ. Mew York, One Gustave Levy Place, Mew York, NY, 10029 TI - REVIEW OF PULMONARY EFFECTS OF P0LY(VINYL CHLORIDE) AND VINYL CHLORIDE EXPOSURE. SI - ICDB/B2/11065 SO - Environ Health Perspect; 61U67-169 1931 (. LA - ENG A3 - Reported pulmonary effects of polyivinyl chloride) tPVC) dust are reviewed. Inhalation of PVC dust produces a granulomatous reaction, with inclusion of PVC particles in macrophages and histiocytes and interstitial pulmonary fibrosis (IPF), leading to exertional dyspnea, diffuse micrcncdular radiographic opacities of the chest, and restrictive pulmonary dysfunction. IPF after exposure to vinyl chloride (VC) mav be caused by alteration of proteins by VC and resultant immunologic reactions. VC is associated with increased incidence of lung cancer. (27 Refs) 67 AU - Maxweiler RJ ; Smith AH Falk H ; Tyroler HA AD - Industry-wide Studies Branch, Div. Surveillance, Hagard Evaluations and, Field Studies Natl. Inst. Occupational Safety and Health, 6676 Columbia Parkway, Cincinnati, OH, 65226 TI - EXCESS LUNG CANCER RISK It) A SYNTHETIC CHEMICALS PLAMT. SI - ICDB/02/11066 SO - Environ Health Perspect; 61:159-165 1931 LA - ENG AB - The occurrence of King cancer among workers employed at a synthetic chemicals plant at any time during the period 1962-1973 retrcspecTive cohort studv included 6,306 males. Of these, 6,176 were alive at the time of the study and 73 were lost To follow-up but assumed to be alive. At the end of the period studied only 30X of the cohort would have been greater Than 56 yr old! 63X had the opportunity to achieve 20 yr latency. When all employees were 33 fio (/) CO CD o O iS J-,". ^.Wwy-v ; J ,\VJ ?;.. ;%^i `."'S ( ^' .--. c c 00005603 VINYL CHLORIDE PAGE 25 considereed to be at risk from the start of employment at the plant> The standardized mortality rate (SNR ) was *ignificantly elevated for malignant neoplasms of the CHS (5MR 209) and respiratory system (SMR 149). When employees were considered at risk only after 10 yr of employment, results were similar buT the STIR was slightly higher. Excess lung cancers were not due solely to exposure to vinyl chloride (VC). A case-comparand study of 27 Workers with lung cancer indicated That large-cell undifferentiated type lung cancer (LCLC) occurred more frequently among workers (30k) than among comparands from the community l10k) with lung cancer. Among workers the risk of lung cancer was primarily for LCLC and adenocarcinoma. Analysis of exposure to Various chemicals using a serially additive expected dose model indicated polytvinyl chloride) dust as the most likely etiological agent. The next most likely aqent was vinylidene chloride. Latency time peaked at 5-16 yr. (27 Refs) 48 AU - tiolina G ', Holmberg B ; Elofsson S ; Holmlund L ; Moosing R AU - Westerhoim P AD - Occupational Toxicology Unit, Oeot. Occupational Medicine, Labor Medicine, Div. Dept. Occupational Safety, Box 100, 26 Stockholm, Sweden TI - MORTALITY AMD CANCER RATES AMONG WORKERS IN THE SWEDISH PVC PROCESSING INDUSTRY. SI - ICDB/02/11063 SO - Environ Health Perspectl 41:145-151 1981 LA - ENG AB - Mortality and cancer rates were studied among workers emploved in the Swedish polyvinyl chloride (PVC) industry for at least 3 mo in the period 1945-1974. Exposure To vinvl chloride (VC) was classified as high, medium, or low. A total of 2,073 workers were Surveyed, of whom 103 could not be followed up. Workers were divided into four study cohorts according to length of exposure and follow-up times. When compared with the national mortality rate, no significant increase was found for the total cohort or for any of the study cohorts. A shift in the cause of death compared with the national average was found. The freouency of myocardial infarction was higher during exposure or within a snort time after the end of exposure to VC. The frequency of death due to tumors was apparently hiqher in individuals with lonq latency times, but no significant difference was found. Although VC has not been proven a cause of mvocardial infarction, the relationship should be considered. The size of two of the study cohorts was too small to permit conclusions regarding the relationship between risk of mvocardial infarction and exposure level. 110 Refs ) c c c c L C L L c c c c -. c ( (, 00005604 VINYL CHLORIDE c PAGE 26 49 AU - Jones JH AD - Div. Surveillance> Hazard Evaluations and Field Studies. Natl. Inst. Occupational Health and Safety. 4676 Columbia Parkway, Cincinnati, OH, 45226 TI - WORKER EXPOSURE TO VINYL CHLORIDE AND POLYIVINYL CHLORIDE). SI - ICDS/82/11061 SO - Environ Health Perspect) 41:129-136 1981 LA - ENG AB - Industrial hygiene studies were conducted among workers at three vinyl chloride (VC) monomer (VCM) plants, three vinyl chloride polymerization (VCP) plants, and seven polyvinyl chloride (PVC) fabrication plants. Exposure to VC was highest among VCP workers and lowest among PVC workers. One Job category at VCM plants had exposures greater than 1 ppm. The highest av exposure was 22 ppm. Later studies have shown undetectable levels of VC, although in several cases levels greater Than Ippm were found. (36 Refs) 50 AU - Baxter PJ AD - Chronic Diseases Div., Special Studies Branch, Canter Disease Control, Atlanta, GA, 30333 TI - THE BRITISH HEPATIC ANGIOSARCOMA REGISTER. SI - ICDB/82/11060 SO - Environ Health Perspect) 41:115-116 1981 LA - ENG AB - A register has been established to record cases of hepatic anqlosarcoma (HAS) in Britain. Thirty-five cases of HAS in patients dying during The period 1963-1977 have been confirmed. HAS was related to exposure to vinvl chloride monomer (VCtt) in two cases and to ia administration of Thorotrast (a colloidal suspension of thorium dioxide) m eight cases. Two additional cases associated with exposure To VCM were confirmed in 1973-1979. (7 Refs ) 51 AU AU AD TI SI SO LA A3 - Falk H ; Herbert J i Crowley S ", IshaK KG ) Thomas LB ) Popper H - Caldwell GG - Chronic Diseases Div., Center Environmental Health, Centers Disease, Control, Public Health Service U. S. Dept. Health and Human Services, Atlanta, GA, 30333 - EPIDEMIOLOGY OF HEPATIC ANGIOSARCOMA IN THE UNITED STATES: 1964-1974. - ICD3/32/11059 - Environ Health Perspect) 41:107-113 1981 - ENG The occurrence of hepatic anqiosarcoma (HAS) in the Uni Ted States was studied for the period 1964-1974. Death certificates were reviewed in 22,432 cases of death due To lls'er tumors. Based on examination of medical records and pathological specimens. 168 cases of HAS were confirmed. Of cases identified as HAS on death certificates, only 42X were confirmed as HAS by other evidence) 50k were confirmed as not HAS. Only 23k of confirmed cases of HAS would have been identified by a search of death certificates alone. Inadequacies in epidemiological studies are indicated. HAS c 3J CO CD <D O 0 01 L ( c L C L C c ( ( (. ...... ' . ` :'>v-'j , C. '. (.. (_ 0000560S VINYL CHLORIDE ( PAGE 27 52 AU AD TI SI SO LA AB 53 AU AD TI SI SO LA AB occurred predominantly in men (male' female ratio 3:1) and more frequently in the younger age groups. The mean age was 50.1 yr for women and 57.9 yr for men. Of 127 men with HAS. 12 had been exposed to vinyl chloride (VC). 15 to Thorotrast (TT), A to inorganic arsenic (A3), and 3 to androgenic-cnabolic steroids (AA5); 93 cases were classified as idiopathic. Of 91 women with HAS, 5 had been exposed to TT. 2 to As, and 1 to AAS; 33 cases were classified as idiopathic. A relationship between HAS and VC. TT, or AAS was more common in the latter part of the study period, probably due to recent introduction of VC and AAS and a long latency period for TT. The mortality rate for HAS was 0.75 Cases/10(7) population/yr. The mortality rate was apparently higher in industrialized areas of the Northeast and Midwest and lower in farming states and the South; differences in rates for different areas may have been due to reporting methods rather than to actual differences in occurrence. Four agents have been identified as probable cau3ati"e factors in HAS, but 75X of cases are of uncertain etiology. (23 Refs) Cooper WC 2150 Shat tuck Ave.. Suite 901, Berkeley. CA, 99709 EPIDEMIOLOGIC STUDY OF VINYL CHLORIDE WORKERS: MORTALITY THROUGH DECEMBER 31, 1972. IC0B/Q2/11053 Environ Health Perspect; 91:101-105 1931 ENG A survey of the vital status of 9.677 men working for at least 1 yr with probable exposure to vinyl chloride monomer (VCM) showed that 707 workers had died. Standard 1 zed mortality ratios (SMR) calculated for 699 deaths were 89 for all causes and 109 for malignancies. The only types of malignancy found in significant excess were neoplasms of the brain and other parts of the nervous system: 5.9 deaths were expected but 12 occurred, for an adjusted SMR of 203. No significant differences were found among workers with less than 20 yr, greater than 20 yr, or greater than 25 yr exposure To VCM. (6 Refs) Weber H I Reinl W ! Greiser E StaaTllcher Gewerbeargt , Dusseldorf, W. Germany GERMAN INVESTIGATIONS ON MORBIDITY AND MORTALITY OF WORKERS EXPOSED TO VINYL CHLORIDE. ICDB/02/11057 Environ Health Perspect; 91:95-99 1931 ENG Morbidity and mortality among workers of German or Austrian nationality exposed to vinyl chloride monomer (VCM) were studied. Standard!red mortality ratios (5MR ) were calculated. SMR for workers exposed to VCM were compared with those for the West German male population, chemical workers not exposed to VCM. and workers e-posed to polyvinyl chloride (PVC ). Cause of death could not be determined in 7.3-13.IX of cases. Data from VCM and PCV workers did not show a 'healthy worker' effect. Among VCM workers, SMR were elevated for malignancies of the lymphatic and c c 3R0 Ui -j. w ID O O O) k c c c. L k_ 00005606 VINYL CHLORIDE PAGE 28 hematopo i et i c systems and for malignancies of The gastrointestinal (GI) tract. The increase in SNR for GI cancers was due to an increase in deaths due To liver cancers, SNR for liver cancers was also somewhat elevated for workers not exposed to VCN! cause of the elevation was uncertain. SNR for ischemic heart disease was elevated for all three grouos of workers. SMR for liver cancers increased with time of exposure to VCM, suggesting a time-response relationship. A dose-response relationship could not be established due to lack of dose determinations . SNR for cancers m general and for liver cancers were particularly high for men 35-44 yr old. A study of morbidit indicated 269 cases of suspected occupational disease among 6.50 workers in VCN or PVC production and 42.800 workers in PVC processing, (2 Refs) c c c DcO CO 54 AU - Infante PF AD - Office Carcinogen Identification and Classification, Health Standards. Program, Occupational Safety and Health Admin. U. S. Dept. Labor'. Washington, DC. 20210 TI - OBSERVATIONS OF THE'SITE-SPECIFIC CARCINOGENICITY OF VINYL CHLORIDE TO HUMANS. SI - ICD3/02/11056 SO - environ Health Perspect; 41:89-94 1931 LA - EN3 AB - Studies of site-specific carcinogenicity of vinyl chloride (VC) are reviewed. Problems encountered included relative insensitivity to carcinogenic response at low risk sites due to small sample sice, and characTer Istics of method and design that prevent adequate interpretation of results. Restriction of disease definition resulted in obscuring some sites that might otherwise have shown significant excess risk. Four of eight studies indicated a significant risk of liver csneer following exposure to VC, although the liver had been confirmed as a site of VC-carclnogenesis by other studies. Problems with studies of liver cancer included Insufficient exposure and observation times. Some studies classifv liver cancer with other cancers of the digestive tract. Overall data from at least one study of cancers of the digestive Tract indicate a reduction in mortality among exposed workers . An excess of mortality due to CNS cancers was indicated by five of eight studies. Soma studies classified CNS cancers with nonspecific 'other1 categories. Data for lung cancer mortality suggest a significant increase in risk for workers exposed to VC, Data for cancers of the lymphatic and hematopo i e 11 c systems are sucgestive but not conclusive. O'-erall data indicates that The carcinogenic effect of VC is not limited to the liver. (12 Refs) 03 CD O O c c c L C 00005607 VINYL CHLORIDE PAGE 9 55 AU - Hal ton I C ; Lodi P AD - Inst. Oncologyi Bologna, Italy TI - RESULTS OF SPUTUM CYTOLOGY AMONG WORKERS EXPOSED TO VINYL CHLORIDE MONOMER AND TO POLYlVINYL CHLORIDE). SI - ICDB/S2/11055 SO - Environ Health PerspectJ 91:35-88 1981 LA - ENG AB ~ Systematic cvtological examinations of sputum were performed in 3330 workers exposed to vinyl chloride monomer (VC)i some of whom were also exposed to polvtvinvl chloride) (PVC). Results were compared with those from 2,237 workers in other industries with different potential risks. VC-PVC workers had a higher incidence of cellular abnormalities and dvsplaslas in the respiratory tract than other workers. Results suggest a risk of upper respiratory oncogenesis among VC-PVC workers. (5 Refs) 56 AU AU AD TI SI SO LA AB Hehir RM ; McNamara BP I McLaughlin J I Milligan DA ! Bierbower - Hardisty JF U. S. Consumer Product Safety Ccmmission, Westwood Towers Building, Room 738, 5901 West Blvd., Washington, DC, 20207 CANCER INDUCTION FOLLOWING SINGLE AND MULTIPLE EXPOSURES TO A CONSTANT AMOUNT OF VINYL CHLORIDE MONOMER. ICDB/82/11059 Environ Health Perspect; 91 .'63-72 1981 ENG The effects of total dose and frequency of exposure on careinogenes i s of vinyl chloride monomer (VCM) were studied in Fischer 399 and Sprague-Dawley rats and A/J and ICR mice. Fischer rats and ICR mice were exposed to a single dose of 50, 500, 5,000, or 50,000 ppm VC for 1 hr. Fischer rats and A/J mice usee e.xposod lOx To 500 ppm VCM (1 hr/day, 5 ctay/uk for 2 uk ) or 100X to 50 ppm (1 hr/day, 5 days/wk for 20 wk). Sprague-Dawlev rats were exposed to 50-500 ppm VC (1 hr/day, 5 days/wk for 10 wk). All test animals were observed until sacrifice (13-29 mo). Animals were killed when moribund or on schedule. Significant toxic effects were observed only at 50,000 ppm. VCM produced dose-related increases in the frequency of pulmonary adenomas and carcinomas in mice at concerntrations of 5,000 and 50,000 ppm. Multiple exposures of A/J mice to 500 ppm produced significant increases in occurrence of pulmonary adenomas and carcinomas. Multiple exposures to 50 ppm did not produce significant increases in occurrence of the tumors. Carcinogenic effects were not observed in rats at the total VCM doses used. Results indicate that careinogenesis depends on total dose but concentre11 on may be the most critical factor in short-term exposure. Single exposure required at least 5,000 ppm-hr In mice or 50,000 ppm-hr in rats for carcinogenesis. Mice were more sensitive than rats to VCM. (10 Refs) 30 (/> co ID O O 03 c t e c .: .i c 0000560S VINYL CHLORIDE c PAGE 30 r 0 ( ` (. ( 57 AU AD TI SI SO LA A8 Radike HJ ; Steimner KL 1 Bingham E Dapt. Environmental Health, Kettering Lab., Univ. Cincinnati Medical Center, 3223 Eden Ave., Cincinnati, OH, 45267 EFFECT OF ETHANOL ON VINYL CHLORIDE CARCINOGENESIS. ICDB/82/11053 Environ Health Perspect; 41:59-62 1981 ENG The potential cocarcinogenicity of ethanol uith vinyl chloride (VC) was studied in male Sprague-Dauley rats. A Total of 320 rats (80 rats in each of four groups) mere studied: Group 1 was exposed to VC (600 ppm, 4 hr/day, 5 days/uK for 1 yr), Group 2 was exposed to VC and ethanol (52 in water, beginning 4 wk before the start of VC exposure and continuing for life), Group 3 was exposed only to ethanol, and Group 4 was exposed only to filtered air. AT 13 mo rats exposed to VC showed an av weight loss of approx 92. At 18 mo the survival rate was 402 for Group 1, 182 for Group 2, 732 for Group 3, and 702 for Group 4. Angiosarcomas were found in 232 of Group 1, 502 of Group 2, and 02 of Groups 3 and 4. Hepatocellular carcinomas were found in 442 of Group 1, 602 of Group 2, 102 of Group 3, and 02 of Group 4. Lymphosarcomas were found in all groups but most frequently in Group 2, Endocrine tumors were found in 57 rats in Group 3, compared uith 29 in Group 1, 30 in Group 2, and 8 in Group 4. Some rats developed more than one angiosarcoma or carcinoma. Results indicate That ethanol has a strong cocarcinogenic effect in rats exposed to VC. (8 Refs) 58 AU AD TI SI SO LA AD Groth DH I Coate h'3 I Ulland DM I Hornung RW Div, Biomedical and Behavioral Science, Natl. Inst. Occupational Safety and Health EFFECTS OF AGING Oft THE INDUCTION OF ANGIOSARCOMA. ICDB/82/11052 Environ Health Perspect; 41:53-57 1981 ENG The effects of aging on chemical induction of angiosarcoma were studied in adult Spraque-Dawley albino rats. In each of four age groups (6, IS, 32, and 52 wk old at the start of exposure), 110-128 male rats and an equal number of female rats were exposed to vinyl chloride (VC: 948 ppm, 7 hr/day, 5 days/wk for a mean duration of 24,5 wk ). Equal numbers of controls were kept under identical conditions but were not exposed to VC. Rats exposed to VC did not show any significant differences in mean hematological of' clinical chemistry measurcments at interim sacrifice Tines when compared with controls. Anqiosarcomas were found in 28/370 exposed males and 50/337 exposed females! a>nonq Controls only one sc angiosarcoma was found. Anqiosarcomas occurred more frequently with increasing aqe at the start of exposure. Among male rats killed at unscheduled times, the occurrence rates were 02 for 6-wk-, 02 for 17-wk-i 6.72 for 32-wk-, and 242 for 52-wk-old rats. The corresponding rates for female rats were 5.32, 152, 472, and 202. Times between start of exposure and first appearance of tumors were shorter in older rats than in younger c c c c c 33 R 03 CO CD O O CD c c c L L c IS C* 00005609 VINYL CHLORIDE PAGE 31 c ;' C t ';:, u--.'-.i -V '>.< `'' rats. Most of the engiosarcomaj in exposed rat were highly anaplastic primary tumors of the 1iver with pulmonary metastases. Results indicate that older rats and female rats are more susceptible to induction of angiosarcomas by VC than younger rats and female rats, respectively. (3 Refs) 59 AU - Suguki Y A0 - Environmental Sciences Lab., Dept. Community Medicine, Mount Sinai, Sch. Medicine City Univ. New York, One Gustave Levy Place, New York, NY, 10029 TI - NEOPLASTIC AND N0NNE0PLASTIC EFFECTS OF VINYL CHLORIDE IN MOUSE LUNG. SI - ICDB/82/11051 SO - Environ Health PerspectJ 61-'31-52 1981 LA - ENG A8 - Careinogenicity of vinyl chloride (VC) was studied in the lungs of CDI Charles River white strain mice. Of 27 mice, 6 were exposed to VC (2,500 or 6,000 ppm) for 5 hr/day, 5 days/wk for 5 mo and killed after a 6-day period without treatment. Thirteen mice were exposed to VC (2,500 or 6,000 ppm) for 6 mo and killed 2 days after the end of treatment. Eight mice were exposed to VC (2,500 or 6,000 ppm) for 6 mo and killed after a 37-dav recovery period. The effects of lower doses (0, 1, 10, or 100 ppm, 5 hr/day, 5 days/wk for 6 wk ) were studied in 120 mice. Pulmonary tumors were found in 26/27 mice treated with the higher doses. Tumors Were multiple and either tubulo-papi1lary or adenomatous. No metastases were found. Electron microscopy showed short microvilli, tight junctions between adjacent cells, osmiophilic lamellar bodies, large irregular mitochondria, wel1-developed Golgi complexes , continuous or discontinuous basement membranes, occasional sequestration of crystalloids, and lack of cilia and secretory granules. Tumors were classified as alveologenic, possibly developing from hyperplastic Type II alveolar epithelium. Nonneoplastic effects included pro!iferation and hypertrophy of bronchiolar cells, abnormal mItochondria , and proliferation of rough endoplasmic reticulum. Low doses of VC produced tumors in 5/9 mice at 100 ppm, 2/9 at 10 ppm, 1/9 at 1 ppm, and 0/10 at 0 ppm. Results indicate that VC induces pulmonary tumors in mice in a dose-related fashion! mouse lung Is a sensitive indicator of VC careinogen Ic1ty , (52 Refs) 60 AU - Maltoni C I Lefemine G t Ciliberti A t Cotti G t Carretti D AD - Inst. Oncology and Tumor Center, Dologna, Italy TI - CARCINOGENICITY QI0A5SAYS OF VINYL CHLORIDE MONOMER: A MODEL OF RISK ASSESSMENT CM AN EXPERIMENTAL BASIS. SI - ICDD/02/11050 SO - Environ Health Perscectt 61:3-29 1901 LA - ENG A8 - Bioassays of vinyl chloride (VC 1 monomer were performed to assess the careinogenicity, types and locations of tumors induced, the effects of various modes of adm in i s tra t i on (particular',' those simulating potential human exoosure), and the level of risk. VC was administered to Sorague-Oawley rats, Wistar rats, Swiss mice, c c c c c 33 0 to CO CO o c c c L L 00005610 VINYL CHLORIDE PAGE 32 61 AU AO TI 51 SO LA AB 62 AU AU AO TI SI SO LA AB and golden hamsters. Methods of administration included inhalation (14 dose rates: 1-30.000 ppm, 4 hr/day, 5x/uk), ingestion (6 dose rates-' 0.03-50 mg/kg, 5x/wk for 52 wk), ip injection (4.25 mg lx or 2, 3. or 4x at 2-wk intervals), and sc injection (4.25 mg lx). VC was carcinogenic in all animal systems tested and was a multipotential carcinogen, causing various types of tumors at various sites. Some tumor types occurred in all species, while some occurred only in one species. Carcinogenesis was induced by inhalation, ingestion, and possibly injection. Response was strongly affected by duration and schedule of administration and strain and sex of the animals studied. VC was carcinogenic even at low doses and produced tumors in embryos after crossing the placenta. (13 Refs) Wyndar E L American Health Foundation, 320 East 43rd St., New York, NY, 10017 THE ETIOLOGY, EPIDEMIOLOGY, AMD PREVENTION OF LUNG CANCER. ICDB/82/10310 Semin Respir Med; 3(3):135-139 1962 ENG The risk of lung cancer increases proportionally with the number of cigarettes smoked/day and the number of yr smoked. Smoking is the primary cause of lung cancer. Epidemiologic studies have suggested that risk of lung cancer decreases with reductions in the amount of tar in cigarettes smoked. Occupational exposure to asbestos, uranium, arsenic, coal products, bischloromethyl ether, vinyl chloride, nickel, chromium, iron oxide, and mustard gas is also associated with an increased risk of lung cancer. Some occupational exposures work synergistically with tobacco smoke. The higher rate of lung cancer in cities than rural areas can be explained by higher frequency of smoking, more occupational exposure to carcinogens, and higher reporting of lung cancer. The relationship between passive inhalation of cigarette smoke and lung cancer is unproven. Lung cancer can be prevented by preventing smoking in children, the cessation of smoking by adults, and by developing less harmful cigarettes. (15 Refs) Filatova V5 ; Antoni uzhenko VA Smulevich VB ! Fedotova IV Kryzhanovskaia NA i Bochkareva TV ; Goriacheva LA I Bul'bulian MA Res. Inst. Industrial Hygiene and Occupational Diseases, Gorky, USSR CARCINOGENIC ACTIVITY OF VINYL CHLORIDE (DATA OF CLINICO-HYGIENIC AND EPIDEMIOLOGICAL STUDY). ICDB/62/10045 Gig Tr Prof Zabol ; <1):28-31 1902 RUS Incidence of malignant tumors was studied in workers who had an occupational exposure to vinyl chloride (VC) and polyvinyl chloride (PVC). Group 1 was exposed to VC at greater than 300 mg/cubic meter (m3). Group 2 was exposed to VC in concentratIons of 30-300 mg/m3, and Group 3 was exposed to VC in concentrations of less than 30 mg/m3. Analysis of cancer morbidity showed that 31.7/ had stomach cancer, 26.9/ had lung cancer and 14.3/ had 00005611 VINYL CHLORIDE PAGE 33 lymphatic and hematological malignancies. Cancer mortality index in Groups 1, 2, and 3 lias 1.4, 1.3, and 0.6, respectively. Cancer mortality depended upon the duration of exposure. (15 Refs) 63 AU AO ri si so LA AO International Cancer Research Data Bank National Cancer Institute International Csncer Research Data Bank, NCI, NIH, Westwood Bldg. 10A1S, 5333 Westbard Ave., Bethesda, t!D, C02Q5 THE CARCINOGENICITY OF VINYL CHLORIDE AND RELATED COMPOUNDS (ONCOLOGY OVERVIEW). 1003/60/76614 The Care inoqeni ci ty of Vinyl Chloride ar.d Related Compounds (Oncology Overvieu), Van Duuren BL, ed. This Title is Available Through National Technical Information Service, Springfield, Va, as P3S0-922904, 65 pp., 1980. ENG ONCOLOGY OVERVIEWS are retrospective bibliographies with abstracTs, published by the International Cancer Research Data Bank Program of the NCI. Each issue contains 100-500 selected abstracts on topics of high interest to cancer researchers, as well as an editorial commentary, subject and author indexes. This ONCOLOGY OVERVIEW cn The carcinogen IcI tv of vinyl chloride and related compounds contains selected abstracts of articles published mainly during 1975-79. It includes articles on the careinogenicity, teratogenicity, and mutagenicity of vinyl chloride and related compounds including chloroprene vinylidene chloride, tr i chloroe thy lane ar.d d i chloroe thylene , and other analogous halogenated hydrocarbons. Studies of the chemistry and analysis, pharmacokinotics , bioloaical effects in animals and humans, chemical structure and blolcqicai activity of vinyl chloride and its analogs are included. Also included are epidemiological investigations and discussions of public health issues, occupational safety and regulations. Studies of halcqenated aromatics and of anesthetics are specifically excluded from this OVERVIEW. 64 AU AO Tl SI SO LA AO Bergman K Toxicology Lab., Natl. Food Admin., Box 622, S-751 26 Uppsala, Sueden REACTIONS OF VINYL CHLORIDE WITH RNA AND DMA OF VARIOUS MOUSE TISSUES IN VIVO. ICDD/C2/0CO16 Arch Toxicol; 49(2)1117-129 1932 ENG The irreversible binding of 14C-vinyl chloride metabolites to RNA and DNA of mouse brain, lung, 1iver, kidrev, spleen, pancreas and testes after a single ip injection has been studied. Hydrol',sates of nucleic acids from selected organs were separated cn Aminex A6 for quantitation of alkylation products. Radioactivity in nucleic acids uas registered in all of the studied organs with The exceotlon of brain. RNA from spleen, pancreas and 1 iver, and DNA from spleen and 11ver contained the highest amounts of rad Ioac11viTy. In nucleic acids from spleen and pancreas , both organs of high metabolic activity, the entire 00005612 VINYL CHLORIDE PAGE 36 radioactivity Was found metabolically incorporated as Cl-fragments. In RNA of kidney and liver, a large part of the radi oac t i vi ty was also present as incorporated Cl-fragments , but 3,N4-ethenocytidine (in kidney) as well as 1,N6-ethenoadenosine and 1,N6-ethenoadenine (in kidney and liver) were identified as alkylation products. In liver DMA, inccrporation of Cl-fragments was insignificant, indicating different interactions of vinyl chloride metabolites (Cl-fragments and alkylating products ) uith RNA and DNA. The elution profiles of radioactivity in hydrolysates of liver DNA were dominated by an alkylation product of unknown structure (probably a derivative of deoxyguanosine). Possibly, 1,N6-ethenodeoxyadenosine and 1,N6-ethenoadenine were also present in liver DNA. The results are consistent with the ability of viny chloride to act as a multipotent carcinogen by alkylation of DNA in several tissues. (Author abstract) (45 Refs) 65 AU - Zimmerman HJ AD - George Washington Univ. Sch. M'dicine, Washington, DC TI - JAUNDICE: DRUGS THAT CAN CAUSE ICTERUS. SI - ICDB/S2/03723 SO - Consultant; 22(2 ):76-79,83-35,69 1932 LA - ENG A3 - Drug-induced jaundice which results from direct injury to hepatocytes is discussed. Such injury is reviewed with a discussion of mechanisms of action, effecting drugs according to therapeutic application, and treatment of drug-induced lesions. Many drugs used in oncotherapy produce steatosis, necrosis, or degeneration of cells or hepatocanalicular cholestasis. Benign liver cell adenoma, malignant hepatocellular carcinoma, and hepatic angiosarcoma are caused by such drugs as anabolic and contraceptive steroids, thorotrast, vinyl chloride, and inorganic arsenic. (3 Refs ) 66 AU - Clemmesen J AD - (c/o P. H. Lohman), Medical Biological Lab. TNO, P.O. Box 45, 2230 AA Rijswijk, The Netherlands TI - MUTAGENICITY AND TERATOGENICITY OF VINYL CHLORIDE MONOMER (VCM): EPIDEMIOLOGICAL EVIDENCE. SI - ICCB/32/0S603 SO - Nutat Pes; 93(1):97-100 1982 LA - ENG AB - While there is little evidence to attribute isolated cases of hepatic anqiosarcoma to to vinyl chloride monomer (VCM) exposure, it would be important if mutagenic or Teratogenic effects of VCM could be demonstrated in The surroundings of factories or in the domestic environment of workers. In support of this thesis, a review of epidemiological studies was made to find supportive evidence in the form of excess infant deaths or birth defects. Although excess birth defects were found in an Ohio study, These could not be attributed To polyvinyl chloride (PVC) plants due to the nonuniform distribution within communities having plants and those without them up To 12 miles awav. Although excess CNS-malformation in newborns was found in another study, in cne 00005613 VINYL CHLORIDE PAGE 35 of The towns with two PVC plants> none of the parents of involved patients worked at the plants. An attempt to determine infant death rates from pregnancies initiated before and after exposure of the same fathers to VCM or PVC fabrication have been confused by a number of factors. It was concluded that none of these studies were supportive of VCM or PVC plants being responsible for isolated hepatic anqiosarcoma. excess Infant death rates, or excess birth defects. (8 Refs) 67 AU - Bolt HM ) La i b RJ Filser JG AD - Pharmakoloqisches Institut, Abteilung Toxikologie, Johannes Gutenberg-Universitat Mainz, Obere Zahlbacher Strasse 67, D-6500 Nainz, W. Germany TI - REACTIVE METABOLITES AND CARCINOGENICITY OF HALOGENATED ETHYLENES. SI - ICD5/82/06816 SO - Blochem Pharmacol; 31(l):l-6 1932 LA - ENG A8 - Mutagenicity and careinogenicity of halogenated ethylenes (HE) are reviewed with special emphasis on the role of molecular rearrangement in metabolic detoxlcation. Comparison of the data on the formation of hepatic preneepiastic foci after exposure of young Ulster rats to HE with the metabolic data showed significant reduction of the wide range of oncogenic activities when the prenooplastic effects were related to the amount of HE metabolites produced after 600 hr of exposure. It is suggested that monochlorooxirane (the epoxide of vinyl chloride) represents an optimum between stability and reactivity to reach the DNA target and react with it. (67 Refs) 68 AU AD TI SI SO LA AB " Popper H ; Selikoff IJ - Stratton Lab., Mount Sinai Sch. Medicine, City Univ. New York, 10 East 102nd St., New York, NY, 10029 - CLASSICAL SYNDROMES IN OCCUPATIONAL MEDICINE: PATHOLOGICAL LESSONS FROM VINYL CHLORIDE ANGIOSARCOMA. - ICD3/82/0S810 " Am J Industr Med; 2(2)1187-196 1931 ENG Similarities in the evolution of the various staqes of vinyl chloride (VC)-induced hepatic lesions in man and experimental animals are discussed. The initial lesion in man and rodents is focal proliferation of hepatocytcs which show variations in size and appearance of nuclei. Increase of perisinusoidal collagen fibrils and of fat-storing interstitial Cells, precursors of fibroblasts, is present. Silver lmpreqnation visualizes The increase of reticulm fibers In cIrcumscrI bed zones. The precursor lesions do not exclude the simultaneous presence of fully developed angiosarcoma (AG) in other parts of Use liver. Diagnostic follow-uo by radionuclide scanning, angiography, and subsequent confirmation b\' open liver biopsy are indicated. The pro 11feration of sinusoidal cells becomes more conspicuous in both man and animals, and cells with hyperchromatic splndle-snaped nuclei gradually exceed the other sinusoidal cells in number. Intralobular AS is always multicentric In rodents. 00005614 VINYL CHLCPIDE PAGE 36 69 AU AD TI SI SO LA A8 70 AU AO TI SI SO LA AO Exposure of newborn rats produced mainly hepatocellular carcinoma. Trabecular AS is The more frequent form. Increased connective Tissue and AS cells which invade the cords are present leading To atrophy and disappearance of hepatocytes. Solid nodules of AS often form. In humans all forms of AS are almost aluays multicentric discouraging surgical intervention even at early stages. VC produces a well defined histological sequence in animals and man>leading to control of exposure and avoidance of additional disease. (36 Refs) Brenner EA i Manchester KL ; Uebster I ; Cantrell AC National Centre for Occupational Health. P.0, 4703. Johannesburg, South Africa ATTEMPTS TO DEMONSTRATE SHORT-TERM METABOLIC EFFECTS OF VINYL CHLORIDE IN NORMAL RAT LIVER. ICOB/82/03506 Am J Industr Med! 2(2)1153-159 1981 ENG Effects of "inyl chloride monomer (VCM) and one of The metabolites, chloroacetaldehyde, on cell metabolism were assessed measuring adenine nucleotide concentrations and resting transmembrane potentials. Results indicated that VCM does not alter general cell metabolism but could act on specific intracellular target. (16 Refs) Supuki Y Environmental Sciences Lab.. Mount Sinai Sch. Medicine, One Gustav Levy Place, New York, NY, 10029 ELECTRON MICROSCOPIC OBSERVATIONS OF HEPATIC AND SUBCUTANEOUS HENANSIOSARCCNAS INDUCED IN MICE EXPOSED TO VINYL CHLORIDE MCMQMCR. IC03/32/08804 Am J Industr Med) 2(2)1103-117 1931 ENG Neoplastic effects of vinyl chloride was studied in mice in short exposure (4 uk ) to low doses (1, 10, 100, 300, and 600 ppm). A mouse of the 10 ppm group developed a subcutaneous hemangiosarcoma, 29 wk after exposure. Histologically the tumor was localised in the subcutaneous connective tissue of the ear, and formed blood channels that appeared to be freely communicated. Neoplastic cells (NC) That directlv lined The blood cavities were generally attenuated. Focal necrosis, hemorrhage, and hemosiderin deposition were observed. U1trastructure of Tne attenuated NC was similar to That of capillary endothelium in the connective Tissue, A mouse of The 600 opm group developed an hepatic hemangiosarcoma approx 65 wk after exposure. The tumor was found on the surface of The lobe of the liver, and in addition, multiple pulmonary Tumors were observed. The hepatic Tumor showed formation of cystic blood channels, and the stroma of the Tumor was freouentlv sclerotic. Neoplastic tissue contained degenerated hepatic parenchyma. NC lining the blood cavity were attenuated compared with normal sinusoidal endothelium. PericyTe-11ke cells were character1 zed by The 00005615 VINYL CHLORIDE PAGE 37 presence of pinocylotic vesicles end dense bodies beneath the cell membrane. Under normal conditions the pericyte does not exist in Disse's space of the mouse. Alveolcgenie tumors were induced at high rate in mice 12 wk and longer after exposure; 23/24 mice in the 600 ppm group, 12/19 in the 300 ppm, 7/16 in the 100 ppm, 3/20 in the 10 ppm group, and in 2/33 control group. (28 Refs ) 71 AU - Sal'nikova LS ; Vorontsov RS AO - Inst. Industrial Hygiene and Occupational Diseases, Moscow, USSR TI - LONG-TERM EFFECTS OF VINYL CHLORIDE ON EM3RY0GENESIS. SI - ICDB/62/C8416 SO - Gig Tr Prof Zabol; (12) =56 1931 LA - RUS A3 - Potential transplacental carcinogenic effect of vinyl chloride (VC) was studied in SHK mice. Pregnant females were subjected to inhalation exposure to VC at 35.3 and 4.3 mg/cubic meter. The offspring were followed up for 1-1.5 yr. The antenatal exposure to VC did not increase the incidence of malignant tumors. (6 Refs) 72 AU - Emmerich KH i Norpoth K AO - Ir.s T . Pathology, Uniu. Munster, Oomag'Ls tr. 17, D-4400 Munster, W. Germany TI - MALIGNANT TUMORS AFTER CHRONIC EXPOSURE TO VINYL CHLORIDE. SI - ICDB/32/05131 SO - J Cancer Res Clin Oncol; 102(1): 1-11 1931 LA - ENG AS - Correlations between exposure to vinyl chloride and the development of malignant tumors in the liver have been known since 1974 and have been confirmed by many an experimental investigation. Based on the evaluation of mortality statistics from nine different countries an increased incidence of malignant Tumors of the lung, the gas frolntestinal tract, and The central nervous svstem (CMS), and of malignant lymphomas is documented in connection with exposure to vinyl chloride. Statistically significant increases, however, are only found in the incidence of malignant liver Tumors. Metabolism and toxicology of vinyl chloride are discussed in detail. (Author abstract) (73 Refs) 73 AU - von Danlken A ; Friederlch U ; Lute UK J Schlatter C AO - Inst. Toxicology, Swiss Federal Inst, Technology, CH-S603 Schuerzenbach, SwiTzerland TI - TESTS FOR MUTAGENICITY IN SALMONELLA AND COVALENT BINDING TO OKA AND rPOTEIM IN THE PAT OF THE PIOI CONTROL AGENT 0-CHL0RC3ENZYLIQEMS NALONONITRILE (CS). SI ICDB/82/04753 SO Arch Toxicol; 49(l):i5-27 1901 LA ENG AB The aim of This study was To determine whether o-chlorobengy11 dene aioronitrIle (CS) exhibits any genotoxic activity towards Salmonella or mammalian DMA in vivo. CS was synthesized with a (140 -label at The benzylle carbon aton. It was adm i n l s tered Ip ar a dose le-'el of 13 mg/kq (1 mCi/kg) to 00005616 VINYL CHLORIDE PAGE 38 young adult male rats. Liven and kidney DNA was isolated after 8, 5i and 75 hr. The radioactivity was at (liver* 8 and 75 hr) or belou (all other samples) the limit of detection of 3 dpm. Thereforei a possible binding of CS to DNA is at least 10(5) times lower than that of the strong hepatocarcinogen aflatoxin Bli and 6>000x lower Than that of vinyl chloride. In contrast to this lack of ONA binding, but in agreement with The chemical reactivity of CS, a binding to nuclear proteins could be detected with specific activities ranging between 50 and 121 dpm/mg for liver and between 3 and 61 dpm/mg for kidney. Protein binding could Well be responsible for its pronounced cytotoxic effects. CS was also tested in the Ames Salmcnelia/microsome assay. Strains TA 1535, TA 1537, TA 1533, TA 90. and TA 100 were used with or without pre-incubation, Only with strain TA 100 and only without pre-lncubation, a doubling of the number of revertants was detectable at the highest dose levels used, 1,000 and 2.000 ug CS per plate. With pre-incubation of TA 100 with CS, a slight increase of the number of revertants wa3 seen at 100 and 500 ug per plate, and a subsequent fall belpw control values at 1,000 ug. A check for the number- of surviving bacteria revealed a strong bacteriotoxiciTy of the higher doses of CS so that the calculated mutation frequencies, le, the number of revertants per number of surviving bacteria, increased with doses up to 500 ug. This toxicity could be counteracted in part by the addition of increasing amounts of rat liver mlcrosomes. In the view of These results, and taking into account the rare and low exposure of man, it is concluded that CS will not create a risk for the induction of point mutations or of carcinogenic processes mediated by DNA binding. (Author abstracT) (26 Refs) 76 AU - Franc T!C ! Meunier A ! Catillna P AD - No affiliation given TI - MUTAGENIC, TERATOGENIC OR TOXIC SUBSTANCES IN THE PREGNANT WOMAN WHICH MAT BE ENCOUNTERED IN THE WORKING ENVIRONMENT. SI - ICOB/82/06563 SO - Arch Mai Prof M'd Trav Secur Soc ! 62(3K183-196 1931 LA - FRE AD - Chemical and physical mutagenic and Teratogenic agents and toxic substances to which pregnant women can be exposed In the working environment are reviewed. The occupational mutagens include benoene, benco(a Ipyrene, vinyl chloride and aflatoxins. Exposure of experimental animals to carcinogens durinq pregnancy caused increased tumor frequency in the first Three generations, (196 Refs ) 75 AU - losquin CJ AD - Catedra de Medicina Interna A, Facultad de Ciencas Medicas, La Plata, Argentina TI - PRIMARY HEPATIC CARCINOMA. SI - ICCB/e2/03752 SO - Pev Fac Cienc Plata! 6(2):27-31 1981 LA - SPA AB - Primary hepatic carcinoma (PHC) was reviewed. The following 00005617 VINYL CHLORIDE PAGE 39 topics were discussed: etiology (cirrhosisi food, infections, parasites, hormones, ThorotrasT, As. and vinyl chloride), pathologic anatomy (tumors derived from the parenchyma or the mesenchyme), diagnosis (clinical, biological, and morphological), and treatment. (61 Refs) 76 AU - ttohrmann W AD - Klinik fur Berufskrankheiten, Muncher Allee 10, 0-8230 Bad Reichenhall, W. Germany TI - ULTRASOUND DIAGNOSIS WITH EXAMPLES OF USE FROM OCCUPATIONAL ME0ICINE. SI - ICD3/82/0320B SO - Zentralbl Arbeitsmed Arbeitsschutz Froph! 31(101:398-601 1981 LA - GER AB - Properties of ultrasound (US) and applications of US diagnosis in occupational medicine are described. U5 employs frequencies of 1-10 megahertz and detects acoustic differences in structure, such as between solid tissue and fluid. US is used in occupational medicine to detect conditions such as disease induced by vinyl chloride, and mesothelioma, (no Refs) 77 AU - Beaumont JJ ; Breslow NE AD - Industrywide Studies Branch F-8, Natl. Inst. Occupational Safety and Health, 6676 Columbia Parkway, Cincinnati. CH, 65226 TI - FOWER CONSIDERATIONS IN EPIDEMIOLOGIC STUDIES OF VINYL CHLORIDE WORKERS. SI - ICD3/82/0U36 SO - Am J Epidemiol) 116(51:725-736 1901 LA ENG AB Nine retrospective mortality studies of workers exposed to vinyl chloride were reviewed to determine whether differences in their hypothesis testing results might be due to differences in statistical power. Where possible, the power of each study was calculated for cancer of the iunq, brain and liver. When power was taken into consideration, the results for liver and brain cancer were found to be consistent with an ctlologlc role for vinyl chloride. For lung cancer, the data were not consistent with an etiologic role, in that two studies with very high power yielded negative results. (Author abstract) (16 Refs) 70 AU AD TI SI SO LA AB Anderson 0 J Richardson CR British Industrial Biological Res. Assoc., Woodmansterne Road, Carshalton, Surrey SMS AOS, England ISSUES RELEVANT TO THE ASSESSMENT OF CHEMICALLY INDUCED CHROMOSOME DAMAGE IN VIVO AND THEIR RELATIONSHIP TO CHEMICAL MUTAGENESIS. ICOB/31/33319 Mutat Res! 90(31:261-272 1981 ENG Male Wistar rats were killed 6 or 26 hr after sinqle or multiple exposure to clastogens, and bone marrow samples were prepared. Benzene, mitomycin C (MltC), ethyl methane sulfonate (EMS), trlmethyl phosphate (TMP), and vinyl chloride (VC) constituted 000056X3 VINYL CHLORIDE PAGE 40 the groups of elasTogens analyzed. A statistically significant increase in percentage of abnormal cells above negative control values i as uell as some increases in individual categories of chromosome damage ware observed after treatment with each clastogan. Dose-response relationships were evident for benzene, EM5, and HiTC. For TMP and VC only one dose level was tested. Gap incidence increased above that of other types of chromosome damage. Multiple exposure at the same sampling time and with the same route of administration produced similar or smaller total amounts of chromosome damage than single exposure. Higher yields of damage were obtained at 6 hr than at 24 hr after treatment with benzene. Benzene also produced a similar level of damage after ip injection or a single Z hr exposure bv inhalation. (13 Pef3 ) 79 AU - Guengerich FP ; Geiger LE t Hogy (_L I Wright PL AO - Dept. Biochemistry and Center in Environmental Toxicology, Vanderbilt Univ. Sch. Medicine, Nashville, TN, 37232 TI - IN VITRO META30LI5M OF ACRYLONITRILE TO 2-CYANOETHYLENE OXIDE, REACTION WITH GLUTATHIONE, AND IRREVERSIBLE BINDING TO FR0TEIM5 AND NUCLEIC ACIDS. SI - ICDS/81/32562 SO - Cancer Res! 41(121:4925-4933 1931 LA - ENG AB - The metabolism of the suspected carcinogen acrylonitrile was studied using subcellular fractions isolated from rats and humans. Irreversible binding of radioactive label from C1-14CJor [2,3-140acrylonitrlla to protein and DMA was enhanced by reduced nicotinamide adenine dinucleotide phosphate in the presence of rat liver microsomes or a reconstituted cytochrome P-450 system. During the reduced nicotinamide adenine dlnuoleotide phosphate-dependent reaction, HCH was produced, and the heme of cytochrome P-450 was destros'ed. Rat brain microsomes did not produce detectable levels of metabolites. Conclusive evidence of metnbolIcally mediated binding of acrylonitrile to protein and ONA in human systems was not found. With rats, metabolism was induced by pratreatment of animals with either phenobarb i tai or 5,6-benzof lal,one . Labeled -cyanoe thy lens oxide was found to bind irreversibiy to calf thymus ONA and microsomal protein. The extent of binding was greater in the case of 2,3-14C-labeled than l-14C-labe!ed material. The relative first-order rata of acrylonitrile binding to calf thymus ONA in rat liv^r microsomal systems was one To two orders of magnitude less Than That for 1,1,2-Trichloroethylene and three orders of magnitude less than that for vinyl chloride or vinyl bromide. Rat liver microsomes or a reconstituted cytochrome P-450 systei catalyzed the mixed-function oxidation of acrylonitrIle to 2-cyanoethylene oxide. 2-Cyanoethylene oxide has a half-life of about Z hr in neutral buffer at 37 C. This epoxide was found To serve as a substrate for microsomal eooxide hydrolase. HCN was released during hydrolysis of 2-cyanoeThy1ene oxide or reaction of The epoxide with reduced glutathione", however, HCN release in either case was not stoichiometric with epoxide disappearance. 00005619 VINYL CHLORIDE PAGE 41 80 AU AD TI SI SO LA AB 81 AU AD TI 51 SO LA AO 2-Cyanoethylene oxide reacted less rapidly with reduced glutathione than did aerylonitrila. Rat liver cytosol preparations contained glutathione S-transferasa activity towards aerylonitrile and greater activity with Z-cyanoethylene oxide as a substrate. Cytosol preparations from rat brain and human liver had no detectable glutathione S-transferase activity towards aerylonitrile but did exhibit some activity towards 2~cyanoetnylene oxide. These studies establish the basic pathways involved in the metabolism of aeryIonitrile and should provide a basis for examination of the relevance of these individual steps and their roles in bioactivation and detoxication under more physiological situations. (Author abstract) (40 Refs) Theriault G ; Allard P Dept. Social and Preventive Medicine. Sch. Medicine. Laval Univ,. Ste-Fov. Quebec. Canada CANCER MORTALITY OF A GROUP OF CANADIAN WORKERS EXPOSED TO VINYL CHLORIDE MONOMER. IC0B/81/31040 JOM; 23(10):671-676 1981 ENG The present study was undertaken to find out whether there was an excess of cancer mortality from causes other than angiosarcoma of the 1iver among a grouo of workers heavily exposed to vinyl chloride monomer (VCM). The mortality of 451 workers exposed to VCM for more than 5 yr was compared with that of 870 workers from the same company who had not been exposed to VCM. The relative risk for digestive cancer was significantly higher than 1 (6.25. confidence interval 2.69 to 14.52) in the exposed group. The standardised mortality ratio (SNR) for digestive cancer was also higher (SNR 259.26 p less than 0.01) than that of the general population. No other cancer was in excess. Since the exposed workers are known to have had a cigarette smoking experience similar to that of those who ware not exposed, it is concluded that the association between lung cancer and VCM exposure, if present, is indeed rather small. (Author abstract) (25 Refs) Guengerich FP ; Mason PS i Stott WT ; Fox TR I Watanabe PG Dept. Biochemistry, Center Env l r oilmen tal Toxicology, Vanderbilt Univ. Sch, Medicine, Nashville, TN, 37232 ROLES OF 2-HALOETHYLENE OXIDES AND 2-MALOACETALDEHYDES DERIVED FROM VINYL EROMIDE AND VINYL CHLORIDE IN IRREVERSIBLE BINDING TO PROTEIN AND ONA. ICDB/B1/30770 Cancer Res) 41( II ,partl ) -'4391-4398 1981 ENG The metabolism of Cl, 2-14C)viny1 bromide (VCR) to products Irreversibly bound To DMA and protein was examined in rat liver mlcrosomes, reconstituted eytocr.ra.ne P-450 systems, and isolated heoatocytes. A role for eytochrcie P-450 was confirmed uslrg inhibition and reccns11 tution experiments. The major form of cytochrome P-450 involved in V3R metabolism does not appear To be either of The major isocymes induced by phenobarbital or 00005620 VINYL CHLORIDE PAGE 42 beta-naphthoflevonei as determined by inductioni reconstitution> and antibody inhibition studies. 2-Bromoethylene oxide and 2-bromoacetaldehyde> suspected metabolites of VBR, were synthesized and found to be substrates for rat liver epoxide hydrolase and equine 1iver alcohol dehydrogenase, respectively. These enzymes were used to probe the roles of the Two possible metabolites in the irreversible binding of products of VBR to protein and DNA. Alcohol dehydrogenase was more effective than epoxide hydrolase in inhibiting the binding of VER metabolites to protein in microsomal incubations. Epoxide hydrolase was effective in inhibiting the binding of VBR or vinyl chloride metabolites to calf thymus DMA added to such systems* but alcohol dehydrogenase was not. Similar results were obtained for binding of VBR metabolites to DNA in a reconstituted enzyme system. Reduced glutathione blocked nonenzymatic binding of 2-bromoCl.2-140acetaldehyde to protein but not DNA. Binding of vinyl chloride and VBR metabolites to protein was blocked by reduced glutathione, but binding to DMA was not. These results are consistent with the view that 2-naloethylene oxides are the major alkylating agents bound to DNA. and 2-haloacetaldenydes are the major alkylating agents bound to proein in these experimental systems. Studies with labeled 2-brcmoacetaldehyde indicate that the slow kinetics of DNA binding by this compound is responsible in part for this phenomenon. Studies with isolated rat hepatocytes suggest that a significant portion of the total and reactive metabolites are able to leave these cells. In these systems, binding of metabolites of vinyl chloride to DNA outside the hepatocytes could be partially blocked by epoxide hydrolase or by alcohol dehydrogenase, implying that, as targets farther away from sources of reactive species are considered, the stabilities of these species become more important for reaction with nucleophilic sites, (Author abstract) (36 Refs) 62 AU - Konetzke GW AD - Zentralinstitut fur ArbeitsmedIzin der DDR, Noldnerstrasse 40-42, 1134 Berlin, E, Germany TI - CCCUPATIOfJAL CANCER: PROBLEMS AND TASKS OF MEDICAL PRACTICE. SI - ICD0/01/30709 SO - Z Aerztl Fortbild (Jena); 75(11/121:529-531 1901 LA - GER AB - The problems of occupational cancer and its prevention are discussed. Aside from ionizing radiation, asbestos and chemical substances are the most Important carclnoqanic factors in (he working environment. The number of industrial chemicals with demonstrated or probable carcinogenic effect is only 30-40. They include am I nodi phenyl, arsenic, asbestos, auramines, benzene, benzidine, technical chloromethylmethylethen, chromium, , 2-dl chlorodi e thy 1 sulfide, di e-hlorodi me thy le ther , beta-naphthylam 1ne , nickel, tars, mineral oils, and vinyl chloride. Afiatoxlns, aeryIoni *rIle , beryllium, poiychlorinaTed biphenyls, cadmium, d I me t hy icarbony lc'nl or 1 de > d l me Thy lsul f a T e , ethyl oxide, and carbon Tetrachicrlde are probable carctrogens. Occupational exposure to asbestos was definitely established in 00005621 VINYL CHLORIDE PAGE 43 63 AU AD TI SI SO LA A3 64 AU AD TI SI SO LA AB 303/743 patients with malignant mesothelioma, and occupational exposure uas probable in 70. The prevention of occupational cancer includes the limitation of the use and production of carcinogenic substance to the extent absolutely necessary technologically, ban on especially hazardous carcinogens, comoiiance uith occupational safety measures and hygienic standards, and checK-Up and monitoring of workers who have ever been exposed to carcinogenic factors. (7 Refs) Spit BJ ; Feron VJ ; Handriksen CF Institute CIVO-Toxicology and Nutrition TNO, P.O. Box 360, 3700 AJ Zeist, The Netherlands ULTRASTRUCTURE OF HEPATIC ANGIOSARCOMA IN RATS INDUCED BY VINYL CHLORIDE. ICD3/61/29974 Exp Mol Pathol; 35(21:277-204 1931 ENG The hepatic angiosarcoma studied uas from a male Wistar rat having been exposed to vinyl chloride monomer (VCM) by the oral route for 120 wk. Widened sinusoids lined bv large electron-lucent, spindle-shaped tumor cells and membrane-bound nucleai--free structures were seen in the transitional zone between the tumor mass and the adjacent liver tissue. In areas merely consisting of tumor tissue the tumor cells had a more angular or irregular shape. The origin of the tumor cells is discussed in light of the characteristic differences between endothelial cells and Kupffer cells described in the literature. Although an endothelial origin of the tumor cells could not be established unequivocally, it uas concluded that at present there is little reason to doubt such an crlqln. (Author abstract) (21 Refs ) McDonald JC ; Harrington JM TUC Centenary Inst. Occupational Health, London Sch, Hygiene and Trooical Medicine, London WCIE 7HT, Enqland EARLY DETECTION OF OCCUPATIONAL HAZARDS. ICDD/81/29061 J Soc Occup Med; 31<3):93-98 1981 ENG Because of the rate of technological change, the time interval between exposure to a hazard and the appearance of its effects may be ''Ary long. Surveillance procedures for occupat i onal ly related diseases and injuries in Britain are generally regarded as inadequate. Reported intervals between the first suspicion and general acceptance of some occupational hazards have varied from 2 to 59 yr (for angiosarcoma due to vinyl chloride monomer and bladder cancer due to aromatic amines, respectively). Some occupational diseases have only been recoqniqed by chance, having been completely missed by existing methods of reporting or the discovery uas not reported. Detection of occupational hazards has frequently depended upon astute clinical observation; a system of reoid informal communication about such 'hunches' Is needed. There are parallels for this idea in the history of determining 'y^. i?; v -' c 00005622 VINYL CHLORIDE 3J 0) O) (0 o to 03 PAGE 44 c the etiology of numerous communicable diseases. The essentially informal reporting networks for communicable diseases operating c in Britain and the United States are linked to central analysis units which can initiate rapid field studies when indicated. The establishment of an analogous system for occupational disease is advocated, (no Refs ) 35 AU - Dabney BJ AD - IBM Corporation, P.0. Box 1900, Boulder, CO, 60302 TI - THE ROLE OF HUNAN GENETIC MONITORING IN THE WORKPLACE. SI - ICD3/31/27915 50 - JOM; 23(9):626-631 1961 LA - ENG A3 - The history and current state of some newer short-term tests for occupational genetic monitoring are reviewed. These are: cytogenetics, sister chromatid exchange, body fluid analysis, tests utilising sperm, and detection of somatic cell variants. Occupaticnal studies on benzene, vinyl chloride monomer, and epichlorohydrin are critically discussed from the standpoints of design and interpretation. It is concluded that these tests are net appropriate for risk assessment at the present time. Their clinical relevance, if any, is unknown. Proper validation and standardization have not been done, and design problems have often clouded the results of previous studies. There is a critical need for further research in the area of occupational genetic monitoring. Future aoplications should include L integration with prospective morbidity and mortality studies, standardization of design and statistical methods, and development of new tests with genetically relevant endpoints. (Author abstract) (44 Refs) 66 AU - Rodnan GP AD - Div. Rheumatoloqy and Clinical Immunology, Dept. Medicine, Univ. Pittsburgh, Pittsburgh, PA, 15261 TI - WHEN IS SCLERODERMA NOT SCLERODERMA? THE DIFFERENTIAL DIAGNOSIS OF PROGRESSIVE SYSTEMIC SCLEROSIS. 51 - IC03/01/27247 SO - Bull Rheum Dis) 31f 2):7-10 1931 LA - ENG (.. AB - Cutaneous plaques or nodules resemblinq those of progressive systemic sclerosis (P5S; systemic scleroderma) may develop in workers exposed to vinyl chloride or frIchloroethvlene. Chemotherapy which bleomycin often causes PSS-like fibrosis, which subsides when the agent is discontinued. 5everal disorders, including the carcinoid syndrome and myeloma-associated amyloidosis, may be character 1 zed by PSS-like skin thickening. Differential diagnosis is usually not difficult, because the visceral components of PSS are absent and/or the characterlstic clinical features of the underlying disease are present. (20 Refs 00005623 VINYL CHLORIDE PAGE 45 87 AU - Sslikoff ij AO - Environmental Science Lab., Oept. Community Medicine, Mount Sinai Sch. Medicine, city Univ, New York, Hew York, NY, 10029 TI - CARCINOGENIC RISK MANAGEMENT IN THE UNITED STATES. SI - ICD3/81/26715 SO - Ann NY Acad Sci; 363:283-293 1981 LA - ENG AB - Carcinogenic risk management is in the developmental stage in the United States. Data from studies of smoking, asbestos, and vinyl chloride hawe shown the effect of carcinogen dose on the incidence and development of cancers. As a result, the ves-or-no approach to carcinogens has been replaced by regulation based on the dose-response approach. Observation and regulation of carcinogens is being extended from the Workers who produce them to include anyone who is exposed during the life of the carcinogens. Other aspects under study include latency, absence of thresholds, dose-induetion periods, and multiple factor interactions. The extrapolation of animal data to man remains a debated subject. Observations indicate that, with at least some carcinogens, risk is reduced in time if exposure to the carcinogen ceases. The relationship between mutagenicity and careinogenicity is still uncertain. The reproductive effects of carcinogens and the decision to ban or control them present ethical and legal questions that remain unanswered. (15 Refs) 63 AU AO TI SI SO LA AB - Preuss PN - Health Sciences, United States Consumer Product Safety Commission, Washington, DC - THE ELIMINATION OF CARCINOGENIC RISKS IN CONSUMER PRODUCTS. - ICDB/G1/26 704 - Ann NY Acad Sci) 363:63-73 1981 - ENG - Statutes of the Consumer Product Safety Commission (CPSC) designed to assure that marketed products do not cause injury or illness are reviewed. Regulatory techniques include dissemination of product information to the media and consumers, labeling of consumer products, establishing performance or other standards, and banning certain consumer products. Os six occasions In its 8 yr of existence, the CPSC has determined that the products contain materials which present a risk of human cancer. Each of the six regulatory actions were unique. The products involved included >'inyl chloride, asbestos tr i s (hydro,<yme thy 1 lam 1 nome thane (TRI5), and bengene. Problems associated with balancing the risks, costs, and benefits are reviewed. An appendix containing The CPSC proposed methodology for commission conslderat1 on of findings under section 9(c) of the Consumer Product Safety IS c e c ( c (. c ./ 3D CO w (O o ro CJ1 00005624 VINYL CHLORIDE PAGE 46 89 AU - Anderson D ; Richardson CR ; Purchase IF ! Evans HJ ! O'Riordan ML AD - Central Toxicology Lab. , Imparl al Chemical Industries, Ltd., Aiderley Park, Macclesfield, Cheshire SXIO 4TJ, England TI - CHROMOSOMAL ANALYSIS IN VINYL CHLORIDE EXPOSEO WORKERS: COMPARISON OF THE STANDARD TECHNIQUE WITH THE SISTER-CHROMATID EXCHANGE TECHNIQUE. SI - ICDB/31/26470 50 - MutaT Res; 83(11:137-144 1901 LA - ENG A3 - Twenty-one workers exposed to vinyl chloride (VC) and six controls were subjected to consentional chromosomal analysis (CA) and the determine.! i on of sis tar-chromatid exchanges (SCE). In addition, SCE in human lymphocytes were studied before and after exposure to gaseous VC in vitro. These workers had been subjected to studies 13 mo before. In the exposed workers the av of the different types of abnormalities were significantly increased with CA, while only a slight, nonsignificant, increase of SCE was noted in the exposed group compared with the controls. In lymphocyte cultures exposed to VC during GO/early Gl, and late Gl/early S phase, no increase in SCE was noted without metabolic activation; a marked decrease was noted with activation and this was independent of cell cycle phase. The small increases of SCE m workers were attributed to low exposures rather than the inability of VC to induce SCE in human lymphocytes! the SCE levels could have returned to normal relatively quickly after exposure. It is suggested that SCE analysis might not be of much value after very low chronic chemical exposures, but might be useful during high chronic chemical exposures and during the first few days after acute exposure, (19 Refs) 90 AU - Vi anna NJ ; Brads' JA ; Cardnmone AT AD - Bureau Environmental Epidemioloav and Occupational Health, Albany, New York State Dept. Health, NY TI - EPIDEMIOLOGY OF ANGIOSARCOMA OF LIVER IN NEW YORK STATE. 51 - ICD3/01/25590 SO - NY state J Med; 81(6j:895-899 1931 LA - ENG A3 - The geographic distribution of angiosarcoma of the liver (ASL) among residents of New York was examined with special emphasis on the epidemiologic charactoristics which might be of etiologic importance in this malignancy. The av annual incidence rate for the state, excluding New York Cits', was 0.26 per million population. Of the chemicals associated with ASL, potential exposure to vinyl chloride appeared to be the most important factor in certain urban indue rialired counties, whereas probable arsenic exposure was the ma]o: -acto- in rural areas. Prior thorium dioxide injections ac: ounted for onlv 7/. of the 4J patients studied. We suggest ' hat certain chemicals structurally similar To vinyl chloride might be of etiologic importance anong patients who have no documented exposure to any of the established causes of ASL. (Author abstract) (25 Refs) x'-v.'--' //>;,/ cn 00005625 VINYL CHLORIDE 33 fi" (D 03 to Oro CD PAGE A7 cc 91 AU - Duverger M ; Lambotte M i Haivoisin ; De Haester C ; Ponceiet F AU - Marcier M A0 - (c/o Ponceiet) Lab. Biotoxicology, D.siv. Louvain Sch, Pharmacy, U.C.L.-73,69i B. 1200 Brussels. Belgium TI - META30LIC ACTIVATION AND MUTACENICITY OF A VINYLIC MONOMERS c (VINYL CHLORIDE, STYRENE, ACRYLONITRILE, BUTADIENE). SI - ICOB/81/2550A 50 - Toxicol Eur Res) 3(3):131-1AQ 1931 LA - ENG c AB - Literature data on the mutagenic activity and metabolism of monomers vinyl chloride (VCMJ, styrene (STY), acrylonitrila (ACN) and butadiene (BUT) are reviewed. Vinylic monomers were shown to be susceptible to metabolic conversion by the mixed function c oxidase of the endoplasmic reticulum into primary reactive intermediates (oxiranes). VCM, STY, ACN, and BUT uere mutagenic in Salmonella typhimurium test system. VCM was shown to induce recessive lethals in Drosophila melanogaster. Incubation of c Chinese hamster cells with VCM produced a dose-dependent mutagenicity and cytotoxicity. An increased frequency of chromosome aberrations was recorded in workers who had an occupational exposure to VCM and STY. (130 Refs) c 92 AU - Hong CB ; Winston JM ; Thornburg LP I Lee CC I Woods JS AO - (c/o Woods) Bat telle Seattle Res. Center, A000 N.E. Alst St., Seattle, UA, 93105 TI - FOLLOW-UP STUDY ON THE CARCINOGENICITY OF VINYL CHLORIDE AND VINYLIDENE CHLORIDE IN RATS AND MICE: TUMOR INCIDENCE AND MORTALITY SUBSEQUENT TO EXPOSURE. 51 - ICD3/S1/25A72 SO - J Toxicol Environ Health; 7(6):909-92A 1931 LA - ENG AB - The development and incidence of neoplastic changes and other effects during a 12-mo exposure follow-up period in male and female albino CD-I mice and CO rats exposed to vinyl chloride (VC) or uinylidene chloride (VDC) for various lengths of time were evaluated. Eight to 23 mice of each sex and A-16 rats of each sex were exposed to 50, 250, or 1,000 ppm VC, 55 ppm VDC, or filtered air for 6 hr/day, 5 days/tik. Exposure of mice and rats to VC for 1, 3, and 6 mo and 1, 3, 6, and 10 mo, respectively, increased the number of deaths and increased moribundity at all dose levels during the exposure and postexposure periods. The cumulative tumor incidence for essentially ail organ sites in animals exposed to 50 ppm VC or 55 ppm VDC was Similar to that in controls (except for mammary qland Tumors in female mice). Oily at higher dose levels of VC did significant increases in cumulative tumor Incidence occur. Cumulative tumor incidence durlnq the period after VC exposure increased with duration of exposure, independent of dose level. The implication of the findings with respect To the assessment of cancer risk resulting from exposure of humans to VC and perhaps other carcinogens is discussed. (23 Refs) c c c (_ L L  ;.. ;x c 00005626 VINYL CHLORIDE PAGE AS 93 AU Feron VJ ; Hendriksen CF ; Speek AJ ; Til HP ! Spit BJ c AD Inst. CIVO - Toxicology and Nutrition TNO, PO Box 360i 3700 AJi Zelst, The Netherlands TI LIFESPAN ORAL TOXICITY STUOT OF VINYL CHLORIDE IN RATS. SI ICDB/31/23949 c SO Food Cosinet Toxicol; 19(31:317-333 1931 LA ENG ci AB Vinyl chloride monomer (VCM) was administered to five groups each of 60-00 male or 60-80 female Wistar rats by incorporating polyvinyl chloride (PVC1 containing the VCM into the diet or by gastric intubation of 10/ VCI1 soln in soya-bean oil. The actual exposures To the VCM provided by the PVC were 0 (controlli 1.7 5.0, and 14.1 mg/kg body wt/day, and that provided by the VCM c soln was 300 mg/kg body ut/day for 5 days Aik. Following the administration of the VCM, the rats were studied with respect to behavior and appearance, body ut and food consumption, mortality, gross liver pathology, light microscopy of the liver and other c organs, and electron microscopy of the hepatic parenchyma. The study indicated that the incorporation of VCM-containing PVC powder into the diets of rats is an effective method for studying the long-term effects of oral administration of the VCM, When administered to the rats, the tumor response of the rat liver seemed to shift from an almost exclusive development of 30 (/) angiosarcomas at very hich levels of exposure to the exclusive induction of hepatocellular Tumors at low levels of exposure. There were also some evidence the ingestion of VCM in PVC enhanced the development of abdominal mesotheliomas and of mammary adenocarcinomas, (61 Refs) 03 ID o ro --4 94 AU AD TI SI SO LA AB Eckardt F ! Huliauan H J Oe Ruiter N ", Kappus N Institut fur Biologie, Gesellschaft fur STrahlen- und Umweltforschung, Ingolstadter Landstr. 1, D-8042 Neuherberg, W. Germany RAT HEPATIC VINYL CHLORIDE METABOLITES INDUCE GENE CONVERSION IN THE YEAST STRAIN D7RAD IN VITRO AND IN VIVO. ICDB/31/22237 Mutat Res; 91(4/51:331-390 1901 ENG D7RAD, an indicator strain of the yeast SOccharomyces cercvlsiae, was injected iv into male Wistar rats which were then exposed to vinyl chloride (VC) gas. After 24 hr of VC inhalation, the number of qene convertants scored as tryptophan prototrophic colonies in the yeast cells harvested from the liters of test animals were significantly increased compared with those of untreated controls. A model for VC Tumorigenesis is described. (40 Refs) x. c L e c 33 ft0 CO CO <o0 to CD 00005627 VINYL CHLORIDE PAGE 49 95 AU - Beilin JS AO - Control Action Div., Office Toxic Substances, United States Environmental Protection Agency, Washington DC TI - DON'T TAKE YOUR 'WORK` HOME WITH YOU. SI - ICDB/31/21751 SO - Occup Health Saf; 50(61:39-42 1981 LA - ENG AB - The recognition that occupational exposure to toxic chemicals can affect the worker and his or her family is a new concept in work-related disease. Various routes of family exposure are illustrated with respect to worker exposure to anesthetic cases> lead, vinyl chloride, dioxin, polychlorinated biphenyls, methylmercury, diethylstilbestrol, ionizing radiation, asbestos, beryllium, kepone, and others. Data concerning beryllium and asbestos exposure are discussed in detail. (20 Refs) 96 AU - Fortwengler HP ; Jones D J Espinosa E t Tamburro CH AD - (c/o Tamburro 1 Div. Digestive Diseases and Nutrition, Dept. Medicine, Health Sciences and Cancer Center, Unlv. Louisville, Louisville, KY, 40292 TI - EVIDENCE FCR ENDOTHELIAL CELL ORIGIN OF VINYL CHLORIDE-INDUCED HEPATIC ANGIOSARCOMA. SI - ICD3/81/19359 SO - Gastroenterology; 80(61:1415-1419 1981 LA ENG AS Previous reports of hepatic angiosarcoma have not clearly defined the cellular type from which this tumor arises, as evidenced by the terminology of endothelioma, Kupffer cell sarcoma, endothelial cell sarcoma, and hemangioendothelial sarcoma, etc, which have been used interchangeably. In addition, there has been no consensus on the separate entity of Kupffer and sinusoidal endothelial cells. In the work presented here, evidence for the endothelial cell origin of this tumor is provided by the demonstration of factor VIII, a known endothelial cell marker, in the tumor cells. Fluorescence due to the presence of factor VIII appeared intense in the tumor sinusoidal cells of all four vlns'l chloride-associa ted angiosarcomas studied, whereas normal liver sinusoidal lining cells showed negligible fluorescence. (Author abstract) (25 Refs) 97 AU AU AD TI SI SO LA AB Wisniewska-Knypl JM ; Sokal JA t Klimczak J 1 Dajniak A Bogdamkowa B Industrial Toxicology Dranch, Inst. Occupational Medicine, Teresy 8, 90-950 Lodz, Poland PROTECTIVE EFFECT OF METHIONINE AGAINST VINYL CHLOR 10E-MEDIATED 0EPPE5SICN OF MON-PPOTEIN 5ULPHIDRYL3 AND CYTOCHROME P-450. ICDB/81/I9108 Toxicol Lett! 8(31:147-152 1981 ENG The protective effect of OL-methionine (MET: 1 g/kq by qavaqe1 against vinyl chloride (VC)-medI ated hepatotox 1c1ty was assessed in rats induced by pnenebarbital (PB1 and exposed to 50,000 pom c c c c c c c c c c ;i; 'z* 00005628 VINYL CHLORIDE PAGE 50 c VC for 5 hr. The MET prevented the snermous liver hypertrophy! non-protein -SH depletion! destruction of P-950i and inhibition c of microsomal protein synthesis! which were seen after VC exposure without MET. The use of MET as a prophylactic agent in cases of occupational exposure To VC was suggested. (20 Refs) 98 AU - Kurliandskii 8A ; Stovbur NN ; Turusov VS AO - Municipal Sanitary Epidemioioqic Station! Moscow, USSR TI - SANITARY REGULATIONS OF VINYL-CHLORIDE. SI - ICDB/81/17968 SO -Gig SanitJ (3):79-75 1981 LA - RU5 A3 - Albino rats were treated with various doses of vinyl chloride (VC) to evaluate the general toxicity and carcinogenic effect of ( this substance so that its max permissible concentration (MFC) in the air of the working cone could be determined. The VC ccncentration of 5 mg/cubic meter is considered to be close to the threshold level in terms of general toxicity. A correlation was found between the development of tumors (including VC-specific angiosarcomas) and the VC dose. The results were considered to indicate that VC belongs to carcinogens of low activity (class IV of blastomogenic activity). It was recommended that the VC concentration of 0.1 mg/cubic meter be regarded as a MFC in the air of the working cone. (15 Refs) 99 AU - Koischwitc D , Laibach UK , Lackner K , Hermanutc D AO - Rontgenabteilung Medicinische Klinik, Radiologische Klinik der Universitat Bonn, 5300 Bonn-Venusberg, W. Germanv TI - VINYL CHLORIDE-INDUCED ANGIOSARCOMA AND HEPATOCELLULAR CARCINOMA OF THE LIVER. SI - IC03/81/171Q9 SO - Roefoi Fortschritte Auf Dem Gebiete Der Roentgenstralen Und Der) 139(31:233-290 1931 LA - GER AB - Presentation, diagnosis, and course of hepatic malignancies associated with exposure to vinvl chloride (VC) are illustrated through the case histories of three patients (59-57-yr-old men). The duration of known exposure to VC for these patients was 9-21 yr. Common signs at initial presentation included hepatomegaly, ThrombocyTcpenla, splenomegaiv, and history of diabetes mellltus. Two of the patients had elevated levels of alkaline phosphatase. Initial radiologic and histologic examinations revealed cirrhosis, siderosis, and/or fibrosis of the liver in all three patients. All of the patients developed esophageal varices in the course of the disease. The internal between initial presentation and diagnosis of hepatic tumors ranged from 1 to 11 yr', the presence of malignancies was confirmed through the use of celiacography , sonography, selective heoaticography, indirect sp 1 enppor t cgraphy, and computer tomograph'/. One patient developed osteolytic metastasis and cne developed multiple brain metastases. The conditions of the patients deteriorated rapidlv after the final diagnoses were made, and each of the patients died within a few mo of the final diagnosis. Autopsies revealed c c c ' r C (. 30 CO co CD O CO o 00005629 VINYL CHLORIDE PAGE 51 that The patients had hemangiosarcoma of the right hepatic lobe, mulTicentric angiosarcoma combined with mulTicentr1c primary hepatocellular carcinomai or metastatic angiosarcoma of the liver. Spontaneous occurrence of angiosarcomasi irregular presentation of such Tumors , and the relationship of the development of These tumors To VC exposure are discussed. (52 Refs ) 100 AU - Hallstrom I ; Sundvall A J Rannug U ; Grafstrom R ; Ramel C AO - Environmental Toxicology Unit, Wallenberg Lab., Univ. Stockholm, S-106 91 Stockholm, Sweden TI - THE METABOLISM OF DRUGS AND CARCINOGENS IN ISOLATED SUBCELLULAR FRACTIONS OF DROSOPHILA MELANOGASTER. I. ACTIVATION OF VINYL CHLORIDE, 2-AMINOANTHRACENE AND BENZOCAIPYRENE AS MEASURED BY MUTAGENIC EFFECTS IN SALMONELLA TYFHIMURIUM. SI - ICDB/81/13999 50 - Chem Biol Interact; 39(2)1129-193 1931 LA - ENG AB - The capacity of microsomal fractions from different Drosophila strains To activate Three premutagens, 2-aminoanthracene (2-AA) vinyl chloride (VCM) and bengo (a)pyrene (BP) was investigated, using Salmonella typhimurium as The indicator organism, A significant increase in the mutation response in the Salmonella test system was obtained with all Three substances in the presence of a metabolising system (S9) from Drosophila larvae. 2-AA was converted to highly mutagenic metabol1te(s ) by The Drosophila S9 and the mutagenic effect was further increased after pretreatment with Aroclor 1259 (PCD) or beta-naphthoflavone (BNF). BP has only marginal mutagenic effects, causing less than a 2-fold increase in The number of mutants over the control. The data indicate that the metabolic conversion of BP is different in the Drosophila as compared to the rat liver microsomal fraction. In accordance with mutagenic data on Drosophila in vivo, vinyl chloride was a fairly weak mutagen in this Drosophila-Salmonella in vitro system, (Author abstract) (92 Refs) 101 AU - Stott WT ; Watanabe PG AD - Toxicology Res, Lab., Dow Chemical, 1303 Building, Midland, MI, 98690 TI - RISK ASSESSMENT OF EXPOSURE TO VINYL CHLORIOE. 51 - ICOB/81/12697 SO - Pure Appl Chem! 53(2)1593-595 1931 LA - ENG AB - Carcinogenic risk estimation of human exposure to vinyl chloride (VC) was determined by utilising laboratory animal data on the chronic bioassay of VC, VC pharmacokinetics and VC macromolecular interaction. The in-pact of these data upon the type of risk VC may pose to humans and the selection of appropriate mathematical models to quantitatively estimate 'risk' are discussed, (Author abstract) (6 Refs) c c c ( c c c L L L 00005630 VINYL CHLORIDE PAGE 52 c 102 AU - Heckman JH c AD - Washington, DC, 20036 c TI - REGULATORY STATUS OF POLYVINYL CHLORIOE, 1980. SI - ICD8/31/12696 SO - Pure Appl Chem; 53f2 ) :5S3-592 1981 c LA - ENG c cAB - The regulatory history of vinyl chloride and polyvinyl chloride, particularly at the Occupational Safety and Health Acministration i the Food and Drug Administration, and the Environmental Protection Agency, is reviewed in detail. It is evaluated in terms of perceptions of the soundness of c( governmental actions and also as an example of responsible industry achievement. Despite constant reevaluation by the involved agencies, the urgency that initially cnarecterized their actions regarding vinyl chloride has been tempered by continuing improvements in monomer management and recently maturing concepts of risk assessment. The most valuable benefit to flow from the vinyl chloride experience may well be its influence in focusing attention on the need for more objective risk assessment as an accepted basis for all regulatory decision-making. (Author JJ (fi/o) abstract ) (27 Refs) 103 AU AD TI 51 SO LA AB Dannaher CL ; Tamburro CH ; Yam LT Columbus Hosp. Regional Oncology Center, Post Office Box 5013, Great Falls, HT, 59403 OCCUPATIONAL CARCINOGENESIS: THE LOUISVILLE EXPERIENCE WITH VINY' CHLORIDE-ASSOCIATED HEPATIC ANGIOSARCOMA. ICD3/81/11773 Am J Med; 70(2 ):279-237 1931 ENG Hepatic angiosarcoma in man was first associated with exposure To vinyl chloride in Louisville, Kentucky, where it was identified in 10 persons from a single vinyl chloride polymerization plant! clinical manifestations are summarized herein. Following prolonged exposure to vinyl chloride, the onset of this disease is insidious and the clinical picture is that of nonspecific hepatic injury with mildly abnormal biochemical liver test results. Careinoembryonic antigen and alpha fetoprotein are undetectable. Radionuclide and angiographic studies of liver show characteristic but nondiagnostic abnormalities. A definite diagnosis is usually made only by open liver biopsy. Treatment is unsatisfactory but chemotherapy seems to prolong survival, Av survival from diagnosis is about 12 mo. Overt luer failure usually occurs only as a preterminal event and was the majer cause of death in all of our patients. Preventive measures are now in effect in The plant. This experience illustrates the importance of the clinician in occuoaTlonally-rela ted cancer. (Author abstract) (S3 Refs) 03 CD O 03 t l c c L 33 3 (/> Z 0E6EV 'y-*'rrlvU`u'r:c-''T''"r7'--^ejhTf= c ( c. c c 00005631 VINYL CHLORIDE PAGE 53 104 AU - Popper H ; Selikoff IJ AO - Stratton Lab. Study Liver Diseases Environmental Sciences Lab.t Mount Sinai Sch. Medicine, City Univ. New York, One Gustave Levy Place, New York, NY, 10029 TI - UMAT IS ENVIRONMENTAL PATHOLOGY? SI - ICDB/01/11378 SO - Am J Med; 70(21:213-220 1931 LA - ENG AB - Environmental hazards that effect man have been of growing concern. Data concerning these hazards is accumulating. This information comprises the field of environmental pathology. The liver serves as a study model for many environmental injuries since it is the principal target of many hazardous environmental agents. However, hepatocellular carcinoma, with the exception of aflatoxicosis and vinyl chloride, is not often the result of environmental carcinogens. Continued vigilance is encouraged since other agents may yet be detected that resemble vinyl chloride. Two proposed restrictions of the definition of environmental pathology reflect the dose and duration of exposure and the source of exposure. These restrictions lessen unjustified concerns and focus on potentially greater hazards, (12 Refs) 105 AU AO TI SI SO LA A3 - Spengler S I Singer B - Dept. Molecular Biology and Virus Lab., Univ. California Berkeley, Berkeley, CA. 94720 - TRANSCRIPTIONAL ERRORS AND AM3IGUITY RESULTING FROM THE PRESENCE OF 1,NS-ETMENOADEN0SINE OR 3,N4-ETHENCCYTIDINE IN POLYRIBONUCLEOTIDES. - ICD3/S1/10393 - Nucleic Acids Res; 9(2) = 365-373 1931 - ENG - The compounds 1,N6-ethenoadenosine (epsilonA) and 3,N4-ethenocytidine (epsilonCI in copolymers with unmodified nucleosides were transcribed using DMA-dependent RNA polymerase in the presence of Mn + + . Nearest neighbor analysis of the products showed that epsilonA directed incorporation of A greater than U greater than C while epsilonC directed the incorporation of U greater than or equal to A much greater than C. Neither directed G into the complementary polymer. Such m1sincorporations resulting from epsilonA and epsilonC, compounds that are formed in vivo by the carcinogen vinyl chloride, may ha"e a biological role as promutagens. (Author abstract) (28 Refs) 106 AU AO TI SI SO LA Barbin A I Bartsch H ; Leconte P ; Redman M 1 0iv. Environmental Carcinogenesis, Internetional Agency Res. Cancer, 150 cours AlberT-Thomas , F-69372 Lyon Cedex 2, France STUDIES ON THE MISCODING PROPERTIES OF 1,N6-ETHENOADENINE AN0 3.N4-E THENOC YTOSIME, 0MA REACTION FRCDUCT3 OF VINYL CHLORIDE METABOLITES. DURING IN VITRO DMA SYNTHESIS. ICDB/81/10392 Nucleic Acids Res; 9(2) = 375-337 1931 ENG 00005632 VINYL CHLORIDE PAGE 54 AB - The compounds 1>N6-ethenpadenine (epsilonA) and 3,N4-ethenocytosine (epsilonC) are formed when electrophilic vinyl chloride (VC) metabolites, chlorethylene oxide (CEO) or chloroacetaldehyde (CAA) react with adenine and cytosine residues in DNA. They were assayed for Their miscoding properties in an in vitro system using Escherichia coli DNA polymerase I and synthetic Templates prepared by reaction of poly(dA) and poly(dC) with increasing concentrations of CEO or CAA, Following the introduction of etheno groups> an increasing inhibition of DNA synthesis was observed. dGMP was misincorporated on CAA- or CEO-Treated poly(dA) templates and dTMP was mis incorporated on CAA- or CEO-treated poly(dC) templateSi suggesting that eosilonA and epsilonC may miscode. The error rates augmented with the extent of reaction of CEO or CAA with the templates. Base-pairing models are proposed for the epsilonA-G and eosllonC-T pairs. The potentially miscoding properties of epsilonA and epsilonC may explain why metabolically-activated VC and its reactive metabolites specifically induce base-pair substitution mutations in Salmonella typhimuriurn. Promutagenic lesions may represent one of the initial steps in VC- or CEO-induced carcinogenesis. (Author abstract) (53 Refs) 107 AU - Dannaher CL i Tamburro CH ; Yam LT AO - Regional Oncology Centeri Columbus Hosp.i P. 0. Box 5013i Great Falls, MT, 59403 TI - CHEMOTHERAPY OF VINYL CHLORIDE-ASSOCIATED HEPATIC ANGIOSARCOMA. 51 - ICDQ/S1/09500 SO - Cancer; 47(3)1466-469 1931 LA - ENG AB - The use of systemic chemotherapy was studied in a group of four patients who had hepatic angiosarcoma in association with exposure to vinyl chloride. All of the patients received adriamycin 60 mg/square meter (m2) !v every 3-4 wK and in three patients this was combined with Cytoxan 600 mg/m2 and methotrexate 20 mg/n,2. Three patients had an objective response lasting 4, 9, and 10 mo. One patient had stable disease for 10 mo. Responding patients maintained an excellent performance status during therapy. Following evidence of progressive disease, patients died in 3, 4, and 6 mo. Survival from the time of diagnosis was 11, 13, 15 and 53+ mo. Sufficient data are not available from these patients to recommend a specific drug or combination for use in hepatic anqiosarcoma, but our data indicate that chemotherapy can improve quality and duration of survival. (Author abstract) (12 Refs) 103 AU - Spenqler SJ i Singer BA AO - University of California, Berkeley, CA, 94720 TI 1,N(6)-ETHENOAOENOSINE AND 3,N(4 I-ETHENOCYTIDINE IN POLYRIBONUCLEOTIDES LEAD TO TRANSCRIPTIONAL ERRORS AND AM3IGUITY (MEETING ABSTRACT), SI HERN/32/09774 SO J Supramol Struct; Suppl5:212 1931 LA ENG 00005633 VINYL CHLORIDE PAGE 55 AB - The human carcinogen, vinyl chloride, 13 metabolically converted by The microscmal cytochrome P-450-dependent monooxygenases to the reactive compound chloroethylene oxide, which also rearranges to form chloroacetaldehyde. These compounds react with adenosine and cytidina to form the fluorescent etneno derivatives, 1,N( 6)-ethenoadenosine (epsilonA) and 3,M(4)-ethenoeytidine (epsilon C). He have synthesized C and A ribccolvmers containing varying amounts of epsilon C cr epsilon A and Transcribed Them using DMA-dependent RNA polvmerase in the presence of Mn. Nearest neigh.bor analvsis of the Transcripts showed that epsilon A acted more like U than like A and more like A Than G. ETheno C, on the other hand, acts primarily like A, though simulation of U and G also occurred, Neither derivative behaved like C in These copolymers . Such Transcriptional errors may indicate the nature of the mutagenic lesion involved in vinyl chloride carcinogenesis, since it has been shown that even at low doses these derivatives accumulate in DMA. (1 Ref) 109 AU - Hall JA ; Saffnill R AD - Paterson Laboratories, Christie Hospital & Holt Radium Institute, Manchester M2 0 ?5)< TI - CIILCROACETALDEHYDE, A VINYL CHLORIDE METABOLITE, INDUCES ERRORS DURING IN VITRO DNA SYNTHESIS (MEETING ABSTRACT). SI - HERN/82/07203 SO - 22nd Annual General Meeting of the British Association for Cancer Research, April 13-15, 1931, Keele, Staffordshire, England. The Association 67 pp.> 1961. LA - ENG AB - Chloroacetaldehyde (CA), a rearranged metabolic product of the human carcinogen vinyl chloride has been shown to be mutagenic in certain microbial systems as well as towards mammalian cells. CA has been reacted with the alternating DMA-like polymers poly (d eoxvadenylate-thvmi dvlat e ) (poly ( dA-dT )) and poly(deoxycytidylate-guanylate )(poly(dC-dG ) ) when, as with DMA eTheno-adducts of the adenine and cytosine bases are formed. These treated polymers, when used as templates for E coll DMA polymerase I, show a decreased ability to direct DMA synthesis. This is accompanied by an increase in the relative levels of non-compiementary nucleotides incorporated into the newly synthesized DMA-like material. This increased with the amount of modified base present in the Templates used. With The poly(dA-dT) templates one deoxythymidine monophosphate residue was incorporated for el,ei-y approx 60 e thenoaden i ne residues present while no cieoxycy t i d i lie mor.oohocoh.i t e ml s 1 ncorppra 11 on was detected. One mlsincorporatiOn of deoxv AMP or deoxy thyi i i d l ne moncphocphate occurred in the presence of approx 30 and 60 e Ther.ocv t cs i ne residues respectively in The polv(dC-dG) Ten plates. For the modified poly (dC-aS) templates a nearest neighbor analysis shows that the ma)orlty of The errors were incorporated opposite The cytosine (or modified cytosine) bases. Extensive analyses of The modificaticos present in the Templates indicate that the mislncprporations observed are not due to the presence of apurinic sites cr to The formation of uracil or 00005634 VINYL CHLORIDE PAGE 56 xanthine by deamination of the the cytosine or adenine bases respectively, tie conclude that the non-complement ary nucleotide incorporations probably arise from The presence of etheno-adducts in the Templates used, (no Refs) 110 AU - Rice J t FriTh C AO - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, ITO TI - CRITERIA FOR ESTABLISHING ORGAN SPECIFICITY IN EXPERIMENTAL CHEMICAL CARCINOGENESIS (MEETING ABSTRACT). SI - HERN/62/05944 SO - Organ and Species Specificity in Chemical Carcinogenesis Symposium, March 2-4, 1961, Raleigh, North Carolina. U.S. Environmental Protection Agency 96 pp., 1931. LA - ENG AB - Chemical carcinogens often have different effects in different species! a given agent causes neoplasms in different organs and tissues depending on the species, sex, and age of the recipient and on the magnitude, schedule, and route of exposure. Such differences can provide a means of experimentally distinguishing interactions of carcinogen with target cells that are significant fcr carcinogenesis. A given agent mav affect different organ systems in different species: aromatic amines, for example, are preferentlally carcinogenic for the urinary bladder in man, non-human primates, and the Syrian hamster, but are more likely to affect the liver or intestinal mucosa, or even remote organs such as Zymbal's gland in the rat, and are totally ineffective in other species That lack, the metabolic capacity To N-hydroxylate and conjugate these compounds. Alternatively, a given agent nay affect the same oraan system in different species, but the Target cell may vary. Di ethylni trosamir.e (DEN) is carcinogenic for hepatocytes in most species, including the mouse, rat, Syrian hamster, and dog, but in some species, including the mouse, rat, and doq> DEN is also carcinogenic for the hepatic blood vessels. Conversely, vinyl chloride is preferentially carcinogenic for the blood vessels of the liver in man and in rats and mice, in which species both vascular and epithelial tumors may also be induced at extraheoatic sites. As an indication of the importance of systematic pathological evaluation in such studies, a comparison of gross and microscopic evaluation of tissues from mice given 2-asetylaminofluorene is presented, (no Refs) 111 AU AU AD TI SI SO LA AB - Hatch GG Mamay PO ! Christenson CC ! Casto BC > Langenbacn R - Nesno-.-i S - Northrop Services, Inc, Research Triangle Park. NC - IN VITRO TRANSFORMATION OF HAMSTER EMBRYO CELLS EXPOSED TO GASEOUS OR VOLATILE CHLORINATED HYDROCARBONS (MEETING ABSTPACT). - HERN/02/05251 - Proc An Assoc Cancer Pas', 22:119 1931 - ENG - Chlorinated organic comoounds , many of which are "olatile licuids or gases hai'e widespread industrial and environmental importance and have a suspected role in the etiology of certain human ;:-'':\V':!' C ;. C / / ' (. ?** TrrL*?* C i. 00005635 VINYL CHLORIDE PAGE 57 112 AU AD TI SI SO LA AB 113 AU AD TI SI SO LA A3 cancers. Methods have been developed in our laboratory for exposing cultured cells to gases or vapors of volatilised liquids. These techniques allow the evaluation of the genotoxic effects of these agents in in vitro systems. Primary hamster embryo cells were treated with acetone (negative control) or varying concentrations of the following chlorinated hydrocarbons: lil.l trichloroethane> (TCE)t dichlorcmethane (DCM): 1.1-dichlorcsthane (DCE1); 1,2 dichloroethane (DCE2) or vinyl chloride (VC), and subsequently assayed for cell survival and an increased sensitivity To SA7 virus transformation. Treatment doses extended from Toxic to several nontoxic doses. Samples from each test chamber were analysed by standard gas chromatograohic Techniques and actual concentrations determined. TCEt DCM. DCE1> DCE2f and VC treated cells demonstrated an increased frequency of Trans formatlon by SA7 virus. Treatment chamber ecncentrations of chemicals producing a maximal response ranged from eoprox 11-26 uq/cm3 (TCE), 22-72 ug/cm3 (DCM), 14-73 ug/cm3 (DECO and 194 ug/cm3 (VC), The length of chemical treatment and the time interval before subsequent addition of transforming virus was critical and dependent on the chemical evaluated. Incorooration of These compounds into liquid cell culture medium were unsuccessful or produced only a weaK enhancement response. Treatment of hamster cells with gases or the vapor phase of volatile compounds yielded reproducible and quantitative results, (no Refs ) Kucerova M Genetic Department, Postgraduate Medical Institute, Prague, Czechoslovak i a COMPARISON OF DIFFERENT CHROMOSOMAL DAMAGE CAUSED IN VIVO IN HUMAN CELLS BY DIFFERENT CHEMICAL MUTAGENS (MEETING ABSTRACT). HERN/81/02903 Eleventh Annual Meeting of the European Environmental Mutagen Society, July 6-11, 1981, Budapest, Hungary The Society, 1931. ENG Summarizing for cytogenetic studies of people exposed in vivo to different mutagens (epiehlorhydrme , vinyl chloride, imuran and cyclophosphamide) we compare The resulting chromosomal damage, which was very similar. However, the chromosomal aberrations in human lymphocytes detected after exposure to chemicals in vivo on whole differ enormously from chromosomal aberrations discovered in human lymphocytes after exposure to radiation in vivo, (no Refs) Sram RJ Institute of Hvqiene and Epidemiology, Prague, Czechoslovakia MONITORING THE OCCUPATIONAL EXPOSURE TO MUTAGENS - FACTS AMD IDEAS (MEETING A3STRACT ) . HERH/81/02G47 Eleventh Annual Meeting of The European Env 1 ron-.ental Mutagen Society, July 6-11, 1931, Budapest, Hungary The Society, 1931. ENG The cytogeneTic analysis of peripheral lymphocytes, which proved R&S 139037 4 c 00005636 VINYL CHLORIDE PAGE 53 c to be o feasible bioindicator of genetic damage to somatic cells of workers occupationally exposed to mutagens may be used ns a c tool for checking acceptnbi1ity of MAC levels established for them in work environment. This approach was verified on groups exposed to dimethyl formamidei eplchlorohydrin, epoxyresms, haloethers, hydrocarbons, styrene, vinyl chloride. A possible c antimutagenic effect of vitamins was checked on the group treated by the ascorbic acid, its influence to the chromosome aberrations frequency is presented. The examination of mitotic index and blastic transformation in lymphocytes as well as Hb alkylation in R6C seems to be the necessary part of genetic monitoring, if individual risk should be evaluated, (no Refs) 114 AU Bendix 5 AO Bendix Environmental Research, Inc., San Francisco, CA TI FIREFIGHTER EXPOSURE TO ORGANIC CARCINOGENS (MEETING ABSTRACT), SI HERN/61/02123 SO J Occup Med; 23(4):305 1961 LA ENG ( AO Burn, acute cardiac and respiratory hazards have been the past focus of attention to medical problems of firefighters . Firefighters are exposed to complex chemical mixtures of vaporized, off-gassed, decomposed and newly synthesized organic chemicals under conditions where they rarely know what they are breathing or what special chemicals hazards they may encounter. Self-contained breathing apparatus may not be worn, may not be available, or may not be properlv maintained to preserve designed (. function. It is time to look at the long-term consequences of firefighter exposure to vinyl chloride, dioxins, urethane, benzene, tetrachioroethane, polvaromatic hydrocarbons and other carcinogens. Record-keeping and medical follow-up need tu improvement, (no Refs) 115 AU AD TI SI SO LA AB Serrentino R i Gervasi FG Laboratorio di Mutaqenesi e 0ifferenziamento, C.N.R., Pisa, Italy PHOTOMETRIC DETERMINATION OF MICROSOMAL EPOXIDE HYDROLASE ACTIVITY BY THE 4-(P-NITROBENZYL)PYRIDINE TEST. ICQB/31/20440 Boll Soc Ital Biol Sper; 56(221:2393-2397 1960 ITA A simple photometric assay for the determination of the microsomal epoxide hydrolase activity by the 4-(p-nitrobenzyl) pyridine test is described. Microsomal epoxide hydrolase plays a key role in the detoxification of olefinlc and aromatic hydrocarbons which are transformed into mutagenic and carcinogenic epoxides (such as vinyl chloride and benzol a Ipyrene) in the body. (8 Refs) f.V: ii ( cr*. 00005637 VINYL CHLORIDE PAGE 59 c c (' (. r-\&r4 116 AU - Lijinsky U ; Andrews AW AO - Chemical Carcinogenesis Program, Frederick Cancer Res. Center, Frederick, HO, 21901 TI - HUTAGENICITY OF VINYL COMPOUNDS IN SALMONELLA TYPHIHURIL'H. SI - ICDB/81/20063 SO - TeraTogenesis Carcinog Mutagen! 1(31:259-267 1980 LA - ENG AB - The mutagenic activities of 18 compounds that are structurally related to vinyl chloride were assayed in Salmonella typhimurium tester strains TA1535, TA1537, TA1538, TA98, and TA100 In the presence and absence of liver microsomal preparations. Ten compounds were nonmutagenic in all strains. Mutagenic activities in one or more strains were found, however, for acrolein, acrolein diethylacetal, allyl alcohol, acrylonitrile, allyl bromide, crotonaldehyde> crotyl alcohol, and vinyl bromide. (18 Refs 1 117 AU - Fabricant JD ! Chalmers JH AD - Dept. Preventive Medicine and Community Health, Univ. Texas Medical Branch, Galveston, TX, 77550 TI - EVIDENCE OF THE MUTAGENICITY OF ETHYLENE DICHLORIDE AND STRUCTURALLY RELATED COMPOUNDS. SI - ICDB/S1/19170 SO - Banbury Rep Ser; 5:309-329 19S0 LA - ENG AB - The short-term mutagenicity assays for ethylene dichloride (EDC) and its structural analogs are reviewed. The most widely used short-term mutaqenicity tests are Salmonella mammalian mlcrosome assay (Ames test), yeast or Neurospora, sex-linked recessive lethal mutation in Drosophila, or in vitro studies in cell culture. Positive results were reported for EDC, vinyl chloride, vinylidene chloride, and trichloroethylene> while perchloroethylene showed mutagenic activity in Salmonella and in Escherichia coli systems. (36 Refs) 118 AU AO TI SI SO LA AB Infante PF ', Marlow PB Office of Carcinogen Identification and Classification, Occupational Safety and Health Admin., Washington, DC, 22010 EVIDENCE FOR CARCINOGENICITY OF SELECTED HALOGENATEO HYDROCARBONS INCLUDING ETHYLENE DICHLORIDE. ICD3/81/1A169 Banbury Rep Ser! 5=287-308 1960 ENG The experimental and epidemiological studies on the carcinogentcity of 10 halogenated hydrocarbons related to vinyl chloride (VC) are reviewed. All 10 chemicals induced malignant tumors in both rats and mice. Liver was the target organ -or 9/10 substances. Ethylene dichloride induced carcinomas of The forestomach and liver and adenocarcI nomas of the mammary gland in both rats and nice, while spleen angiosarcomas were recorded only in rats. Ethylene dtbromlda induced tumors in the greatest number of organs. Analysis of cancer Incidence among the uorkers exposed R&S 139038 33 Q (fl - w (0 O CP to c 00005633 VINYL CHLORIDE C PAGE 60 :Vi~'rj ^';" ;' c rV ' A' w {V. (.. .- .-; /v-'. - ' ' > ' ' ' r * * * ,,J * ,' l. ` *Y-' * r4'**'* ` '* V V- - r` < i..V. ` .] " lo certain halogenatad hydrocarbons suggested an elevated risk of lung cancer among The workers exposed To epichlorohydrin. (1 Ref) 119 AU - Johnson MU AD - B. F. Goodrich Co.. Akron, OH, A4313 TI - MEDICAL ASPECTS OF ETHYLENE 0ICHL0RIDE IN THE WORKPLACE. 51 - ICD3/S1/19166 SO - Banbury Rep Seri 5:Z57-263 1930 LA - ENG AB - The efficacy of regular periodic medical examination for workers exposed To eThylene dichloride (EDC) is discussed. IT is emphasised ThaT alThough a periodic medical examinaTion can deTec* The early clinical signs of chronic exposure To cerTain chemicals (organophosphorous insecTicldes ), iT is quiTe useless for The evaluation of Long-Term effecTs of exposure To oTher chemicals such as vinyl chloride for which EDC is a raw maTerial. (no Refs ) 120 AU - Ames B ; InfanTe P ReiTp R AD - Dept, Biochemistry, Univ. California, Berkeley, CA TI - ETHYLENE DICHLCRIDE: A POTENTIAL HEALTH RISK? SI - ICDB/61/19155 SO - Banbury Rc-p 5er. Vol. 5, 350 pp. , I960. LA - ENG AB - This vol contains The papers presented at The four sessions of a conference held To explore The potential carcinogenicity for humans of eThylene dichloride (EDC) and related halogenated hydrocarbons . The subjects of The individual sessions were The mutagenicity and carcinogenicity of EDC, toxicology and other Topics, uses of EDC and worker exposure, and related chemicals. AlThough There is no evidence ThaT EDC causes birth defects or reproductive effects, animal studies and Salmonella and Drosophila assays suqgestsd ThaT it may pos a carcinogenic and a muTaqonic hazard. Of the other haloqcnated hydrocarbons discussed, vinyl bromide, vlnly chloride and ethylene dibromtde were described as being careinogenlc. Results of preliminary assessment of human exposure To EDC Indicated that qreater than 99of the exposures are in the range of 10-990 parts pettrillion. These results suggested that The relative human risk is low. ( 332 Refs ) 121 AU - Sokal JA ; Baranski B flajka J ; Rolecki R i Stetkiewicr J AU - Ivanova-Cheml shanska L Vergleva T Antonov G I MirKova E AU - KolakowsKi J t Scendcikowski S ; Wrcblewska K AD - Inst. Occupational Medicine, P. 0. Box 199, 90-950 Lode, Poland TI - EXPERIMENTAL STUDIES ON THE CHRONIC TOXIC EFFECTS OF VINYL CHLORIDE IN RATS. SI - ICC3/81/13393 SO - J Hyg Epidemiol Microbiol Immunol (Prana); 2A(3):2S5-29A 1930 LA - ENG A8 - Th^ Time course of chronic Toxic effects of 'Mnyl chloride (VC) in Wistar rats was investigated. Pats were exposed in dynamic inhalation chambers To VC at concentrations of 50 ppm, 500 ppm, c c ( f k V l c c. L L L 00005639 VINYL CHLORIC PAGE 61 and 20000 ppin for 10 mo > 5 hr/day, 5 days Aik. Apparent treatment-related pathomorphological changes developed in the liver and testes; the liver changes appeared earlier and at lower VC concentrations than the testicular changes. Body wt decreased in the VC-treatad rats. These changes increased with the duration of exposure. Increased relative wt of some organs and slight hematological and biochemical changes in blood during the course of the experiment also were observed. Ewen at the lowest VC concentration some Toxic effects were observed) including depression of body wt increase) increased relative wt of some internal organs, slight hematological and biochemical changes and fluctuations) and uiTrasTrueturai changes in heoatocytes and the tendency for an increased incidence of histological liver changes. Based on the assumption that 50 ppm is the threshold concentration of VC for rats> a level of 5 ppm was estimated to be The safe exposure limit in industry with respect to systemic effects . (27 Refs ) 122 AU - TarKowski S ; Hisniewska-Knypl JM ; Klimczak J ; Draminski W AU - Nrobleuska K AD - Div. Industrial Toxicoioqv> Inst. Occupational Medicine) ul. Teresy 8, 90-950 Lodz, Foland TI - URINARY EXCRETION OF THICDIGLYCOLLIC ACID AND HEPATIC CONTENT OF FREE THIOLS IN RATS AT DIFFERENT LEVELS OF EXPOSURE TO VINYL CHLORIDE. SI - IC0B/B1/I369S 30 - J Hyg Epidemiol Microbiol Immunol (Praha); 29(31:253-261 1930 LA - ENS AB - Male Wistar rats were exposed to vinyl chloride (VC: 50r 200> 500) l(000i or 20)000 ppm) one time for 5 hr or for 6 mo (5 hr/day/5 doys/wk)) and the oxidation of inhaled VC was assessed by measuring The urinary excretion of Thiodiglycol1ic acid (TDGA), The conjugation of VC metabolites was assessed bv measuring the hepatic contents of nonprotein thiols. The rate of urinary excretion of TDGA after VC exposure depended on the activity of microsomal monooxvgenase. TDGA was found in the urine 29 hr after exposure to 50 ppm VC; urine excretion of TOGA increased with increasing VC exposure. In general) There were no significant differences in TOGA excretion in rats exposed to either single or long-term exposure) except That a 6-mo exposure to 20,000 ppm VC resulted in a lowered TDGA e<cretion compared to that observed after a single 20,000-ppm exposure. Excretion of TDGA in exposed rats was accompanied by a depression in The nonprotem Thiol content in The liver. PretreatmenT of The rat3 with an inducer or inhibitor of cytochrome P-950 synthesis resulted in an increase or complete inhibition, respectively, of TDGA excretion. Pretreatment of rats that had been exposed to 20,000 ppm VC with either phenooarbItal or CoCl2 increased the nonprotein sulfhydryl hepatic content (6.0 +-0.3 or 8.9 + -0.9 micrcmples (umoiesl/q liver, respectively), compared to rats that had been exposed to 20,000 ppm VC alone (2.8 *-0-3 umoles/q). Glutathione reductase levels In woles sulfhydryl/q liver/15 min were 126 -f-6, 209 +-21, and 167 +-13 for rats exposed To R&S 139041 c 00005640 VINYL CHLORIDE PAGE 62 ( ( V..- T.^'i:k*ViTN'*jFKVv7'3*:^'Tfe?<csTf**fYwdr; t.. K i .''. - v. 20,000-ppm VC onlyi for VC plus phenobarbi tal pretreatment, and for VC plus CoCl2 pretreatment, respecTively. (20 Refs ) 123 AU AO TI SI SO LA A3 h'anawa K 5 Yamada S ; Sunuki H ; Nagayo T First Dept. Pathology, Aichi Cancer Center, Chiku3D-ku, Nacoya 464, Japan EFFECTS OF SODIUM CHLORIDE ON GASTRIC CANCER INDUCTION BY N-METHYL-N'-NITRO-N-NITROSOSUANIOINE (MNNG) IN RATS (MEETING ABSTRACT). ICDB/S1/10700 Proceedings of the 39th Annual Meeting of the Japanese Cancer Association held in Tokyo, 5-7 November, 1930. The Japanese Cancer Association, Tokyo 170, Japan, 367 pp., 1930. JFN Seven-wk-old male and female Nistar rots (U'3N/kob) were given a saturated aqueous NaCl soln with N-msthyl-N'-nitro-N-nitrosoguanldine (MNNG; Group 1), NaCl at 50/ saturation with MNNG (Group 2), MNNG alone (Group 3) or the saturated saline soln aicne (Group 4). The saline soln (1 ml) was administered through a vinyl tube cnee a wk and 25 mg of MNNG per liter was added to the drinking water dail\', both for 20 wk . The rats were then given tap water to drink and examined. Gastric cancers were produced in 1/4, 4/7, 0/10 and 0/7 of the male rats, and in 4/11, 4/7, 2/3 and 0/7 of the female rats, in Groups 1, 2, 3, and 4, respectively. The incidence of gastric tumors was higher in the groups given MNNG * a saline soln than in the group given MNNG alone, and the group given the 50/ saturated saline soln had a higher incidence of gastric tumors than the group given the saturated saline soln in both males and females. The incidence of cancer in the rats qiven both MNNG and a saline soln did not differ significantly with the sex of the rats, but tumors were produced only in the female rats when MNNG was administered alone. Most of the tumors were restricted to the pyloric area (11/15) and they were histoloqical1v highly atypical adenoma (3/15) or weil-oifferentiated adenocarcinoma (12/15). In conclusion, NaCl was found to have a promotive effect on MNNG-induced gastric cancer, (no Refs) 124 AU AD TI SI SO LA AB Veitman G UniversitatshautklinIk, 5igmund-Freud-Str. 25, 0-5300 Bonn 1, W. Germany CLINICAL FINDINGS AND ASPECTS OF OCCUPATIONAL MEDICINE IN VINYL CHLORIDE DISEASE. ICDB/81/10010 Dermatol Monatsschr; 166(11)1705-712 1930 GER Symptoms caused by lonq-term exposure to vinyl chloride (VC) are reviewed, and health risks (including cancer) associated with VC exposure are discussed. Physical properties of VC are briefly outlined, and industrial occupations in which workers risk exposure to this chemical are noted. Effects of lonq-term exposure to VC are described with respect To clinical manifestations, sc in'lqraphlc and roentgenologlc findings, and 00005641 VINYL CHLORIDE PAGE 63 laboratory findings; the relative incidence of the mo3t frequent symptoms is noted. Paroclinical findings in patients with long-term VC exposure are discussed with respect To changes in skin> alterations in blood vessels or bone, liver damage, and chromosome anomalies. The possibility that VC exposure results in CMS symptoms is considered. The course of VC-caused symptoms is described for patients with continu'd exposure to VC and patients for whom VC exposure is eliminated; emphasis is placed on the reversal of many symptoms in patients no lonqer exposed To VC. In cons i daration of The potential health effects of VC, measurement of VC damage and limits of VC exposure are discussed. The relationship between VC exposure and the development of angiosarcoma is noted. (52 Refs) 125 AU - KrajewsKi J ; Dobecki M i Gromiec J AD - Dept. Chemical Air Pollutants, Inst. Occupational Medicine, Lodz, Poland TI - RETENTION OF VINYL CHLORIDE IN THE HUMAN LUNG. SI - IC0B/S1/09869 SO - Br J Ind Med; 37(4):373-374 1980 LA - ENG AB - Experiments with volunteers showed that 42k of an inhaled dose of vinyl chloride is retained in The lungs. This value is independent of the concentration of vinyl chloride in the air. Elimination of vinyl chloride Through the lungs is negligible since its concentration in expired air decreases immediately after the cessation of exposure. (Author abstract) (4 Refs) 126 AU - Natarajan AT ; Obe G AD - Dept. Radiation Genetics and Chemical Mutagenesis, Silvius Laborat or i es, llniv, Leiden, Wasenaarseweg 72, Leiden, The Netherlands TI - SCREENING OF HUMAN POPULATIONS FOR MUTATIONS IMOUCED BY ENVIRONMENTAL POLLUTANTS: USE OF HUMAN LYMPHOCYTE SYSTEM. SI - ICOB/S1/09352 SO - Ecotoxicol Environ Saf! 4(4):468-481 1980 LA - ENG AB - The frequencies of chromatid qaps (G) and breaks (B' ), i sochromat i d/chromosome breaks ( B-1 ), chromatid translocations (RB'l, dicentrics (DIC), rings, balanced translocations ( BT ), and inversions (INV) in phytohemagqlu11nln-sT i mulated 43-hr peripheral blood lymphocvte (TBL) cultures may be a useful means of monitoring exposure to environmental mutagens and carcinogens. In a 72-hr PEL culture, the cells are In the second Or Third metaphase and many chromosome aberrations ha'<e been lost. The reported av frequency of exchange-type aberrations (DIC, R3', and rings) in 43-hr PCL cultures is 9.64(4) metaphases. The reported frecuencies of gaps, B', and B" are higher and vary widely, perhaps because different criteria may be used to distinguish them. In the PBL of irradiated persons (Hiroshima and Nagasaki residents or patients given radiotherapy for ankylosing spondylitis), the frequencies of DIC and rings decline with time, but reciprocal Translocations persist at an unchanged high 00005642 VINYL CHLORIDE PAGE 64 frequency for many yr. Increased frequencies of exchange-type a.berrations (DICi rings, and R8` ) and breaks (B* and 8') have been reported in the FBL of alcoholicsf heavy smokers, and workers exposed to high concentrations of vinyl chloride and other mutagens. Infectious hepatitis and mononucleosis also increase The frequency of chromosomal aberrations, but the long-term persistence of these effects is unknown. The frequencies of micronuclei and hypoxanthine guanine phosphoribosylTransferase deficiency (associated with 6-thioguanine resistance) in normal FBL are low. These criteria may be useful for assessing environmental mutagen/carcinogen exposure in vivo. Assays of sister chromatid exchange frequencies do r.ot seem to be suitable for this purpose. (25 Refs) 127 AU - Lilts R AD - Environmental Sciences La.b., Ht. Sinai Sch. Medicine, New York, NY, 10029 TI - VINYL CHLORIDE AND POLYVINYL CHLORIDE EXPOSURE AND OCCUPAYIONAL LUNG DISEASE. SI - ICC3/61/07950 SO - Chest; 70(61:826-820 1900 LA - ENG AQ - Epidemiologic studies concerning the harmful effects of vinyl chloride (VC) and polyvinyl chloride (PVC) on humans are reviewed. The effects of VC or PVC on the respiratory system of exposed workers seem to indicate two patterns of nonmalignant effects: i) a granulomatous reaction To PVC dust with inclusion of PVC particles in macrophages and histiocytes and associated interstitial fibrosis; and 2) an interstitial pulmonary fibrosis caused by VC interacting with protein molecules and the immunologic mechanisms triggered bv the altered protein. Long-term effects include carcinogenicity. There is an increased incidence of lung cancer in exposed populations, and mice exposed to VC have developed hyperplastic changes of the alveolar lining cells and pulmonary tumors. An ultras truetural examination of these murine tumors seems To indicate that the tumors originated in type 2 alveolar cells. The magnitude of the carcinogenic effects of VC on humans has not yet been completely evaluated. (22 Refs ) 128 AU - Selikoff IJ AD - Environmental Sciences Lab., Mount Sinai Sch. Medicine, City Oniv. Nan York, 10 East 102 ST., New York, NY, 10029 TI - CHEMICAL DISEASE IN HUMANS: PP03LEM5 IN COMPARATIVE TOXICOLOGY. SI - ICC3/C1/07193 SO - Ciba Found Svmp; 76:331-367 1930 LA - ENG AB - Since the latent periods tor human tumors induced by such chemicals as vinyl chloride, Thcrotrast, beta-naphthy1 am 1ne , beneidine, and asbestos may be 20-30 vr, the carcinogenic potentials of more recently introduced v.enob i o t i cs (eg, polychlorinated biphenyls, poiybrominated biphenyls, or dioxin) cannot yet be determined. Xencbiotics may persist and accumulate 00005643 VINYL CHLORIDE PAGE 65 in tissue stores. Seme chemicals may seemingly disappear from the bodyi but leave a tissue imprint of their effects that appears decades after exposure ceases. Estimates of biologically active doses are sometimes complicated by the presence of highly toxic trace contaminants and homolcqs of ''prying biologic activities. The effects of chemical exposure on the tissues may be obscured by the absence of the characteristic symptoms normally associated with the disease. The lack of coherence between laboratory results and The clinical effects of engyme-inducinq agsnts may be explained by interactions between two or more xsnobiotics or between the chemicalts) and genetic or metabolic variables. Since there is much evidence that biologic processes are strikingly similar in different mammalian speciesi the toxicologic significance to humans of engyme induction and related processes requires careful evaluation. (22 Refs) 129 All - Wagoner JK ; Infante PF ; Aofeldorf RB AO - Environmental Defense Fundi Washington, DC TI - TOXICITY OF VINYL CHLORIDE AND POLYVINYL CHLORIDE AS SEEN THROUGH EPIDEMIOLOGIC OBSERVATIONS. 51 - ICDD/61/9559Q SO - J Toxicol Environ Health; 6(5/6):1101-1107 1930 LA - ENG AO * Epidemiologic evidence of The careinoqenici ty of vinyl chloride (VC) and polyvinyl chloride (PVC) is reviewed. Occupational exposure to VC has been associated with an increased risk of liver cancer. Cases of liver anqiosarccma have been reported in association with exposure to VC throughout the world. Apparent neoplastic changes in the livers of rats have been observed after the administration of VC monomers (as PVC powder in the diet) at levels of 3 and 9 nq/Kq body wt. Both experimental bicassav and epidemiologic study have demonstrated that the brain is a target organ for the carcinogenicity of VC. Evidence supporting the association of VC exposure and pneumoconiosis 13 presented. Studies are reviewed which suggest that the excess lung cancer risk in the VC-PVC industry is related to exposure to PVC dust, which is either a carrier of residual VC monomers or is itself a factor in the etiology of lung cancer. It is also possible that PVC dust particles in the lung slowly release VC monomer to small adjacent areas of the tissue, thereby prolonging contact with the chemical. More data are needed to demonstrate an association between VC and cancers of the lymphatic system. (23 Refs) 130 AU - Axelscn 0 AO - Dept. Occupational Medicine, Uni''. Hosp., Linkopinq, Sweden TI - CHLORINATED HYDROCARBONS AND CANCER: EPIDEMIOLOGIC ASPECTS. SI - ICDB/31/95333 SO - J Toxicol Environ Health; 6(5/61:1245-1251 1930 LA - ENG A3 - Clinical and epidemiologic data on the carcinogenic properties of the more Important Halogenated hydrocarbons are reviewed. Mutagenic and carcinogenic prooerties have been reoorted for pesticides such as lindane, chlordane, phenoxy acids, and various ( L,, c c r-.*'-, * 00005644 VINYL CHLORIDE PAGE 66 chlorophenols. Chlorinated solvents !CC14j trichioroethyiene, methyichloroform , and methyl chloride) hawe been shown to be carcinogenic in animals, but similar epidemiologic evidence is limited. Both chloromethyl methyl ether and bischloromethyl ether are potent cancer initiators in animals. Vinyl chloride has been mentioned as a probable cause of liver angiosarcoma in exposed workers and may be the cause of other cancers. An excess of reticuloendothelial and lymphoid malignancies has been reported among anesthesiologists. The occurrence of trihalomethanes in drinking water has been associated with increased cancer in the general population including bladder cancer, brain tumors, kidney cancers, and non-Hodgkin's lymphomas. There is an urgent need for adequately designed epidemiologic studies. While bacterial test systems and animal experiments demonstrate the mutagenic and carcinogenic properties of these substances, few have bean conclusively associated with human cancer. (62 Refs) 131 AU - Bogovski P AD - Inst, Experimental and Clinical Medicine, Ministry Health Estonian SDR, Tallinn, USSR TI - HISTORICAL PERSPECTIVES OF OCCUPATIONAL CANCER. SI - ICDB/81/95320 SO - J Toxicol Environ Health; 6(5/6)1921-039 19S0 LA - EMS AB - The present state and possible future trends of occupational cancer, some lessons from the past, and the potential incut from experimental research are reviewed. The most important occupational carcinogens are asbestos and vinyl chloride. The problems of N-nitroso compounds (approx 30k of which have induced cancer in various species and organs) are discussed. In addition To the main cancer site associated with an occupational carcinogen, cancers at other sites appear more frequently. The controversy over the proportion of cancers related to occupation in the overall cancer incidence is discussed. Epidemioloqical studies, the proper functioning of health services, and prevention, all depend on adequate registration of cancer cases. Skin cancer caused by oil is reviewed in detail. Experimental data should be accepted as sufficient to warrant beqinnmq preventive measures. The multifactor i al etiology of occupational cancers is discussed. Experimental cancer research is discussed with respect to life-style and modifying factors acting on the penetration of a carcinogen into Target cells. Future Tasks and goals are discussed, (95 Refs) 132 AU AD TI SI SO LA AB National Toxicology Program - U. S. Public Health Service, Washington, DC FIRST At;!(UAL REPORT CM CARCINOGENS (JULY 1980). IC0B/C1/94530 First Annual Report on Carcinogens (July 1980). Bethesda, MD, Department of Health and Human Services, Vol. 1, 150 pp., 1980. ENG This report, from the National Toxicology Program, discusses a group of 26 lARC-reviewed chemicals and industrial processes R&S 139046 000056A5 VINYL CHLORIDE PAGE 67 initially found associated with the induction of human cancer. Data are included on exposure environment31 and The status of existing regulations of These chemicals. The group includes: aflatoxin, A-aminobiphenyl, arsenic and inorganic arsenic compoundsj asbestos, auramine, benzene. benzidine. N.N-bist 2-chloroethyl )-2-naphthylamine. bis t chloromethy1 lether, cadmium and cadmium compounds, chloramphenicol> chloromethyl methyl ether, chromium end chromium compounds, cyclophosphamide, di ethyls t i l'oestrol. hematite and iron oxides, isopropyl oils, melphalan, mustard gas. 2-naphthylamine. nickel and nickel compounds . oxymetholone. phenacetin. phenytoin and phenytoin sodium, soots, tars. oils, and vinyl chloride, (no Refs) 133 AU - Hong CB ; Winston JM ; Lee CC AD - Midwest Res. Inst.. Kansas City. MO TI - ANIMAL MODEL: ANGIOSARCOMA OF RATS AND MICE INDUCED BY VINYL CHLORIDE. SI - ICD3/S1/9A56A SO - Am J Pathol; 101(3):737-7A0 1930 LA - ENG A6 - Hepatic angiosarcoma may develop in humans exposed to vinyl chloride (VC). Thorotrast. and arsenic. In man. liver is the only organ affected by VC. Hepatocellular carcinoma is The only Tumor besides hepatic angiosarcoma suspected to be associated with VC exposure. The animal model for the studv of angiosarcoma in man adds another reproducible system to the study of tumor 1 genesis. treatment, and prevention of neoplasms. (10 Refs) 13A AU - Sharma RP I Yakel HO ; Gehrinq PJ AD - Dept. Animal. Dairy, and Veterinary Sciences, Utah State Univ., UMC 561 Logan, Utah, 3A322 TI - IMNUNOTOXICOLOGIC STUDIES WITH VINYL CHLORIDE IN RABBITS AND MICE, SI - ICDS/81/9A297 SO - Int J Immuncpharmacol ; 2(A)-'295-299 1980 LA - ENG AB - Immunologic responses to inoculated antigens were studied in rabbits exposed to vinyl chloride (VC), and the effects of two knoun major metabolites of VC mere observed in vitro in mouse splenic cells. New Zealand rabbits were exposed to 0 (control). 10. 100, or 1.000 ppm VC. 6 hr/day> 5 days/uk, for 8 wk in inhalation chambers. After A wk of exposure, the animals we-e injected in the footpads with an antigen containing a 1:1 mixture of tetanus toxoid and Freund's complete adjuvant; the injection was repeated 2 wk later. No effect of This treatment was noted when the body ut and wt of various organs (kidneys, brain, heart, Spleen, adrenals, and popliteal lymph nodes) of treated and Control rabbits were compared; hcwe''er, thymus wt showed a dose-related increase in rabbits treated with the Two highest doses of VC. Various tests of ant 1 gen-induced 'immune responses in VC-exposed rabbits revealed no treatment-related effects. Tre meorperation of jH-thym'dlne in splenic lymphocyte cultures of immunised and VC-exposed rabbits was very high, even in the absence of mitogens; this finding was consistent with that (" c c V 00005646 VINYL CHIOSIDE c PAGE 68 generally observed in Immunised animals. Exposure to 10 or 100 ppm VC further increased this spontaneous trans format i on, while exposure to 1,000 ppm VC produced a decrease. Incubation of mouse splenic lymphocyte cultures in the presence of Thiodiglycolic acid (TDGA) or N-acetyl-S-lhydroxyethyl)-eysteine did not suggest a definite effect. In contrast, when TOGA was given to mice in their drinKing water, there was a dose-related increase in the splenic lymphocyte transformations. (10 Refs) 135 AU - Cohen LF J Euig RA i Kohn KW ; Giaubiger 0 AO - Pediatric Oncology Branch, Div. Cancer Treatment, NCI, NIH, Bethesda, MO, 20005 TI - INTERSTRAND DMA CROSSLINKING BY 4,5',8-TRIMETHYLPSORALEN PLUS MONOCHROMATIC ULTRAVIOLET LIGHT. STUDIES BY ALKALINE ELUTION IN MOUSE L1210 LEUKEMIA CELLS. SI - 1CDB/81/94260 SO - Biochi in Biephys Acta; 610(11:56-63 1930 LA - ENG AB - DMA crosslinking by 4,5',8-tr imethylpsoralen plus monochromatic UV light of wavelength 365 nm was studied in mouse L1210 leukemia cells, DNA breaks and crosslinking were evaluated by alkaline elution of DNA from polyivinyl chloride) filters. Trimethylpsoralen plus 365 nm light produced ONA Crosslinks but not breaks. The kinetics of crosslinking were linear with respect to concentration and second-order with respect to light exposure time. The latter finding supports the proposed two photon mechanism for the formation of diadducts. In contrast to DNA crosslinking agents such as nitrogen mustard, nitrosoureas and platinums, trimethylpsoralen crosslinks were resistant to proteolytic digestion. Thus, trimsfhylpsoraien plus 365 nm light produced interstrand crosslinks, as proposed for a bifunctional agent binding to bases on opposite DNA strands. (Author abstract) 129 Refs ) 136 AU - Smith AH i Waxweiler RJ ; Tyroler HA AD - Dept. Community Health, Wellington Clinical Sch. Medicine, Wellington Hosp., Wellington 2, Mew Zealand TI - EPIDEMIGLOGIC INVESTIGATION OF OCCUPATIONAL CARCINOGENESIS USING A SERIALLY ADDITIVE EXPECTED DOSE MODEL. SI - ICDQ/81/94125 SO - Am J Epidemiol; 112(61:737-797 1980 LA - ENG AB - The epidemiologic identification of occupational carcinogens is cciip 1 j ca t ed by several problems including worker mobility between ]obs, variation over time of chemicals and processes used, and the long latency period between exposure and discovery of a tumor. In The light of these problems, a method uslnq the cumulative dose concept has been developed which involves calculating the expected yearly exposure for each case from work histories of all nonoases close to the case in yr of birth and yr of hire. The data required for use of The method include information concerning exposure to the chemicals being studied for each job in each calendar yr of the study. Use of the method R&S 139047 c r c c c ( *- *V ' * C 'v ( ( ! lAr '--'v ut, '.J 00005647 VINYL CHLORIDE c PAGE 69 is illustrated with a study of angiosarcoma of the liver 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, including exposure level relationships! latency information! and the possibility that two chemicals might be acting independently or jointly. The serially additive expected dose model is likely to prove particularly useful in the analysis of data collected by occupational health surveillance systemsi as well as retrospective studies of the type illustrated. (Author abstract) (18 Refs ) c c 33 CO 137 AU - Ressner P I Sram RJ ; Novakova J ; Lambl V AD - Inst. Hygiene and Epidemiology! 100 42 Praguei Czechoslovakia TI - CYTOGENETIC ANALYSIS IN WORKERS OCCUPATIONALLY EXPOSED TO VINYL CHLORIDE. SI - ICDB/31/93912 SO - Nutat Res! 73(21:425-427 1980 LA - EM3 AB - Chromosome analysis was done on lymphocytes obtained in 1977 and 1 yr later from 31 males (25-55 yr) exposed to 10 mg/cubic meter (m3) of vinyl chloride monomer (VCM) In air at the workplace! and compared with 35 controls not exposed to VCM. The analyses were done for four categories of chromosomal damage1 chromatid and chromosome breaksi and chromatid and chromosome exchanges. Calls carrying breaks and/or exchanges were classified as aberrant (AB). To compare intergreup differences the relative frequencies of AB and 95X confidence limits were calculated. The relative frequencies were compared using the Gaussian t test (t5X = 1,96). In all subjects! only breaks were detected. No significant differences were found either between VCM-exposed groups and matching controls (VCH-1977 vs control, t = 1.52; VCM-1973 vs control, t = 0.25) or between the first and second sample collections (t = 1.33), These results showed that if the VCM concentration in the air of the workplace is kept less than 10 mg/m3, no increase should develop in tine number of chromosome aberrations detectable in peripheral lymphocytes of these VCM-exposed workers. (12 Refs) CO CO o 00 c c c 138 AU - Ebihara I ; Yoshizawa K AD - Div. Work Environment and Occupational Diseases, Inst, for Science of Labor, Tokyo, Japan TI - THREE CASES OF LUNG CANCER AMONG POLYVINYL CHLORIDE (PVC1 WORKERS. 31 - ICDB/01/91911 SO - Rodo Kagnku; 56(10>:577-585 1930 LA - JFH AB - Patient 1, a 47-yr-old man with a 27-yr history of workinq in a vinyl sheet factory, had complaints of general malaise accompanied with 40 C fever, vomiting, coughing, chest pain, and pain in the right shoulder blade. The patient had been smoking 15 C1qerettes/day for greater Than 20 yr. Chest x-rays showed atelectatic change, constrictive pul-^omtis, and a tumorous swelling of the right hilar area. The patient underwent surgical (_ L L 0000564a VINYL CHLORIDE PAGE 70 139 AU AO TI SI SO LA AB 140 AU AO TI SI SO LA AB resection of the tumor with a diagnosis of epidermoid cancer. Patient 21 a 50-yr-old man with an 8-yr history of working as a polyvinyl chloride and vinyl chloride monomer (VCM) plastlc3 caster and a 25-yr history of smoking 12 cigarettes/day. was found to have a tumorous shadow in the region of the heart and lateral pleura with x-ray examination. The patient died prior to treatment for an adenocarcinoma. Autopsy showed small dust maculae> dust decomposition around vessels and bronchioles, and slightly Thickened and fibrosed bronchiolar walls. Patient 3> a 47-yr-old man who worked as a plastics caster for 9 yr. had a history of smoking 10 cigarettes/day for 25 yr. The histological type of the tumor in Patient 3 was unknown. All three primary lung cancers were considered to be due to low grade occupational exposure to VCM and/or vinyl dichlorides. (37 Refs) Daudel R Uni versite Pierre et Marie Curie CONQUERING CANCER: PREVENTION AND TREATMENT. ICDB/81/91Q09 Rev Palais Decouverte; 8(80):4-37 1980 FRE The prevention of cancer, along with its etiology, diagnosis, and treatment are discussed. The importance of a balanced diet (80 g of fats. 100 g of proteins, and 300 g of carbohydrates for a total of 2.400 calories) and exercise in the prevention of cancer is emphasised. The carcinogenicity of certain foods and methods of food preparation (smoked fish and meat) are discussed. Geographic differences in cancer incidence as related to dietary habits are described. It is suggested that alcohol consumption predisposes a person to liver cancer. Abstinence from cigarette smoking was suggested in view of the correlation between smoking and bronchial and pulmonary cancer. Signs of aerodigesTive. urinary cancer, gynecological, and breast cancer are discussed. Breast self-examination is described. The relationship between sunbathing and skin cancer is discussed. Leukemia, lymphoma, and cancers of the bone and nervous system are discussed. The hereditary nature of cancer is considered. The development of neoplasms and their metastasis are discussed. Carcinogenic compounds. such as benzene, benzopyrene. and vinyl chloride, and their effect on DMA are discussed. The role of radiation, viruses and other agents in cancer production is described. Methods of cancer diagnosis are described. Cancer therapy includes surgery, chemotherapy, radlotherapy. and immunotherapy. (10 Refs) arms F (Anvers i Te Paris VI, Paris, France THE ROLE OF DIET IN THE PRODUCTION OF PRIMARY LIVER CANCER ANO CERTAIN OTHER HUMAN CANCERS. ICD3/81/91393 Re1' Palais Decouverte! 8(80): 33-51 1930 FRE Three important food agents hepstocarc1noqenic in humans are im/cotoxins. ni trosamlnes , and halogenic ethylenes. In geeg-aohic firStm wit' i'.pi ilwwiWyiEvw^ ,j`vy1 ( " ( c ( K. ( i 00005649 VINYL CHLORIDE PAGE 71 141 AU AO TI SI SO LA A3 142 AU AO TI SI SO LA AB areas where consumption of aflatoxin Bl-eontaminated food is high there is greater incidence of liver cancer. Other mycotoxins, such os sterigmaToeystines , iuteoskyrines , and cyclochierot ines , have been shown To be carcinogenic in animals. Mitrosomines. found in fish, meats, alcoholic beverages, and tobacco smoke, have been shown To be hepatocarcinoqenic in animals. The hepatccarcinogenicity of foods treated with nitrites, nitrates, or gluconodeltalactcnes is discussed. The formation of The nitrosamines in The human gastrointestinal Tract is discussed. The hepaTocarcinogeniciTy of halogenic ethyienes, especially vinyl chloride, is discussed. Workers exposed To vinyl chloride have been shown to develop liver angiosarcomas. The hepatocarcinogeniciTy of natural substances (pyrroli2idine alkaloids), environmental pollutants (DOT, polychlorinated biphenyls, chloroform), food dyes, and other agents (amltrol, diallate, bist2-chlorethyl )etner , dimethoxan, and dioxan) is discussed. The role of polycyclic hydrocarbons in smoked meat and other foods in The production of digestive cancer is discussed. Pharyngeal and esophageal neoplasms are discussed in relation To alcohol intake and Tobacco smoking. The role of dietary fats in colon, breast, and prostate cancer is discussed, (no Refs) Harrison EA Natl. Technical Information Service, Springfield, VA TOXICITY CF VINYL CHLORIDE. CITATIONS FROM THE NTIS DATA BASE. ICCB/S1/91355 Aerosp Med Biol; (211):215 i<?so ENG Research is cited on the health hazards from exposure to vinyl chloride and vinyl chloride resins. Studies are included on The epidemiology of industrial and public exposures to the compound and its degradation and combustion products. This updated bibliography contains 90 abstracts, 0 of which are new entries to the previous edition. (Author abstract) (no Refs) Daune M ; Fuchs PP Departement da Biophysique, Universita Louis Pasteur, Strasbourg, France CHEMICAL CARCINOGENESIS. ICDB/fll/91051 Recherche; 11(1151:1066-1077 1930 FRE The chemical causes of cancer are reviewed. The historical significance of scrotal cancer in chimney sweeps IS discussed. The list of known chemical carcinogens includes polvcycllc hydrocarbons, bencene> and vinyl chloride, Chemical carcinogens affect the DMA of the cell by lysing the double strands and by causing modifications In the genetic information. These modifications lead to a decreased stability In the DMA molecules and to constraints which force the unwinding of the double helix such that there are resulting denatured cones. Chemical carcinogens are capable of causmq direct and indirect mutations. In order for cancer to develoo, the first initiation stage must 00005650 VIMTU CHLORIDE PAGE 72 be followed by a promotion stags. (9 Refs) 143 AU - Krajewski J ; nilczarska A ; Dobecki M AO - Zaklad Chemicznycn Zanieczyszczen Powietrza, Instytut Medyeyny Pracy, ul. Taresy 8, 90-9501 Poland TI - USEFULNESS Or DIFFERENT METHODS OF AIR SAMPLING FOR THE EVALUATION OF WORKERS' OCCUPATIONAL EXPOSURE TO VINYL CHLORIDE. SI - ICD3/31/90S45 SO - Med Pr; 31(3):165-170 1930 LA - POL AB - The vinyl chloride (VC) eoncentrations were measured in a polymerization plant by different sampling methods (stationary sampling, FIOAS autoanalyzer, and individual sampling) *0 determine the exposure of the workers. The findings showed that the uorker'3 exposure was estimated correctly only by air sampling in the breathing zone. The VC concentrations in the breathinq zone were in the range of 1.8-209.5 mg/cubic meter. (7 Refs ) 144 AU - Maclure KM ; MacMahon B AO - Dept. Epidemiology, Harvard Sch, Public Health, 677 Huntington \ve., Boston, MA, 02115 TI - AM EPIDEMIOLOGIC PERSPECTIVE OF ENVIRONMENTAL CARCINOGENESIS. SI IC0B/81/90393 SO Epidemiol Rev (Engl Transl Przegl Epidemiol); 2:19-48 1930 LA ENG AB Current epidemiologic knowledge concerning the relationship between environmental agents and cancer is reviewed. Different uses of the word 'environment' are discussed, and problems that arise from the failure to appreciate these different uses are outlined. Environmental agents here include two classes: substances to which exposure is deliberate (consumables) and substances to which exposure is inadvertent (contaminants). Epidemiologic evidence for associations between cancer and consumables is discussed for: Tobacco, alcohol, food (including fiber, fat, vegetables, essential nutrients, and nonnutrients such as coffee), drugs, and cosmetics. Epidemiologic evidence for associations between cancer and the following types of contaminants Is summarized: contaminants in The workplace, including asbestos, metal compounds , vinyl chloride, alkylating agents, etc; pollutants in The air, water, and food outside the workplace! bioloqlc contaminants, including viruses and mycotoxlns I and physical contaminants, including UV and ionizing radiation. Some of the problems encountered in quantitation of environmenta 1 carcinogens are examined; emphasis IS placed on problems of measuring dose, assessing response, determining latent period, identifying dose-response patterns, and considering the possible existence of threshold values and interactions between agents, (231 Refs) 00005651 VINYL CHLORIDE PAGE 73 145 AU AD TI SI SO LA A3 146 AU AD TI SI SO LA AB 147 AU AD TI SI SO LA AB Ottenualder H ; Bolt HM (c/o Bolt) Pharmakologisches InstituT, Dusseldorf University. Cbere Zahlbacher Str. 53. D-5600 Main;, U. Germany NSTA50LIC ACTIVATION CF VINYL CHLORIDE AND VINYL BROMIDE BY ISOLATED HEPATOCYTES AND HEPATIC SINUSOIDAL CELLS. ICDB/S1/9C103 J Environ Pathol Toxicol; 4(1):411-417 1930 ENG Hepatocytes and sinusoidal ceils were prepared from female Wistar rat 1iv=r, then separately incubated with 14C-iabeled vinyl chloride (VC) or its analog, "lnyl bromide (VB), to study the oxidative metabolism of vinyl chloride in The liver. Metabolic activation in each incubation was measured by determining the extent of covalent binding of metabolites to protein. The capability of sinusoidal cells to transform VC and VB to protein alkylating metabolites was less than that of hepatocytes, and was not detectable in some experiments. A lower alkylation rate of VB metabolites Was also shown. The results showed that VC and V3 are primarily metabolized within hepatocytes in rats. (13 Refs) Lazar is AYa ; Schmujlowjeh SM I Kalmlkova TA V. A. Karqin Inst. Pclvn.er Chemistry and Technology, Dzerjinsk, Gorky District 606000, USSR DETERMINATION Or RESIDUAL VINYL CHLORIDE IN POLYtVINYL CHLORIDE) RESINS. IC03/31/89652 J Chromatogr; 193(3)1337-346 1930 ENG The determination of residual vinyl chloride (VC) in polyfvinyl chloride) (PVC) powders based on thermal desorbtion in a carrier gas stream and trapping of the VC is described. A trap is installed in the heated injection port of a gas chromatograph and desorbed volatiles are chromatcqraphad by a two-stage chromatographic svsTem. Nhlle VC is purged through an analytical column, the first column is cleaned by back-flushinq. The method has been tested on various types of PVC powders and has no limit of sensitivity. (Author abstract) (31 Refs) Rogan WJ Biometry Branch, Natl. Inst. Environmental Health Sciences, P. 0. Box 12233, Research Triangle Park, NC. 27709 THE SOURCES AND ROUTES OF CHILDHOOD CHEMICAL EXPOSURES. tCDB/Sl/09468 J Padiatr ; 97(51:361-065 1980 ENG Exposure conditions examined include: toxic chemicals carried home by parents returning from work, exposure of mother and fetus to toxic chemicals at the mother's place of employment, air pollution hazards , concentraiicns of Toxic chemicals in mothers' milk, bioaccumulat1 on of chemicals in lower stages of the food chain which in Turn are ingested by humans, accumulation of chemicals in various parts of The human body, pollution in the c c c .-rS -'yv; ' : .y-yy.y.vJl-.-Xye'/.* y ;y 33 ft cn CO <0 o CJI co 00005652 VINYL CHLORIDE c PAGE 74 home particularly arising from renovations or inappropriata use of chemicals; and exposures of epidemic proportions resulting from accidental spillages, massive misuses of chemicals, or improper storage of chemical wastes. Specific references to cancer included the development of mesothelioma in children who had been playing in mine tailings around asbestos sites, the development of angiosarcoma following vinyl chloride exposure, and lung cancer in response to toxic irritants. (49 Refs) 148 AU - Boccelli JU ; Kerbekus 6B AD - Air Pollution Res. Lab.. New Jersey Inst. Technology. Newark. NJ TI - ANALYSIS CF SELECTED VOLATILE ORGANIC SUBSTANCES IN AMBIENT AIR. SI - ICD3/S1/B3320 SO - Analysis of Selected Volatile Organic Substances in Ambient Air. Available from National Technical Information Service. Springfield, Va,, as PB80-144694:, NS0-26960, NJDEP-79/02. HC AQ5/HF A01 CSCL 07D, 80 pp., 1930. LA - ENG AB - Sampling/analytical methodologies and laboratory techniques in determining the concentrations of selected volatile organic substances in the vapor phase are described. A total of 330 samples from northern New Jersey were collected. The samples ware Then analysed for fcencene. carbon tetrachloride. chloroform, o-dichlorcbengene and p-dichlorcbengene . 1>2-dichloroethane, nitrobengene> t etrachloreethylene. 1.1.1-trichloroethane, trichloroethylene. and vinyl chloride. Full data sets for all samples are appended to the report. (Author abstract) 149 AU - Moore EC AD - No affiliation given TI - WOMEN ANO HEALTH ISSUES: OTHER HEALTH CONCERNS, SI - ICD3/S1/3S214 SO - Public Health Rep; 95< Suppl )' 33-47 1930 LA - ENG AB - Environmental, occupational, and cultural conditions associated with carcinoqen exposure among women are reviewed. More than 90X of all hairdressers and beauticians are women, and many aerosol sprays used by such workers in the past have contained vinyl chloride, a liver carcinogen. Many hair dyes have been shown to be mutagenic. Nomen comprise 56X of the textile worker population, and exnosure to asbestos-contalninq textile products may lead To the development of lunq and other types of cancer. Nomen account for almost two-thirds of the workers in the laundry and dry cleaning industry, and dry cleaning workers are exposed to solvents such as cerchloroethy 1-ne, which has been linked To cancer in animaL studies. Cultural habits associated with carcinogen exposure among women include increased cigarette Smoking and the use of cosmetics. (45 Refs) c c c c c ( c L C L L- V 00005653 VINYL CHLORIDE PAGE 75 150 AU - Baxter PJ ; Anthony PP ; Macsween RN i Scheuer PJ AD - Employment Medical Advisory Sarvlcei London N'.-ll 5DTi England TI - ANGIOSARCOMA OF THE LIVER: ANNUAL OCCURRENCE AND AETIOLOGY IN GREAT BRITAIN. SI - ICBB/81/874A2 SO - Br J Ind Med; 3713):213-221 19S0 LA - ENG AB - The annual occurrence of angiosarcoma of the liver (ASL) in Britain from 1963 to 1977 was studied, including clinical and occupational details for those cases agreed as ASL by a panel of histopathologists. Thirty-five cases (28 men, 6 women, and 1 infant girl) were agreed as ASL. The increase in the incidence of ASL observed in recent yr was attributable to Thorotrast (thorium dioxide) usage (8 cases) and exposure to vinyl chloride (2 eases) in the past. In its clinical presentation and prognosis ASL resembled primary liver carcinoma, except that extrahepatic metastases were found in only eight (23X) cases, and hemoperitoneum was more common in those cases due to Thorotrast. The results suggested 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 one case were indicative of arsenical intoxication, but medications in the other patients did not appear to be of etiological importance. (Author abstract) (32 Refs). 151 AU - Harrison EA AD - Natl. Technical Information Service, Springfield, VA TI - TOXICITY OF VINYL CHLORIDE (CITATIONS FROM'THE NTIS DATA BASE). SI - ICDB/81/07218 SO - Toxicity of Vinyl Chloride (Citations from the NTIS Data Base). Available Through National Technical Information Service, Springfield, Va,, as FB80-807662:, P380-807662, 97pp., 1930. LA - ENG A3 - Research is cited on the health hazards from exposure to vinyl chloride and vinyl chloride resins. Studies are included on the epidemiology of industrial and public exposures To the compound and its degradation and combustion products. (This updated bibliography contains 90 abstracts, 8 of which are new entries to the previous edition). (Author abstract) 152 AU - Belanqer PL i Elosh E AO - ilacard Evaluations and Technical Assistance, Natl. Inst. Occupational Safety and Health, Cincinnati, CM TI - HAZARD EVALUATION AND TECHNICAL ASSISTANCE. REPORT NO. HE 78-73-612, KENTILE FLOORS, INC., CHICAGO, ILLINOIS. SI - ICDB/01/87172 SO - Haqard Evaluation and Technical Assistance. Report No, HE 73-73-612, Kentile Floors, Inc., Chicago. Illrnois. Available from National Technical Information Service, Springfield, Va,, as F330-16109A , NI0SH-TR-HHE-73-73-612, 26 pp., 1930. LA - ENG r &S 139055 00005654 VINYL CHLORIDE PAGE 76 AB - An environment and medical survey was conducted on June 26 and 27t and August 19 to 22, 1976 at Kentile Floors, Incorporated, Chicagoi Illinois at the request of an authorized employee represent ative to determine the potential exposure of 50 employees to asbestos (1332214), polynuclear aromatic hydrocarbons> vinyl chloride monomer (75014), talc (14807966), alpha methyl styrene (98S39), and numerous organic and Inorganic dyes and pigments used in the production of vinyl asbestos and asphalt asbestos floor coverings. None of the test chemicals exceeded the CSHA recommended criteria, and no cases of asbestosis or other occupationally related disease were documented among the past or present workers. The investigators recommend that the company review their material inventory for potentially toxic chemicals and periodically monitor these chemicals and that employees be instructed on proper respirator use and other safety precautions. A canopy exhaust system should be installed, carcinogenic chemicals should be identified and stored separately from noncarcincgens, the ventilation exhaust systems should be inspected periodically , and workers potentially exposed to asbestos should change clothes and shower before leaving the workplace. (Author abstract) 153 AU AD TI SI SO LA AB Anderson D I Richardson CR ; Weight Tit 1 Purchase IF ; Adams MG Central Toxicology Lab., Imperial Chemical Industries Ltd., Aldsrley Park, Macclesfield, Ches. SK10 4TJ, England CHROMOSOMAL ANALYSES IN VINYL CHLCRI0E EXPOSED WORKERS. RESULTS FROM ANALYSIS 17 AND 42 MONTHS AFTER AN INITIAL SAMPLING. ICD3/S1/S6316 Mutat Res; 79(2 ):151-162 1900 ENG The second and third blood samplings were taken from workers occupationally exposed to either vinyl chloride or polyvinyl chlcride, and the incidences of chromosomal aberrations were compared to the previously reported results of the first sampling. The second and third samplings were taken 13 and 42 mo, respectively, after the first sampling. Threshold limit values for vinyl chloride and plant exposure were reduced after the first sampling. The second sampling showed that there was a tendency toward increased chromosomal abnormalities in the "inyl chloride-exposed workers. Workers who had moved away from polyvinyl chloride production had significant decreases in some types of chromosomal damage, compared to the trend for all workers. In the third sampling there was a tendency toward a decrease in the percentage of cells with chromosomal aberrations of various types, compared to both previous samplings. It was concluded that reduction in exposure to vinyl chloride is accompanied by a reduction in the chromosomal abnormalities to levels indistinguishable from these of controls. (13 Refs) r. c c (' (. t. 00005655 VINYL CHLORIDE PAGE 77 1S4 AU - Walsh CT AD - Dept. Chemistry and Biology! Massachusetts Inst. Technology! Cambridge! MAi 02139 TI - SCOPE AND MECHANISM OF ENZYMATIC NONCOXYGENATICN REACTIONS. SI - ICD8/S0/S5295 SO - Anno Rep Med Cneml 15:207-216 1960 LA - ENG AB - The role of the iron-i coppei--i flavin-i and pteridine-dependent monooxygenases are discussed. In liver metabolism, and to a lesser extent in lung and intestine, PASO monooxygenases are used as the main apparatus for drug metabolism and detoxification of other xenobiotics by sequences that introduce hydroxyl functionality to increase polarity and so facilitate aqueous solubility and urinary excretion. Exposure of a mammal to a uide variety of xenobiotics (egi pnenobarbitai, 3-methyicholanthrene) induces high levels tup to 107. of the protein of liver cell endoplasmic reticulum) of a family of P450 isocymes. The detoxification process, however, occasionally leads to the generation of toxic products. The interaction of P450 with nitrcsamines , bencota Ipyrene , vinyl chloride, or thiccarbamate herbicides can form biologically harmful products. Darvon can titrate out P450 drug metabolism caoacity, chanqing pharmacokinetic disposition of other drugs and generating profound pharmacological alterations, (66 Refs) 155 AU - Thiess AM ; Frentrel-Beyme R ; Link R ; Wild H AD - Arbeitsmedipin une Gssundheitsschutc, BASF Aktiengesellschaft, 6700 Ludwigshafen, W. Germany TI - MORTALITY STUDY OF CHEMICAL INDUSTRY WORKERS IN VARIOUS ESTABLISHMENTS WHO MERE ALSO EXPOSED TO ACRYLONITRILE. SI - ICDB/80/B4521 SO - Zentralbl Arbeitsmed Arbeitsschutp Prophyl; 30(71:259-267 I960 LA - GER AB - A mortality study of 1,469 chemical industry workers exposed to acrylonitrile (AN) and to various other organic substances (including vinyl chloride, ethyl benpoi, acrylamide, nitrobenpol, and phenol) is described. There were 89 deaths among these workers employed in 12 West German plants before May 15, 1973. Based on the population of West Germany, 99 deaths would ha-'e been expected. Twenty-seven of the observed deaths were due to malignant neoplasms, whereas only 20.7 such deaths would have been expected; the difference is not statistically siqnificant, however. The ratios of observed to expected deaths were 11:5.6 for lung carcinomas and 4:1.7 for neoplasms of the lymph nodes and hematopoietic tissues! these differences are statistically significant. Deaths due to natural causes were equal to or below the expected number, but there were nine suicides (5.2 expected). Because of the multiple exposures, a specific AN-reietsd career risk Is difficult to estimate. Eased on animal' experiments and other epidemiological studies, however, there are reasons to suspect that AN is carcinogenic. (13 Refs) DO * (/) gj CD O CJ1 ^1 r t '*' `*r* *>*T* "4 c ( L-^V-~U''-WV': -d:y.u-U-''';T-`! I 00005656 VINYL CHLORIDE c PAGE 78 156 AU - Wi sniewsko-Knypl JM ; Klimczak J ", Kolakowshi J AD - Oept. Biochemistry, Inst. Occupational Hedicine, Teresy 8, 90-950 Lodz, Poland TI - MONOOXYGEHASE ACTIVITY AND ULTRASTRUCTURAL CHANGES OF LIVER IN THE COURSE OF CHROMIC EXPOSURE OF RATS TO VINYL CHLORIDE. SI - ICDS/SO/33351 SO - Int Arch Cccup Environ Health; 96( 3) ' 291-299 1930 LA - ENG AB - The effect of long-term repeated exposure of Wistar rats to vinyl chloride (VC'- 50 500, and 20,000 ppm) on the activity of cytochrome P-950 monooxygenase (MOA ) and the ul tras true ture of the liver uas investigated. The rats were exposed for 5 nr/day, 5 days/uk for io mo. Measurements uere performed after 1, 3, 6, and 10 mo of exposure. After 1 and 3 mo of exposure to 500 and 20,000 ppm VC, the level of MOA was slightly lower than in Controls, and was restored to the original level upon continued exposure; a slight increase in The activity of aniline p-hydroxylase uas noted. The development of liver enlargement was accompanied by ultrastructural alterations beginning in the third mo of exposure at all concentrations. Hepatic alterations included hypertrophy of smooth and rough endoplasmic reticulum, swelling of the mitochondria, accumulation of lipid droplets, and focal cytoplasmic degradation. These changes are discussed with respect To the activity of The MOA system in metabolizing VC to Toxic metabolites. (23 Refs) 157 All AO TI SI SO LA A3 Darnis F Hospital Saint-Antoine, 75012 Paris, France ROLE OF DIETARY FACTORS IN THE ORIGIN OF PRIMARY LIVER CANCER. ICD3/80/3295I Gaz Med Fr) 87(22)12363-2866,2363,2370 1930 FRE Primary liver cancer is 100 times more frequenT in Senegal, northern Mali, Mozambique, and Zimbabwe than in western nations. This unequal distribution is not due to genetic or racial factors, since liver cancer is equally frequent among whites and blacks in the United States. The presence of certain substances in the human environment, especially in foods, helps to explain the disparity. Among the most important of these substances are mycotoxins, including aflatoxin, steriqmatocystine, luteosXyrme, cyclochlorotine; nitrosamines such as dlethyIniTrosamine , M-niTrosopyrrolidlne, ethylnitrosourea, and gluconodeltalactone I and halogenated ethylenes, mcludinq vinyl chloride, trichlorcethylenei and polyvinyl chloride. Althouqh many of these substances are released into the environment during manufacturing and combustion, There are also many which are natural products and Contaminate Improperly stored foods (aflatoxin) and drinking water supplies. Because human cancer is of mu!t1factorlal origin, the notion of a 'threshold dose' below which consumption is safe may be an illusion, (3 Pefs) c ( c c c l c c e e L L ( c c c. k ^4*fid l'~t- f. t. 00005657 VINYL CHLORIDE PAGE 79 153 AU - Krajewski J ; Dobecki M ; Milczarska A AD - Zaklad Chemi cznych Zan i eccyszczen, Instytut Medyeyny Pracy, ul. Teresy 8, 90-950 Lodzi Poland TI - EVALUATION OF THE WORKING ENVIRONMENT IN PVC PLANTS. SI - ICDB/60/32946 SO - Mad PrJ 31(2):1A9-153 1930 LA - POL AB - The atmospheric concentrations of vinyl chloride (VC) were measured during the first A yr of operation of a VC plant in Poland. The highest concentrations (253-1,330 mg/cubic meter) were measured during the cleaning of pressure vessels. It was possible to reduce the VC emissions considerably through technical measures. (7 Refs) c c 30 fio C/1 ' CO <> O tn oo 159 AU - Higginson J ) Coe JT J Lang RA AD - Lyon, France TI - REGULATING CARCINOGENS IN THE WORKPLACE (3 LETTERS TO EDITOR). SI - ICDB/80/S0753 SO - Technol Rev; e2<8):2,83 1930 LA - ENG A3 - Comments on Samuel Epstein's article 'Cancer, Inflation, and the Failure to Regulate' (December/January 1930, Technol Rev) are presented. One document cited in the article was incorrectly said to have been prepared by experts from the International Agency for Research on Cancer. Represent atives of industry reaffirm their positive contributions To and suggestions for researching and regulating the levels of carcinogens in the workplace. Examples of such carcinogens were acrylonitr i le and heavy vinyl chloride, (no Refs) 160 AU - Anderson MU ; Hoel DG Kaplan NL AD - Lab. Pharmacokinetics, Natl. Inst. Environmental Health Sciences, Research Triangle Park, NC, 27709 TI A GENERAL SCHEME FCR THE INCORPORATION OF FHARMACCKINETICS IN LON-OOSE RISK ESTIMATION FCR CHEMICAL CARCINOGENESIS: EXAMPLE VINYL CHLORIDE. SI ICD3/30/30030 SO Toxicol Appl Pharmacol; 55(1):15A-161 1930 LA Et.'G AB It is suggested that the fate of carcinogens is not always dose dependent but that covalent binding to DMA produces the genotoxic effect that is the initiating sweat of carelnogenes Is. A general scheme is proposed for low-dose extrapolation of care I noger.es 1 s , based on the DNA-carclnogen adduct formed. A pharmacokinetic model is presented, relating exposure concentrat1 on to the amount of DNA-carclnogen adduct formed. Two pharmacoklnetic models for vinyl chloride are presented. (12 Refs) c L C C L t-.r*.' "* V1",- c rf* " (. c c 0000565S VINYL CHLORIDE PAGE 60 161 AU - Pialat J > Pasquier B 5 Pa'nn H i Koop N AD - Lab. d'Anatomie Pathologique> C.H.L). da Lyoni Faculty Alexis Carrel1 rue Guillaume-Paradin, 69372 Lyon, Franca TI - HEPATIC LESIONS CAUSED BY VINYL CHLORIDE MONOMER (CVM). SI - ICDB/SO/79932 50 - Sam Hop Paris; 56(2S-2S ):11SS-1202 I960 LA - FRE AB - The history of discoveries concerning The carcinogenic character of vinyl chloride monomer (VCM) are reviewed and include The discovery of its mutagenic role, its carcinogenic effect cn humans and its relationship with hepatic fibroses. Case studies are presented for six hepatic angiosarcomas (IIA), one malignant hepatoma, and one fibrosis in patients chronically exposed to VCM. All patients were men (av age 51 yr) who uorked in industries with VCM for 10-30 yr. Hepatomegaly uas a common finding in HA cases, although all other clinical and histological findings were typical. Unlike other cases of hepatoma union have been secondarily reclassified as HA, the case in this series uas clearly a hepatoma. The case of fibrosis uas classified as isolated fibrosis secondary To VCM. (Ill Refs) 162 AU - HogsTedt C ; Uesterlund B AO - Orebre, Sweden TI - MORTALITY OF FOREST WORKERS EXPOSED AND UNEXPOSED TO PHENCXY ACID PREPARATIONS. 51 - IC0S/80/76947 SO - Lakartidningen; 77(19):1320-1031 1900 LA - SUE AB - Mortality and tumor incidence of 142 forest uorkers exposed To phenoxy acid preparations , 244 unexposed workers , and 16 foremen were investigated in an epidemiological study using payrolls from the 1950's and 1960's. The highly exposed foremen shoued significantly greater incidence of tumors compared with normal values taken from the cancer registry statistics. Occupational exposure to various phenoxy acid preparations , ie amitrol, 2,4,5-T ( 2,4,5-Tr i chloi'cphenoxyacet l c acid) and its derivative, TCCD (2,3,7,S-tetrachlorodibenoo-p-diox 1n), and 2,4-D ( 2,4-di chlorophenoxyr.ee 11 c acid) resulted in malignant soft-tissue tumors. These compounds are also teratogenic and mutagenic. Aerial spraying with 2,4,5-T was implicated in miscarriages in Oregon and chromosomal damage in Vietnam. Phenoxy preparations have been used in Sweden since the early 1950`s for control of vegetation. The subjects of the study were divided in three groups: exposed uorkers (more than 5 days exoosure). foremen (highest exposed), and unopposed. Many of the 142 Workers had also planted DDT-treated trees. The foremen had higher mortality and tumor deaths than normal (3 to 1), while Tumor deaths were lower than normal both among exposed and ungxQo^Bc! workers. With minimun 60 days exposure Tuiv.gr mortality increased and this trend became stronger with 120 days exposure. The higher Tumor deaths among the foremen might have been associated with their greater exposure to phenoxy acid c l c L L r &S 139059 00005659 VINYL CHLORIDE PAGE SI c preparations. It is conceivable that phenoxy acid preparations, just like vinyl chloride, increase the incidence of certain types c of tumors but that their overall careinogenicity is relatively low or moderate. (15 Refs) 163 AU Blejer HP c AD City of Hope Hosp.i City of Hope. CA TI IS YOUR PATIENT'S JC3 KILLING HIM? SI ICDB/80/76930 SO Ned Times; 108(71:91-95 1980 LA ENG AB Occupational carcinogenesis is discussed. The dangers of exposure to anesthetic gases, arsenic, asbestos, bencene, carbon disulfide, carbon tetrachlorida, coal, coke oven emission. DBCP, DDT, lead, mercury, talc, vinyl chloride, styrene, butadiene, (.' chromium, bis(chloromethyllether> uranium, chlorcmethyl methyl ether, chromates, nickel, soots and tars, isopropyl oils, wood dusts, cutting oil, 9-ami nobiphenvl, bencidine, c beta-naphthylamine, magenta, 9-nitrodi phenyl, auramine, chloroprene, cadmium, PCBs, beryllium, trichloroethylene, tetrachloroethylene, heptachlor, dieldrin, chloroform, and aldrin are presented in tabular form. (9 Refs) f. 169 AU Filser JG ; Bolt HM AD Abteilung fur Toxikoligie, Pharmakoloqisches Institut der Uni versitat Maine, Obere Zahlbacher Strasse 67, D-6500 Naina, W. Germany TI CHARACTERISTICS OF HALOETHYLEKE-INDUCED ACETONEMIA IN RATS. SI ICQQ/OO/76255 SO Arch Toxicol (Berl); 95(21:109-116 1900 LA ENG AB A series of haloqenated ethylenes (vinyl chloride, vinylidene fluoride, cis- and trans-l, 2-dichloroethylene> perchloroethylene) induces increased acetone exhalation in rats. Exposures of differently pretreated rats to vinylidene fluoride suggest that a metabolite of the haloethylene must be involved in eliciting this formation of acetone. This conclusion is based on la) dependence of acetone exhalation on the concentration of vinylidene fluoride, (b) effect of inducing agents, (c) effect of pyraool, a metabolic inhibitor, (d) effect of cysteine, (e) effect of hypoxia and (f) the time course of acetone exhalation. (Author abstract) (11 Refs) 165 AU AD TI SI SO LA AB Nunakata H ; Yosipaua Z Dept. Biochemistry, Tohoku Unlv. Sch, Medicine, 2-1, Selryo-machi , 5endsi 9G0, Japan ISOLATION AND CHARACTERIZATION OF A SULFATED GLYCOPROTEIN FROM A TRANSPLANT A3LE COLORECTAL ADENOCARCINOMA OF RATS. 1003/80/75722 Biochim Blophys Acta; 623(21:912-917 1930 ENG A Transplantable colorectal adenocarcinoma from rats of the ACI/N strain was extracted with 5 milliN E0TA (pH 7.0), and 00005660 VINYL CHLORIDE PAGE 82 166 AU AO TI SI SO LA AS 167 AU AD TI SI SO LA AO frac t lonated bv gel filtration on Sepharosa 63. followed by preparative polv(vinyl chloride) zona eiactrophoresis. An acidic glycoprotein (SGP) thus obtained was shown to ba homogeneous by electrophonesis on cellulose acetate membrane and on sodium dodacyl sulfate agarose cel. SGP contained 61.9/ carbohydrate. 23,9/ total amino acids and 1.6/ sulfate. The major monosaccharidas in SGP ware galactose, glucosamine and galactooamina. Small quantities of sialic acid. L-fucose and mannose were also present. Threonine, serine, prolina. glutamic acid and aspartic acid mere the major amino acids of the protein moiety. (Author abstract) (13 fiefs) Basler A ; Rohrborn G Institut fur Humangenetik und Anthrooologl e der Universitat. Uni versitatsstrasse 1. Gobaude 23.12, D-6000 Dusseldorf 1, U. Germany VIHYL CHLORIDE: AN EXAMPLE FOR EVALUATING MUTAGENIC EFFECTS IN MAMMALS IN VIVO AFTER EXPOSURE TO INHALATION. ICD3/80/73932 Arch Tokico! (Beri); 65(1):1-7 1930 ENG As part of a program of investigations on the mutagenic effects in mammals in vivo after inhalation of environmenlal chemicals, the effect of the industrial compound vinyl chloride (VC) was analyzed. Chinese hamsters were exposed to 1.25Z. 2.5X or 5/ (v/v) VC in air for 6. 12 or 26 hr. Bone marrow chromosomes were analyzed for induced chromosome aberrations and 3istsr-chromatid-exchsnges (SCEs) 26 hr after beginning of exposure. The frequency of VC-induced chromosome aberrations and SCEs both depend on dose and length of exposure- The highest measured effects were 33.25 SCEs/cell after an exposure to 2.5/ VC for 26 hr and 25.7/ metaphases with aberrations, when exposed to 5X VC for 26 hr. (Author abstract) (21 Refs) Buchtor A I Filser JG I Peter H I Bolt HM Institut und Poliklinik fur Arbeits- und SoziaimediZin, Universitat Koln, Josef-Stelzmann-STrasse 9. D-5000 Koln 61, W, Germany PHARMACOKINETICS OF VINYL CHLORIDE IN THE RHESUS MONKEY. ICD3/30/72553 Toxicol Lett! 6(1)133-36 1930 ENG The pharmacokinetics of vinyl chloride (VC) were assessed in Rhesus monkeys exposed to various air concentrations of VC in a closed s'stem. When the animals were e'-nosed to VC concentrations of up to 200 ppm. VC disappeared fro." the atmosphere according to a first-order law. The clearance was 3,55 liters/hr/kq body wt. but could be decreased by 90/ after administration of the metabolic inhibitor d1sulf1ram. Uhen the absolute rates of VC metabolism were plotted against the VC exposure conesntrat1ons. first-order kinetics applied for The 200-300-ppm concentra11 on range. AT higher coecenlra*1ens. the plptted curve was nonlinear and showed saturation character 1st1cs. Based on the first-order c c c c c c c c c L L ca 00005661 VINYL CHLORIDE 33 (n 03 (O O 07 ro PAGE 33 c cmetabolic rates of VC in Rhesus monkevs, it is concluded that this species is a closer approxlmation to man than other animal c cmodels. For example, rats, mice, and gerbils metabolise VC 5-12x faster than humans. (6 Refs) 163 AU Padgett J AD Office Air Quality Planning and Standards, Environmental c cProtection Agency, Research Triangle Park, NC, 27711 TI POLICY AND PROCEDURES FCR IDENTIFYING, ASSESSING, AND REGULATING AIRBORNE SUBSTANCES POSING A RISK OF CANCER. SI ICDB/30/63139 SO Fed Regis I; 95(106):36937-36939,37116 1930 LA ENG ( AS The Environmental Protection Agency's proposed policy for controlling emissions of airborne carcinogens (eg, asbestos, c( vinyl chloride, and benzene) is reviewed. The policy is based on the application of the best available technology, In most cases, the emission standards will be in the form of performance Standards. Nhere applicable, generic standards will be used for (. (the control of fugitive emissions from industrial sources. The benefits of the standards, the sources affected, and related regulations and actions are summarised. (3 Refs) 169 AU AD TI SI SO LA AB Ginqell R Drunk G ; Leuschen T i Gold B Eppley Inst. Res. Cancer, Univ, Nebraska Medical Center, 92 and Dewey Ave., Omaha, HE, 63105 EVIDENCE FCR METABOLIC EFOXIOATION OF A DDT METABOLITE (MEETING ABSTRACT). IC03/00/6Z153 Proc Am Assoc Cancer Res I 211112 1930 ENG 1,1,1-trichloro-2-bis(p-chloropneny1 )ethane (DDT) is metabolised via the series of intermediates ODD, ODNU, ODNS, DDNU and ODOH to DDA (structures are given) which 13 excreted in the urine free and as conjugates. DDMU is a chloroolefin analogous to vinyl chloride which is metabolicallv activated to a carclnoqen bv epoxidation. We have performed studies to determine if DDMU is also metabolised via a chloroepoxide which would be highly reactive and might account for the careinogenicity of DDT and DDD in mice. Rearrangement of the hypothetical chloroepox1de would yield metabolites which could be further oxidised and excreted as either or both alphahydroxy-ODA (OH-DDA) or alphachloro-QDA (Cl-DDA). CH-DDA has been detected in the urine of mice qlven 500 mg/kg po DDNU (approx 17. dose), together with DDCH and DDA, whereas after ad.nini s tra 11 on of DONG, the next metabolic intermediate, only traces (less than 0.C5K) were recovered as CH-OCA. These results suggest That DDT is metabolised in vivo to so,i,e extent la a reactive chlorcepoxide which might be an ultimate carcinogenic metabolite, (no Refs) c c c c L L \ -* j, *^i v-.-1 .<- _i Av^V*'i f.v_i -vrvi* 9 C c ( c. ( . V-.I-wr-'V1 o</;P V 00005662 VINYL CHLORIDE PAGE 89 170 AU - Kraybill HE AD - NCI, Room 3C37, Landow Building, Bethesda, MO, 20205 TI - EVALUATION Or PU3LIC HEALTH ASPECTS CF CARCINOGENIC/MUTAGENIC BICHEFRACT03IES IN DRINKING UATER. SI - ICDB/80/61695 SO - Prev Mad; 9(21:212-218 I960 LA - ENG AC - Environmental Protection Agency monitoring systems have identified 699 biorefractories in United States water supplies. From an original list of 309 biorefractories in 1977, the NCI has identified and classified 23 carcinogens, 30 mutagens, and 11 promoters in drinking waTer. The carcinogens include: bencotaIpyrene, carbon tetrachlcrldo, chloroform, vinyl chloride, 1,9-dioxane , methyl iodide, DDE, DDT, chlordane, lindane, dielcrin, bengene> vinylidene chloride, heptacnlor, 1,1,2-trich1oroethane , 1,1,2-tricnloroethylane, bis(2-chloroethyl )ethen , simacine, tetrachloroethylene, heptachlor epoxide, acrylonitrile, aidrin, and butyl bromide. The results of 12 reported epidemiologic studies on drinking water indicate that the risk of cancer may be greater in the following situations: surface water greater than ground water, chlorinated water greater than nonchlorinated water, high levels of trlhalomethanes (THM) greater than low levels of THM, and water from highly polluted surface water such as the Mississippi greater than surface water from less polluted waters. These studies have also suggested some association between THM and an increased frequency of bladder cancer. However, the results do not establish causality, and estimates of increased or decreased risk are extremely crude since effects of other factors, such as cigarette smoking, have not been ascertained. (16 Refs) 171 AU AD TI SI SO LA AD - Upton AC - Dept. Environmental Medicine, New York Univ. Medical Center, New York, NY - FUTURE DIRECTIONS IN CANCER PREVENTION. - ICDB/OO/61195 - Prev Med; 9(2 ): 309-314 1930 - ENG The detection and cnaracterlcation of risk factors is discussed in relation to designing future programs of cancer prevention. Such risk factors include various lifestyle factors (eg, UV radiation exposure, tobacco, and alcohol), dietary factors (eg, aflatoxin, safrole, and bracken fern), drugs (eg, diethylstilbestrol and chlornaphanne ) , and occupational factors (eg, ionising radiation, vinyl chloride, and asbestos). Also relevant are various proneoplastic conditions predisposing to The development of cancer such as familial polyposis of the colon, xeroderma pigmentosum, Down's disease, Fanconi's anemia, atrophic gastritis, and leukoplakia. The success of future cancer prevention programs is discussed in Terms of The integration of a broad range of disciplines, Intensified efforts at professional and public education, and close coordination with allied health 30 CO 03 to o o> 4* r 33 00005663 VINYL CHLORIDE PAGE 85 c c (.. ^-t'"-'/'-';*'.;^ -'~: f!2?5:*'>2S and regulatory agencies. (20 Refs) 172 AU - Tompa A AO - Kiserleti Patologiai Osztaly, Orszagos Munka es Uzemegeszsegugyi Intezat, Budapesti Hungary TI - METHODS FOR THE IN VITRO STUDY OF THE EFFECTS OF CARCINOGENIC SU3STANCE5, SI - ICD3/80/60932 SO - Orv Hetill 121(7):555-561 1980 LA - HUN A3 - Methods for the in vitro study of the effects of carcinogenic substances are discussed with special regard to the Ames test. Substances found to be carcinogenic in humans include aflatoxins, A-aminebiphenyl> asbestos arsenic compoundst auraminei benzene> bis-chloromeThyl ether, benzidine, cadmium oxide, chloramphenicol, chloromethyl ether, chromium compounds, cyclophosphamide, diethylstilbestrol, isopropyl oil, melphalan. mustard gas, 2-naphthylamine, nickel compounds, N. N-bis-(2-chloroethyl )-2~naphthylamine, oxymethaione, fenitoine, soot, tar, and vinyl chloride. The Ames test can give false-positive and false-negative results for some compounds I eg, such non-carcinogenic substances as A-acetylaminofluorene, alpha-naphthylamine, Folpet P, benzol a ,e Ipyrenes , di benzol a ,h )-an thracene, glye i dol, 1,2-epoxvbu t ane , 5-ni tro-2-furami do.vi me , 1 C( -ni trofuryl i dene )-ami no) hydantoine, 5-nitro-2-furaci1ic acid, sodium nitrite, and sodium azide were found to be mutagenic in the Ames test. On the other hand, such carcinogens as 0-toluidine, auramine. carbon tetrachloride, chloroprena , dieldrin, thiourea, urethane, thioacetamide , acetamide, ethionine, saffrol, l-hydroxy-saffrol, cicasine, sodium phenobarbital, A-aminoantipyrene, amitrol, and 1,2-dime thylhydrazine , are ncn-mutagenic in the Ames' test. (A8 Refs ) 173 AU - Rauls R AD - No affiliation given TI - STUDIES UPDATE VINYL CHLORIDE HAZARDS. SI - ICDB/80/60010 SO - Chem Eng News; 58(1A):27-28 1980 LA - ENG AB - Various animal and epidemiological studies presented at a NIH conference on vinyl chloride (VC) and its possible hazards uere summarized in this brief report. Cesare Maltoni of the Istituto de Oncoloqia in Bologna, Italy, examined the effects of VC and a feu structurally similar compounds m mice, hamsters, and rats for a total of 3 million rodent days and concluded that VC uas a multipotent carcinogen in rodents. Liver anglosarcomas and other tumors uere found in animals treated by inhalation with as little as 10 cpm VC or ingestion of 0.3 mg VC/kg body wt. Peter Infante, Occupational Safety and Health Administration, summarized various human epidemiological studies which, Taken together, indicated a greater incidence of brain cancers than of li'<er cancers auoog workers exposed to VC. Tabershau-Cooper Associates conducted for c c c c c c c e 30 e </> co to o 09 C71 c ?1 00005666 VINYL CHLCRIDE PAGE 86 -^,^..v::> c C r f :''J<ys'::4r.-?>'. *- sit - / the Chemical Manufacturer's Association an extensive epidemiological stud'/ of 10,173 workers in 37 of 63 plants producing VC cr polyvinyl chloride (PVC). Workers with high VC exposure did not die earlier than in the control population nor were they more likely to die from cancer; however, cancers of the brain, CMS, digestive system arid respiratory system were more common in the VC workers. In several other studies it was shown that PVC particles could be picked up by the lungs of animals or man. Exposure to PVC dust caused some changes in lung x-rays and in lung functions. VC was shown to cause mutations in bacteria. The question of whether VC might pose a reproductive hazard was not conclusively answered, (no Refs) 176 AU - Dalrl P AD - Division* di Medicine Generaie 1, Ente Ospedaliero Generale Regionale 'S. Chiara', Trento, Italy TI - EPIDEMIOLOGY OF LUNG TUMORS. SI - ICDB/30/60007 50 - Minerva Med; 71(6):265-268 1930 LA - ITA A3 - Epidemiological data on lung cancer are presented. The incidence of lung cancer has been growing, especially in women, due to the increasing percentage of smoking women. The lung cancer mortality in the United States white peculation was 1.55/100,000 in men and 1.50/100,000 in women in 1923, vs 63.20/100,000 in men and 12.60/100,000 in women in I960, The carcinogenic factors include radioisotopes, 3,6-benzopyrene, 3,6,9,10-dibenzopyrene , asbestos (which causes bronchogenic carcinoma and mesoThelioma ), haloethars, nickel chromates, inorganic arsenic, hematite, vinyl chloride, and printing ink. Diseases involving immune disorders or i mmunodepression (scleroderma, sarcoidosis, pneumoconiosis) can predispose to lung cancer, which is manifested in increased lung cancer incidence among such patients. (6 Refs) 175 AU - Zuccato E ; Marcuccl F ; Muss mi E AD - Istituto di Ricerche Farmacologiche 'Mario Negri', Via Eritrea 62, 20157 Milan, Italy TI - THE ROLE OF RESPIRATION IN VINYL CHLORIDE MONOMER EXCRETION IN RATS. 51 - ICDD/80/53718 SO - Toxicol Lett; 5(3/6)1213-217 1930 LA - ENG A3 - The effect of respiratory activity on the kinetics of pulmonary excretion of vinyl chloride monomer (VCM) was studied. In the first experiment, VCM was Injected (1. 5, or 10 mg/kg aqueous soln, l'') into a femoral cannula of anesthetized male CD-CC35 rats that were breathing through a tracheal cannula connected to a pump operating at a fixed flow rate of 30 ml/mln (22 rasp 1ra11ens/min ). At I-min intervals after the VCM injection, expired air and blood samples were collected and analyzed for VCM. It was found that VCM ccncentratlons in the expired air and blood were proportional To the amount injected; VCM disappaarance Curves from the lungs and blood appeared to be linear at 1 mg/kg, c c c c c c c c L L L R&S 139066 n ( 00005665 VINYL CHLORIDE PAGE 87 c and biphasic at 5 and 10 mg/kg. In a second experiment> VCM was injected (5 mg/kg. iv) while the pump flow rates (pulmonary ( ventilation) were set at 19, 30. or 70 ml/min. The results showed that the VCM excretion rate was directly proportional to pulmonary ventilation. Ho significant difference was noted between VCM blood levels in the various conditions. In a Third experiment, in which respiration was stopped for 1 min and then ( continued at a flow of 30 ml/min, There was no decrease in blood VCM levels while respiration was stopped. The blood VCM levels of rats with respiratory-stop and rats with normal respiration uere si gnif i cantiy different. The results of these experiments showed that VCM is mainly eliminated through the lungs. Over 90/ of The VCM was exhaled in rat breath in 9 min after an iv VCM injection. (5 Refs ) ( 176 AU Doss M AD Abteilung fur Klinische Biochemie, Fachbereich Humanmedicin der Phi 1ipps-Universitat, Pilgrimstein 2. 0-3550 Marburg an der Lahn, c U. Germany TI PATHCBIOCHEHICAL TRANSITION! OF SECONDARY COFROPORPHYRINURIA TO CHRONIC HEPATIC PORPHYRIA IN HUMANS, SI ICD3/80/53093 SO Klin Wocnenschr; 5313 ):191-193 1930 ( LA ENG AB Secondary coproporphyrinurias can be observed in one third of all patients affected by liver damage, especially by alcohol liver syndromes. Potentially, every secondary coproporphyrinuria can turn into a chronic hepatic porphyria, which progresses along several biochemically detectable latent phases and which indicates clinical manifestation by cutaneous symptoms. Tuo requirements are necessary for the transition of a secondary coproporphyrinuria To a chronic hepatic porphyria: 1) Genetic disposition of an autosomal dominantly inherited defect in uroporphyrinogen decarboxylase, which only becomes Subclini cally or clinically relevant through alcohol or estrogens (also oral \ contracept1ves ) in connection uith liver damage I 2) A toxic inhibition of uroporphyrinogen decarboxylase in the liver caused by polyhalcgenated hydrocarbons, such as hexachlorcbenzene, polychlorinated and polybromlnated biphenyls, dioxins and probably also methyl and vinyl chloride In combination with a present liver damage or caused by one of these aqents. Experimental results, further, prove a direct negative effect of alcohol on The activity of uroporphyrinogen decarboxylase. In all liver conditions one should look out for porpnyrinuria, because it represents an important criterion for Toxic liver damage and early diagnosis of a chronic hepatic porphyria Is assessed by differentiaT1ng hepatic porphvrInurias (Author abstract) (27 Refs) 3) R=> (/> co CO o CD 'J (' 00005666 VINYL CHLORIDE c PAGE 68 (" 177 AU - Boorman GA i McConnell EE > Cockrell BY ; Drew RT ; Stone GA AU - Haseman JK ; Moore JA AD - NIH, Natl. Inst. Environmental Health Science, Resarch Triangle Park, NC, 27709 TI - THE COMPARATIVE EFFECTS OF AN ANIMALS AGE AT THE TIME OF EXPOSURE AND EXPOSURE DURATION ON VINYL CHLORIDE CARCINOGENESIS (MEETING ABSTRACT). SI - ICDB/00/SG151 SO - Fed Prod (3,parti 1 = 596 1980 LA - ENG AS - Vinyl chloride was used as a model compound to determine the effect of exposure duration and age of animal at time of exposure on tumor induction. Groups of 56 Golden Syrian hamsters, F399 rat, Swiss mice and B6C3F1 mice were exposed to 200 ppm or 100 ppm of vinyl chloride, respectively, for 6 hr a day, 5 days a wk according to the following regimens; 0-6, 0-12, 0-18, 0-29, 6-12, 6-18, 12-13, 12-29 and 18-29 mo and were compared to unexposed controls. Following exposure all animals were held until found moribund or dead at which time a complete necropsy examination was performed. Histopathological examination of hamsters revealed the following exposure related tumors: hemangiosarcomas (primary tumor usually in the skin), tumors of the nonglandular stomach and mammary tumors. In the rats, exposure related tumors included hemanglosarcomas (primary tumor usually in the liver), hepatocellular tumors and mammary tumors). Early exposure (0-6 mo following weaning) resulted in a similar tumor incidence as continuous exposure (0-29 mo following weaning) and 6 mo exposure early in life resulted in a higher tumor incidence when compared to animals exposed for a similar time period later in life, (no Refs ) 178 AU - da Meester C I Duverger-van Bogaert M ; Lambotte-Vanderpaer M AU - Roberfroid M ; Fencelet F Harcier M AD - Lab. Biotioxicology, Dniv. Louvain, Sch. Pharmacy, U.C.L.-73,69, B. 1200 Brussels, Belqlum TI - MUTAGENICITY OF VINYL CHLORIDE IN THE AMES TEST. POSSIBLE ARTIFACTS RELATED TO EXPERIMEMTAL CONDITIONS. SI - ICCB/80/59912 SO - Mutat Res; 77(2):175-179 1930 LA - ENG AB - To demonstrate that variations in experimental conditions Used to evaluate the mutagenicity of vinyl chloride monomer (VCM) in the Ames test could explain some discrepancies observed between previously reported results, four series of experiments were carried out under different conditions. The results showed that . VCM exerted direct mutagenic activity toward Salmonella Tvphimurium TA1530, and this was related to VCM concentration in the atmosphere. The mutagenicity of VCM was strongly enhanced in the presence of 59 mix. However, the mutation frequency for the bacteria was enhanced when plates containing either bacteria alone or 59 alone were co-incubated in an atmosphere of VCM; the mutation frequency was not enhanced when plates containing c c c c c c c e L k. .u -u c c c DO fio C/> co <a o CT) oo 00005667 VINYL CHLORIDE c PAGE 89 bacteria alone were incubated in an atmosphere of VCM, without the co-incubation of plates containing S9 alone. The increase in mutation frequency was more pronounced when the S9 mix was derived from Aroclor-treated mice. These results suggest that the observed enhancement of VCM mutagenicity is correlated with the formation, under the influence of S9 1iver-metabolizing enzymes, of mutagens such as the volatile intermediate compounds chloroethylene oxide and 2-chloracetaldehyde. Quantitative results could be affected by numerous experimental conditions; the quantity of volatile metabolites, the vol of the experimental chamber, the number of plates, and the composition of the plates. (6 Refs ) 179 AU - Koller LD AD - Veterinary Medicine, Univ. Idaho, Moscou, ID, 83843 TI - PUBLIC HEALTH RISKS OF ENVIRONMENTAL CONTAMINANTS: HEAVY METALS AND INDUSTRIAL CHEMICALS. SI - ICDB/aO/53793 SO - J Am Vet Med Assoc; 176(61:525-529 1980 LA - ENG AS - Hazards to human health which are presented by the heavy metals and by the industrial compounds lead, cadmium, methylmercury, polychlorinated biphenyls (FCCs 1, polybrominated blphenvls (PQSs ), chemical carcinogens, asbestos, and vinyl chloride are reviewed. Humans are exposed to lead from lead-base paints, dust and dirt, ambient air (burning of coal and leaded gasoline), and industry (lead ore smelter, data reproduction, ceramics, newsprint, plastics and illegally distilled liquor), affecting the nervous system and Kidneys. Cadmium is found in water, meats, grains, dairy products, pigments, plastics, stabilizers, alloys, batteries, cigarette smoKe, and electroplating materials, causing an iron-deficient 1 microcytic hypochromic anemia and reduced concentretions of Hb. Methylmercury is found in chloroalKali plants, industrial processes , paper-pulp industry limac ides, fossil fuels, and other sources, causing cerebral palsey-like disease m infants and loss of sensation and death in adults. PCQs aro found in electrical capacitors and transformers, heat transfer systems, plasticizer applications, hydraulic lubricants, and other sources, causing mild anemia and hypoproTeinemia. A specific case of evoosure of animals and humans to PBBs is described including a listing of numerous clinical signs and symptoms. Chemical carcinogenesis is briefly considered. Asbestos 13 found in such sources as mlninq and manufacture of insulation, fire resistant materials, paper, plastic, brake linings, acoustic tiles, filters, abrasives and lubricants with inhalation causing collagenous plaques and thickening and adhesions of the pleura. Exposure to vinyl chloride results primarily from the release of gaseous vinyl chloride during its polymer 1zaTion to polyvinyl chloride and causes angiosarcoma of the liven.- (76 Refs) c c c c c c L L (_ *l ; .. 4. * \ .'c!?** ^*4*'//V-A*'* y.r". 00005668 VINYL CHLORIDE PAGE 90 180 AU - Suzuki Y AD - Environmental Sciences Lab.i Dept. Community Hedieine, Mount Sinai Sen, Medicine City Univ, New York> One Gustave Levy Place> New York, NY, 10029 TI - NONNEOPLASTIC EFFECTS OF VINYL CHLORIDE IN MOUSE LUNG. SI - ICDB/60/52336 SO - Environ Res! 21(1):235-253 1980 LA - ENG AB - In a previous study, a high incidence of pulmonary tumors (alveologenic neoplasia in mouse lung exposed to vinyl chloride at heavy dose (2,500 and 6,000 ppm) for long durations (5 and 6 mo)) was reported. In the present study, nonneoplastic effects in mouse lung were investigated by light and electron microscopy. As major light microscopic alterations, proliferation and hypartrophv of the 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, mobilization of alveolar macrophages, and occasional presence of peribronchial of bronchiolar chronic inflammation, were observed. Electron microscopically, Clara ceils 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 endothelium. (Author abstract) (32 Refs) 181 AU AD TI SI SO LA AB - Pater S ", Ungvary G Lab. Human Genetics, State Inst. Hyqiens, Budapest, Hunqary - LACK OF MUTAGENIC EFFECT OF VINYL CHLORIDE MONOMER IN THE MAMMALIAN SPOT TEST. - ICOB/CO/52312 - Mutat Res) 77(2)1193-196 I960 ENG A mammalian spot Test was used to determine whether vinyl chloride monomer (VCM) is able to induce somatic gene mutations. C57BL/6J Han f emale mice (a/a) wild-type) were mated to The Han rotated-bred males of The T-sTock strain (a/a, non-agouti', b/b, brown; cchp/ccho, chinchilla, and pinked eye dilution; dse/dse, dilute and short ear; s/s, piebald spotting). Ten days later, the females ware exposed to VCM (12,000 mq/metorj; 6,600 ppm) for 5 hr. FI offspring were examined at 3-5 wk postOartum for the aopearance of mosaic coat colors. As a positive control, the ability of cyclophosphamide (CP; 10 mg/kg) to induce colored spots In FI hybrids was examined. There was no difference in av 00005669 VINYL CHLORIDE PAGE 91 litter slge at birth or at 3-5 wk after birth for the VCfli CP> or control groups. No offspring of the VCM-treatad group had abnormal morphology; mid-ventral unite spots appeared at a frequency of 2.8'/., not significantly di fferent from controls. In the CP group, there were significant differences in the number of white and colored spots. The colored spots were brownish and distributed randomly among litters. Toxicity studies showed that the dose of VCM was just tolerablei but not yet toxic for the mice. These results provide no evidence that VCM induces somatic gene mutations. (33 Refs) 132 AU - Bingham E AD - Occupational Safety and Health Admin.i Dept. Labor> 200 Constitution Ave.t Room N3713i Washington, DC, 20201 TI - OCCUPATIONAL EXPOSURE TO VINYL CHLORIDE AND POLYVINYL CHLORIDE. SI - ICD3/00/69699 SO - Fed Regist; 65(20 ) :6668-6669 1930 LA - ENG AD - The time period for submission of written comments in resoonse to a request for information on vinyl chloride and polyvinyi cnlortde is extended until Nay 9, 1930. (no Refs) 183 AU - Laib RJ ; Bolt HM AD - InstituT fur Toxikologie, Universitat Tubingen, Uilhelmstrasse 56, D-7600 Tubingen 1, U. German'.' TI - TRANS-NENBRANE ALKYLATION: A NEW METHOD FOR STUDYING IRREVERSIBLE BINDING OF REACTIVE METABOLITES TO NUCLEIC ACI05. SI - ICDB/S0/69072 SO - Biochern Pharmacol; 29(31:669-652 1930 LA - ENG AD - A new method for alkylation of nucleic acids in rat liver microsomal systems bv metabolites of xcnobiotics is described and con.pared to a conventional method. Mi crosomes for both methods Were prepared from livers of male Wlstar rats! microsomal preparations were incubated with an NAOPH-regeneratinq system Under' an atmosphere containing vinyl chloride (VC). In the conventional method (A), polyadenylic acid (poly A; 2 mg/ml) was added directly to microsomal preparations; incubation preceded at 37 C for 65 min. In the trans-membrane method (B), microsomal biotransformation and the binding reaction were separated into two compartments by polyamide molecular sieves. The nucleic acid soln, containing Z mg poly A/ml, was placed in capillary membrane fascicles. The membrane's skeleton was 200 microns thick and the active separation membrane was 0.5 microns thick. The fascicles were bent around a perforated plastic rtnq and placed in an Erlenmeyer flask; the microsomal incubation mixture surrounded the fascicles. The system was Incubated at 37 C for 65 min under an atmosphere containing VC. In both methods, the remaining poly A mixture was dialyoed, iyepht1iced> and hydro lyced", the resultant nucleosides were separated by chromatography. Both methods led to the formation of 1,N(6 )-athenoadenoslne (EA) moieties in poly A", EA was the major product. Method B produced 10/ less EA than method A. The advantage of method B was that it 00005670 VINYL CHLORIDE PAGE 92 c eliminated problems of recovery of The alkylated nucleic acid after incubation. With method Ai only AS.6 +-5.7X poly A was c recovered; with method Bi 06.0 +-1.72 poly A was recovered. (10 Refs J 189 AU - 2ajdela F ; Croisy A ; Barb in A I Malaveille C ; Tomatis L AU - Bartsch H AD - Unit Chemical Carcinogenesis, Internalional Agency Re3. Cancer, 150 cours Albert-Thomasi 69372 Lvon Cadex 2, France TI - CARCINOGENICITY OF CHLOROETHYLENE OXIDE, AN ULTIMATE REACTIVE METABOLITE OF VINYL CHLORIDE, AND BISl CHL0R0METHYL JETIIER AFTER SUBCUTANEOUS ADMINISTRATION AND IN INITIATION-PROMOTION EXPERIMENTS IN NICE. SI - ICD3/0O/A5621 SO - Cancer Res; 90(2):352-356 1930 LA - ENG AB - Repeated sc administration of chloroethylene oxide, a reactive metabolite of the carcinogen vinyl chloride, induced local tumors in mice, with an incidence comparable to that of bis(chloromethyl lather, a structurally related human and animal carcinogen, when both compounds were applied at max tolerated chronically toxic doses; no tumors distant from the injection site ware produced. Qis(chloromethy1 )ether, chloroethylene oxide, and its rearrangement product chloroacetaldehvde. a highly toxic compound, were further tested in an initiation-promotion experiment. Application to The skin of a single dose of either bis(chloromethyl )ether cr chloroethylene oxide, followed by 3 x ukly applications of 12-0-n-tetradacanoylphorbol-13-acetate for 92 wk, produced skin tumors in mice; chloroacetaldehyde under comparable conditions produced no increase in benign or malignant tumors. A good correlation between The chemical reactivity, on the basis of hydrolysis constants in aqueous media, and the Careinoqonlcify of the three compounds was noted. Our results support the hypothesis That epoxidation of the ethylenic double bond in vinyl chloride yields an ultimate carcinogenic metabolite, chloroethylene oxide, a hiqhly reactive compound which appears also to be largely responsible for the known genetic changes caused by the parent compound. (Author abstract) (36 Refs ) IQ5 AU AD TI SI SO LA AB Sabadie N i Malaveille C ; Camus AM ; Bartsch H Unit Chemical Carcinogenesis, International Agency for Res. cn Cancer, 69372 Lyon Cedex 2, France COMPARISON OF THE IIYDROXYLATION OF BEM20IA1PYPENE WITH THE METABOLISM OF VINYL CHLORIDE, N-NITR053M0PPH0LINE. AND N-NITEOSO-N*-METHYLPIRERAZINE TO MUTAGENS BY HUMAN AND RAT LIVER MICP05CMAL TRACTIONS. IC03/80/92202 Cancer Res', 9011 >119-126 1930 ENG Carcinogen metabolism in vitro was studied in 20 surgical liver specimens front adult male and female human subjects. A 60-fold inter1ndlvidual variation in aryi hydrocarbon hydroxylase 00005671 VINYL CHLORIDE PAGE 93 Cbenzo( a Ipyrene hydroxylase! activity uas seen; the capacity to convert vinyl chloride, N-nitroso-N'-methylpiperezine, and N-ni trosoniorpholine into electropni les mutagenic to Salmonella typhimurium varied 9-, 17-, and 35-fold, respectivaly. The mean enzymic capacity relative to that o-f liver from untreated rats uas 89/t for vinyl chloride, 92k for H-ni trosomorpholine, and 380X for N-niTroso-N'-methylpiperazine. When aryl hydrocarbon (benzol a Ipyrona) hydroxylase activity in human liver specimens uas plotted against mutagenicity in S typhimurium mediated by liver microsomes from the same specimens, a positive correlation uas obtained in the presence of vinyl chloride (r - 0.551 p less than 0.1), N-ni trosomorphol ine (r = 0.661 p less than 0.01), or N-ni troso-N1-methylpiperazine (r = 0.9'*; p less Than 0.01), The results are discussed in relation To the possible development of methods for assessing rates of metabolism of environmental carcinogens in human subjects in vivo using nontoxic drugs that are metabolized by the same enzymes That metabolize carcinogens. Hepatic aryl hydrocarbon tbenzo(aJpyrene) hydroxylase activity following treatment of rats uith phenobarbitone, pregnenolone-16alpha-carbonitrile, dibenamine, ami noacetoniTrile, or disulfiram, but not after Treatment ulth 3-methylcholanthrene, snowed a positive correlation uith the mutagenicity of the respective 9,000 x gravity liver supernatant fraction mediated in the presence of N-n1trosomorpholine, vinyl chloride, or aflatoxin Bl. These data lend further support That cytochrome P-950-1 inked monooxygenases in rat 1iver convert N-nitrosomorpholine, vinyl chloride, and aflatoxin Bl into mutagenic electrophiles. (Author abstract) (53 Refs) 186 AU - Neselson NS A0 - Harvard Univ.t Cambridge, MA TI - CHEMICALS AND CANCER. SI - ICOB/QI/10205 SO - Chemicals and Cancer. Boulder, CO, Colorado Associated University Press . 23 pp. , 1979. LA - ENG AB - Various evidences for the environmental etiology of cancer are reviewed with special attention to identification of environmental carcinogens. In addition to cigarette smoking which uas proved to be the principal cause of lung cancer, several other carcinogens were found to cause an elevated risk of cancer of the liver (vinvl chloride, aflatoxin Bl ), bladder (9-aminobiphenyl , benzidine, cn lornaphnzine , 2-napnthv1 amine ), skin (arsenic, UV light), lung (asbestos, bis(chloromathy1 )eTher, mustard qos>, waqina (diethylsTIIbesTrol ) , and corpus uteri (estrogens). High energy radiation uas found to Induce 'T.rious types of cancer, and benzene uas found to induce leukemia. For most of common types of cancer, the Incidence Increases ulth Increasing age. Depending on the tvpe of cancer, the Incidence increases as the power of age, The power generally ranging between 9 and 6. These findings are consistent uith the muliistep mechanism of carcinogenesis. Experimental studies indicate that the duration of exposure rather than Tne chronological age is the R&S 139073 00005672 (' VINYL CHLORIDE PAGE 96 c effective time factor in the carcinogenesis. Thus> even if exposure of a population To a carcinogen for one decade induces c an extremely low cancer rate. The raTes afTer several more decades can increase significanTly. Numerous chemicals induce Tumors in experimenTal animals without inTeraction with so-called promoters. Nearly all of these carcinogenic chemicals also induce c mutations in certain bacteria species. The accuracy of shorT term tests for carcinogenicity ranges from 067 to 977.. It is emphasized That shorT Term TesTs and epidemiological studies may be used to identify carcinogens responsible for some of the Common cancers. (26 Refs) 107 AU - Stern R AD - Dept. Fathology. Univ. California. San Fransisco. CA TI - EXPERIMENTAL ASPECTS OF HEPATIC FIBROSIS. SI - IC0B/81/93797 SO - Prog Liver Dis! 6:173-185 1979 LA - ENG AD - A new conceptual framework and model systems to aid in stimulating research in hepaTic fibrosis were reviewed. It was concluded That in the study of human fibrosis, the only relevant model appears to be the human. The human has a more vigorous fibrotic response to injury Than any other organism. Also. The angiosarcoma That develops in humans after vinvl chloride exposure is accompanied by vigorous fibrosis. Thus Tissue culture systems to grow human liver cells take on increased importance in attempts To recreate the fibrous response in vitro. One (. exploitable model of hepatic fibrosis is The scirrhous response To metastatic Tumor. Malignant epithelial cells in The liver induce a dense fibrous response. IT has not vet been established if collagen is elaborated by The Tumors. (76 Refs) ( 108 AU - Efthymiou ML AD Service du Pr Fournier. HopiTal Fernand-Widal. 200, rue du Faubourg Saint-Denis. 75675 Paris Cedex 10, France TI HEPATOTOXIC INDUSTRIAL SOLVENTS. SI ICD3/S1/91806 SO Med Chir Dig) 8(5):381-382 1979 LA FRE A3 Solvents and other hepatotoxic industrial substances are reviewed. The Toxic effects of These substances can be manifested in hepatitis, cirrhosis, granulomatosis, steatosis, enzyme Induction and inhibition, and hepatic Cancer. The carcinogenic hepatotoxic industrial substances include vinyl chloride, niTrcsamlnes , trInitrophenyImethyl nltrosamine, Tannins, d1 me thy1 am 1 noazobenzene, As, Se> and Th, (2 Refs) JJ Ui co to o ~n! 4* ^^':"vv c c . c OOOOS673 VINYL CHLORIDE PAGE 95 139 All - Con so F AD - Centre Anti-Poisons de Paris, Hopital Fernand-Widal> 200 Fg ST-Oenis, 75010 Paris> Franca TI - HEPATOTOXICITY OF CHLORIDE SOLVENTS DERIVED FROM ALIPHATIC HYDROCARBONS AND OF VINYL CHLORIDE. SI - ICDB/31/91802 50 - Mad Chir Dig! 8(5):931-933 1979 LA - FRE AB - The hepatotoxicity of aliphatic chloride derivatives varies. The hapatotoxicity is related to the metabolic transformation of the compounds into electrophilic intermediates capable of binding covalently to nucleophilic substances, such as glutathione, and structural and nuclear proteins. Inhalation of carbon Tetrachloride, chloroform, 1,2-dichloroethane, Tatrachloroethane, and 1,2-dichloroprcpana has been related to the development of acute hepatitis. Repeated administration of the these solvents has been related to the production of hepatomas in animals. Trichloroethylene seems to have a low level of hepatotoxicity, but has been shown to produce hepatomas in mice. Evidence of the carcinogenicity of vinyl chloride in humans was presented soon after its carcinogenicity in animals was proven. Liver fibrosis with splenomegaly and signs of hypertension, and liver angiosarcoma resulting from exposure to vinyl chloride have been reported. The careinoqenicity of vinyl chloride has been related to its epoxy derivative. Means of detecting the liver toxicity of these solvents are described. (11 Refs) 190 AU - Buffler PA AD - Univ. Texas Medical Branch, Dept. Preventive Medicine and Community Health, Galveston, TX, 77550 TI - SOME PROBLEMS INVOLVED IN RECOGNIZING TERATOGENS USED IN INDUSTRY. 51 - ICDB/80/79935 SO - Epidemiologic Methods for Detection of Teratogens. Klingsberg MA, Weatherall JA, ed. Basel, S. Karger, Contributions to Epidemiology and Biostatistics, Vol, 1, 203 pp., 1979. LA - ENG AB - Tiie possible teratogeni c i ty of vinyl chloride, controvers i es regarding evidence of vinyl chloride-induced congenital defects, methods used for surveillance of pregnancy outcomes, rationale and methods for an ongoing study of pregnancy outcomes of wives of individuals occupat i onal ly exposed To viiv'l chloride, and problems encountered in this study are each discussed. The onqoinq studv Includes 293 emplovoes exposed to vinyl chloride and 202 employees who were not exposed. Data on pregnenev outcomes were collected via a standardized telephone interview with the wives of these employees. Various difficulties were encountered in the studv. For example, emplovees we^e seldom exposed onlv to vinyl chloride and to no other chemical agent, and other Types of exposure (eq, smoking, drinking, drugs) might have an influence on pregnancy outcome. Also, the study group is relatively small, and the reliability of recall of preqnancv outcome probably varies from individual to individual. Additional c c c c c c c c L L L c c ( / t,. /' I ** _ |TM*||*| *JJ<*.I* Vfj 00005674 VINYL CHLORIDE PAGE 96 research of a methodologic nature is needed to assess the validity and reliability of responses obtained in surveys of this type. (36 Refs ) 191 All - Coulston F ; Li j insky M ", Martin JH ; Uynder EL `> Frauley JP AU - Furman RH ; Blair EH ; Harrison Y AD - Inst. Comparative and Human Toxicology. Albany Medical Coll, of Union llniv., Albany, NY TI - GENERAL DISCUSSION: THE DELANEY CLAUSE. SI - ICDB/60/75310 SO - Regulatory Aspects of Carcinogenesis and Food Additives. Coulston F, ed. London, Academic Press, Ecotoxicology and Environmental Quality Series, Vol. 2, 397 pp., 1979. LA - ENG AB - Proceedings of a discussion of chemical and environmental carcinogens, extrapolation of experimental data concerning carcinogenesis to humans, and the developement of government policies regulating carcinogen exposure are presented. Studies and epidemiologic data concerned with the careinogenicity of vinyl chloride, diethylstilbestrol, and saccharin are examined. Current methods of testing of carcinogens are critically evaluated. The percentage of cancers caused by chemicals and by environmental aqents is debated, and the applicabi1ity of the max tolerated dose bioassay is discussed. The following four steps to be taken in any regulatory policy are outlined: 1) determination of careinogeniclty , 2) determination of the potency of the carcinogen, 3) determination of the actual risk of the exoosed population, and 4) comparison of the estimated risk with the estimated benefit, (no Refs) 192 AU - Maekaua A I Ogiu T ; Odashima N AD - Div. Pathology, Natl. Inst. Hygienic Sciences, Setagaya-ku, Tokyo 153, Japan TI - CARCINOGENICITY TEST OF HIGH MOLECULAR COMPOUNDS USED IN MEDICAL PRACTICE BY IMPLANTATION INTO THE SUBCUTANEOUS TISSUE OF RATS (MEETING ABSTRACT). SI - ICD3/80/67974 SO - Proceedings of the 33th Annual Meetinq of the Japanese Cancer Association held in Tokyo, Japan, September 1979. Japanese Cancer Association, Tokyo, Japan, 321 pp., 1979. LA - JPN AB - Eloven-wk-old Wistar rats were divided into 4 groups, each consisting of 25 male and 25 female rats. High molecular compounds used in medical practice (lnvl chlorlde-A for grouo I, vinyl chloride-8 for group II, vinyl chloride-C for group III, and hydrophobic polymer, silicone, for group IV) were cut into plates 1-2 iimi thick and 1-2 cm square and implanted into the SC tissue of the backs of the rats. Fifteen male and 15 female rats served as the controls, and Their backs were Incised but nothing was implanted. Five male and five female rats from each exper1 mental group and three male and Three female rats from the Control group were killed 3 mo after the Treatment and the rest were raised for 2 yr. Sc tumors were produced in 3 male and 5 * n c 00005675 VINYL CHLORIDE 33 fh CO CO <o o <2 PAGE 97 *V^1i^S^'V'.*-,JJ'; ,,,,, c C c c female rats in group li 4 male and 6 female rats in group II. 9 male and 13 female rats in group III. and 1 male and Z female rats in group IV. Frequency of tumor production differed from group to group; it uas greatest in group III. followed by group II and group I. and was lowest in group IV. The period at which the tumor was produced was early in groups III and II and late in group IV. All the tumors were produced where the compounds were implanted. Histologically, most were fibrosarcoma or rhabdomyosarcoma in appearance, and metastasis was observed in Some of the cases. Tumors other Than sc ones spontaneously occurring in Ulster rats, eg. testicular tumor and leukemia, were observed in the groups, including the control, but there was no difference in their occurrence among the groups, (no Refs) 193 AU - Hasegawa H ; Sato M ", Okonogi K ; Shimaoka A ; Tsuruta H AO - Natl. Inst. Industrial Health, Kawasaki. Japan TI - EXAMINATION OF WORKERS IN POLYMERIZATION PROCESS OF VINYL CHLORIDE MONOMER (VCM). SI - ICD0/80/67226 50 - Ind Health; 17(31:153-185 1979 LA - ENG AB - Results from several examinations concerning the health of workers involved in VCM polymerigation (3 different plants) are presented. Blood of 82 workers and 28 controls was tested biochemically using a battery of 25 screening tests. The amount of VCM in the blood of workers was measured, and the effect of VCM on the activity of a variety of engymes was statistically analysed. The metabolic rate of VCM was also determined. (13 Refs) 194 AU - Takahama M ; Nishibe Y j Shibata T ; Inagaki T AD - Dept. Pathology, SaiTama Medical Sch., Morayama-machi, Saitama Pref 350-04, Japan TI - MORPHOLOGICAL STUDY OF EARLY LESIONS OF EXPERIMENTAL QUINOLINE-HEPATIC HEMANGIOSARCCMA. COMPARATIVE STUDY WITH VINYL CHLORIDE MONOMER (VCM)-HEPATIC HEMANGIOSARCCMA IN MAN (MEETING ABSTRACT). 51 - ICDB/80/66905 SO - Proceedings of the 38th Annual Meeting of the Japanese Cancer Association held in Tokyo, Japan, September 1979. Japanese Cancer Association, Tokyo, Japan, 321 pp., 1979. LA - JPN AB - Three groups of male SO rats that were fed an oriental powder diet containing 0.1/ quinoline for 3, 6 and 12 mo, and were killed at the end of administration, and two groups of rats that were fed the same diet for 3 and 6 mo, and killed 12 mo after the start of treatment, were examined by light and electron microscopy. Multiple atypical growth foci of littoral cells were observed only in the group of rats administered quinoline for 12 mo. These atypical cells had carbon inclus1ve phacocytot 1c and iron pnagocytotic appearance, and many villous cell protrusions were observed in the electron micrographs, which are all characterist1c of Kuoffer cells. The cases studied in man were liver tissues around the vinyl chloride monomer (VCM )-hepa11C c c c c t ( e c c c L 00005676 VINYL CHLORIDE PAGE 98 hemangioma and nontumon coses with abnormality in liver tissues and in sinusoid wall cells. There were findings that differed from the victims of VCM poisoning such as the lack of an increase in collagen fibrils around the sinusoidal line, (no Refs) 195 AU - Infante PF AD - Industry-wida Studies Branchi Natl. Inst. Occupational Safety and Health Center Disease Control. Div. Surveillance. Hazard Evaluation and Field Studies. Cincinnati. OH TI - EPIDEMIOLOGIC APPROACHES FOR SURVEILLANCE OF GENETIC HAZARDS WITH PARTICULAR REFERENCE TO ANESTHETIC GASES. SI - IC0B/80/66263 SO - Genetic Damage In Man Caused by Environmental Agents. Proceedings of a Conference held in Oslo, Norway, May 11-13. 1977. Berg K, ed. New York, Academic Press. 551 pp.> 1979. LA - ENG AB - Genetic hazards due to anesthetic gases are discussed on the basis of epidemiological studies. Studies on spontaneous abortion, birth defects, still births, and birth wt among female anesthetists are reviewed. Studies on spontaneous abortion, birth defects, and decrease in motility of sperm and shape of sperm after male exposure to chioroprene (CP), vinyl chloride (VC), and anesthetic gases are reviewed. Evidence for cytogenetic, mutagenic and reproductive effects of CP and VC is reviewed. (19 Refs ) 196 AU - Hans Teen IL AD - Lab. Genetics, Telemark Central Hosp., Porsgrunn, Norway TI - A FOLLOW-UP STUDY OF PVC WORKERS TWO YEARS AFTER EXFOSURE. PRELIMINARY RESULTS USING SISTER CHROMATIC EXCHANGE FREQUENCY AS AN ASSAY OF GENETIC DAMAGE. SI - ICDB/80/66262 SO - Genetic Damage in Man Caused by Environmental Aqents, Proceedings of a Conference held in Oslo, Norway, May 11-13, 1977. Berg K, ed. New York. Academic Press, 551 pp., 1979, LA - ENG AB - Si star-chromatid exchange (SCE) was studied in 16 workers from a polyvinyl chloride (PVC) factory 2 yr after exposure to vinyl chloride monomer (VCM). The study included matched controls from the office employees at the factory. The results showed that the mean number of 5CEs per cell was 7,6 for the workers , and 7.5 for the matched controls, indicating that there is probably no difference in the freauency of SCEs between PVC workers and their matched controls. (11 Refs) 197 AU - Donigar 00 AD - Natural Resources Defense Council, Washington, DC TI - THE LAW AND POLICY OF TOXIC SUBSTANCES CONTROL. A CASE STUDY OF VINYL CHLORIDE. SI - ICDB/80/62520 SO - The Law and Policy of Toxic Substances Control. A Case Study of Vinyl Chloride. Baltimore, Resources for the Future, 179 po, , 1979. c c c c c L C C t 4'Zi/.--* '3 < 00005677 VINYL CHLORIDE PAGE 99 c LA - ENG AB - The federal regulation of vinyl chloride (VC) is examined to c illustrate the complexity of laws and policv relating to toxic substance control in the United States. The still incomplete regulation of VC has involved five major federal agencies operating under 15 separate health and environmenTal statutes. In 1979, the Occupational Safety and Health Administration (OSHA) c and the National Institute for Occupational Safety and Health (NIOSH) learned of the association between VC and angiosarcoma of The liver, and Thes< began preparing a workplace standard for The chemical. The regulation of any toxic substance involves complex decision making under uncertainty, and judgements about the importance of health and environmental values as Opposed economic interests. The limits of cancer risk assessment are discussed to explore the nature of scientific uncertainty in the management of hazardous substances. Experimental analysis does not give the regulatory agency a a precise estimate of the risks associated with low doses of substances that are known to cause cancer in c humans or in animals at high doses. The limits of economic and technological assessment in determining the costs of controlling exposure to a toxic substance also are reviewed. (65 Refs) c 193 AU - Kello D ; Stara JF AD - Institut za medicinska istrazivanja i medicinu rada, Zagreb, Yugoslavia TI - HEALTH EFFECT ASSESSMENT OF VINYL CHLORIDE IN THE ENVIRONMENT. SI - ICDB/00/61795 SO - Arh Hig Rada Tokslkol; 30(9)1363-397 1979 LA - SCR AB - Toxicological and hygienic studies of exposure to vinyl chloride (VC) are reviewed. Angiosarcoma of the liver was observed in workers having Inhaled VC. Similar and other tumors were found in experimental animals having inhaled or ingested VC. (179 Refs) 199 AU - Ciugudeanu M ! Metes L ; Zugravu E ; Colosi D ; Anca Z i Gabor S AU - Preda N I Suciu L AO - InstituTul de igiena si sanatate publica, Cluj-Napoca, Romania TI - STUDY OF THE BEHAVIOR OF 50ME SERUM ENZYMES IN WORKERS EXPOSED OCCUPATIONALLY TO VINYL CHLORIDE. SI - ICDB/80/60020 SO - Rev Ig CIg); 23(8)1237-291 1979 LA - RUM A3 - Changes in serum enzyme activities were studied in 89 workers exposed occupationally to vinyl chloride during synthesisAlkalme phosphatase (AP) was studied in 82 cases, gamma-glutamyl Transferase (GOT) in 82, glutamate dehydrogenase (CDH) in 73, SOOT in 89, SOFT in 89, lactate dahydroqenase (LDH1 in 76, and cholinesterase (ChE) in 89. Abnormal enzyme activities were found in 6.C9X of all patients for AP, in 20.77. for SCOT, in 92.9X for GDH, in 19,2X for SGOT, in 39. ZV. for GPT, in 5.26X for LDH, and m 3.57X for ChE. In the workers exposed to vinyl chloride less than 10 yr, increased SGPT activity was found, which is indicative of a lesion of The cytoplasm of the nepatocytes. In R&S 139078 00005678 VINYL CHLORIDE PAGE 100 workers exposed greater Than 10 yr, increased GDH and GGT activities, indicative of more severe lesions of the mitochondrial membranes, were found. The ChE activity was the only parameter to show a slight decrease, whose extent increased with increasing length of exposure. The increase was most pronounced in the SGPT activity for exposures less than 10 yr and in the GDH acTivity of exposures exceeding 10 yr. (25 Refs) 200 AU - Pialat J ; Pasquier 0 I Pahn H i Kopp N AD - Laboratoire d'Anatomie Patholoqique> CMU de Lyon, Faculte Alexis Carrel , rue Gui1laume-Paradin, 69372 Lyon Cedex 2, France TI - HEPATIC LESIONS CAUSED BY VINYL CHLORIDE MONOMER IN HUMANS. STUDY OF EIGHT CLINICOPATHOLOGICAL CASES. SI ICD3/S0/59S93 SO - Arch Anal Cytol Pathol; 27(61:361-375 1979 LA - FRE AS - The history of the industrial use of vinyl chloride monomer and the carcinogenic effects in exposed workers is reviewed: eight new cases are reported. The eiqht patients were all men rar.qing in age from 33-63 yr. They had been exposed To vinyl chloride fumes in the course of their work for periods of 10-30 yr. Six patients had angiosarcomas of the liver, one had a hepatoma, and one had hepatic fibrosis with portal hypertension. Of the seven patients with neoplasms, five underwent hepatectomy of the involved hepatic lobe', one was alive 13 mo after surgery', but the others died 1 day to 2.5 mo after the surgery. Two patients did not undergo surgery for their liver tumors and lived 2.5 and 0 mo, respectively', after diagnosis. The patient with fibrosis was treated medicallv and is in good health 2 yr after diagnosis. Histogenic and pathogenic theories of vinyl chloride toxicity' are discussed. (Ill Refs) 201 AU - Pollice L AD - 3ari, Italy TI - PRIMARY VASCULAR TUMORS OF THE LIVER (MEETING ABSTRACT). SI - ICDB/60/S97S3 SO Pathology; 165(1/2):165 1979 LA ENG AB The main primary vascular tumors of the liver include cavernous and sclerosing hemangiomas, infantile hemanqioendotheliomn and angiosarcoma, (so called Kupffer cells sarcoma). Os the basis of personal observations and of the data of The literature, n unlfvinq pathoqene11 c concent of these tumors Is proposed. In particular the two different histoloaical patterns of hepatic infantile hemangioendotheliomas Are illustrated and their position within an oriqinal classification of primary' hepatic Tumors Its Infancy' and childhood is proposed. Furthermore the oncogenic role plaved by env1ronwenTal and occupational acents (namely polyvinyl chloride, thorotrast, arsenical intoxication) on the origin of hepatic angiosarcomas as already reported by several authors, is discussed. Finally, a case of hepatic atsgl osarcoma, observed in a 26-yr-old men, after a 7 yr period of e.-.posure to aery ion i Tr i le, a vinyl cyanide widely used in the 00005679 VINYL CHLORIDE PAGE 101 manufacture of synthetic rubber, is described) and the possible correlations with vinyl chloride induced tuitions are proposed, (no Refs ) 202 AU - de Laguna JC AD - No affiliation given TI - POSSIBLES FACT0RE5 AN3IENTALES EN LA ETIOLOGIA DEL CANCER. CP0SSI3LE ENVIRONNENTAL FACTCRS IN THE ETIOLOGY OF CANCER]. SI - ICDB/80/56723 SO - Gac Ned Hex! 115(61:253-263 1979 LA - SPA AB - The problem of determining causality in the study of cancer was considered. It has been shown that risk of developing lung cancer increases inversely with age at which smoking is begun, directly with the number of cigarettes smoked, and directly with the degree of inhalation. Risk of developing cancer of the mouth increases not only with number of cigarettes smoked per day, but also with quantity of alcohol consumed, and is greatest for those who smoke over A0 cigarettes/dav and drink over 1.5 ounces of alcohol/day. Other agents associated with lung cancer include arsenic, asbestos, chrome, carbon, iron oxide, mustard gas, nickel, petroleum, ionizing radiation, and bIs-(cnloromethy1 1 ether. Exposure to ionizing radiation and to benzene has been found to Increase the incidence of leukemia. Carbon products and aromatic amines have been associated with bladder cancer, arsenic and vinyl chloride with 1i,,er cancer, and chrome, isopropyl alcohol, nickel, and the dust of wood and hides with cancer of the buccal cavity and nasal sinuses. Dietary factors including bervlliu.ii, lead, arsenic, and iodine are carcinogenic. Deficiencies of iron, molybdenum, magnesium, and zinc are associated with certain cancers. Other carcinogenic substances include fertilizers, pesticides, antibiotics, food additives, aflatoxins, ni trosoamines , and mans' forms of hormones and pharmaceuTicals . Dietary an11-carc 1 nogens include selenium, s' 1 t am 1 ms C and E, h'/droxs'toluene , and hydroxyani sole. It was estimated that 99,500/193,600 expected deaths due to cancer could be prevented. (23 Refs) 203 AU AD TI SI SO LA AB - Palmqvist U - Uislfos kemi AB, Stenunqsund, Sweden THE LC.JEST HARMLESS DOSE IN PRACTICE IS ZERO. ICDB/30/51CCA Kem Tidskr; 91(1A):36-A0 1979 SUE ExperI mental and eoldemiologicai studies on the carcinogenic effects of nitroso compounds and other substances are reviewed. Certain carcinogenic substances, especially nitroso compounds, show a surprising orqano tr op I s.n . Me Thvlalk"l-N-n I t r os am i ne induces tumors of the esophagus, M-methy1-N-nlirosoacetylurea qiven po causes tumors of the glandular stomach, N-propy1-N-nItrosourea given po induces tumors of the large intestine, N-methy1-N-nItrosourea given iv causes brain Tumors, and N-butyl-N-ni trosourea given po causes leukemia. The A..;es test 00005660 VINYL CHLORIDE PAGE 102 indicates that the active mutagenic substance in a test of vinyl chloride is alpha-chloroacetaldehyde. Trist2>3-dibromopropy1 Iphosphatej which contains the carcinogenic impurities 1.2-dlbromo-3-chloropropane and 1i2>3-Tribromopropane, is also highly mutagenic. (5 Refs) 204 AU - Krahn DF AD - Haskell Lab. Toxicology and Industrial Medicine. E.I. du Pont de Nemours A Co. . Wilmington. DE. 19893 TI - UTILIZATION OF THE CHO/HGPRT STSTEM: METABOLIC ACTIVATION AND METHOD FOR TESTING GASES. SI - ICDB/60/51114 SO - Mammalian Cell Mutagenesis'- The Maturation of Test Systems. Hsie AW, O'Neill JP. McEiheny UR. ed. Cold Spring Harbor, Cold Spring Harbor Laboratory. Banbury Report , tip. 2, 504 pp. , 1979. LA - ENG AB - The use of the CHO/HGPRT (hypoxanthine guanine-phosphoribosyltransferase ) assay to study the mutagenic activities of gases, volatile liquids, and chemicals requiring metabolic activation is discussed. The assay yielded reproducible results with structurally diverse chemicals and chemicals requiring activation. The storage of S-9 did not diminish its ability to activate dimethvlni trosamine (Dtlii), 2-acetylam 1nofluorene . or 7,12-dimethylbengta lanthracene. The mutagenic activity of DMN increased as the concentration of S-9 increased. The proposed procedure for testing gases and volatile liquids proved workable and responded to various compounds as expected on The basis of results from other toxicology tests. However, in contrast to results obtained in microsomal assays with Salmonella typhimurium, vinyl chloride was mutagenic in The CHO/HGPRT system only with a complete activation system. IT was concluded that the CHO/HGTRT system in its present form appears to be an appropriate tool for identifying potential mutagens and carcinogens, (8 Refs) 205 AU - Kroes R AD - No affiliation given TI - RISKS OF NON-INDUSTRIAL CHEMICAL SUBSTANCES. SI - ICDB/00/51002 SO - Chemisch Ueekblad; 70(51/521:43-50 1979 LA - DUT AB - The ecological and hygienic problems of toxic and carcinogenic substances in air, water, drinking water, food, and soil are discussed. Acceptable daily intake and relative risk values are given for carcinogenic substances (aflatoxln Bl, vinyl chloride, saccharin, eyclamate. and nltrosamlnes ). (12 Refs) 00005681 VINYL CHLORIDE PAGE 103 206 AU - Althouse R t Tomatis L I Huff J ; Uilbourn J AO - Internat i onal Agency Tor Res. on Cfln:jr. > Lyon, France TI - CHEMICALS AND INDUSTRIAL FR0CE5SES ASSOCIATED WITH CANCER IN HUMANS. IARC MONOGRAPHS, VOLUMES 1 TO 20. SI - ICDB/80/99695 SO - IARC Monogr Eval Carcinog Risk Chem (Suppl 1): 71 pp., 1979. LA - ENG AB - The program and findings of the International Agency for Research on Cancer (IARC), established in 1917, are summarized. The objective of this program has been to publish monographs on the careinogenic1ty of chemicals to union humans are exposed. Data on human and experimental animal careinogonic1ty for more Than 350 chemicals and industrial processes are evaluated. Human daTa were available for only 98 chemicals. In 1977, a recommendation was made to regard chemicals known to be carcinogenic in animals as potential human carcinogens, and was adopted beginning with volume 17. Data from the earlier volumes were reewaluated in light of This decision. By The end of 1973, 192 of 992 chemicals and processes evaluated showed carcinogenicity in animals; data on 59 of these chemicals or processes were derived from both human and animal studies. Evidence of careinogeniclty was classified as sufficient, limited, inadequate, negative, or nonexistent. Human data were derived from case reports, epidemiological studies, and case-control and cohort programs. Cause-and-effeet was inferred from dose-response relationships. Eighteen chemicals or chemical processes are shown to pose a carcinogenic risk to humans. These include 9-aminobiphenyl, arsenic and certain arsenic compounds, asbestos, manufacture of auramine, benzene, benzidine, N,N-b i s ( 2-c'nloroe thy 1 ) - 2-naphthylami no ( chlorna.phaz i ne ), bi s (chloromethyl lether and Technical grade chlcromethyl methyl ether, chromium and certain of Its compounds, d1 ethylstilbestro1, underground hematite mining, manufacture of isopropyl alcohol by the strong acid process, melphalan, mustard gas, 2-naphthvlamine, nickel refining, soots, tars, and mineral oils, and vinyl chloride* Eighteen other compounds were Judged probably care 1 nogenic to humans, and eighteen could not be classified. Evidence supporting the evaluations appears in a detailed index. (29 Refs ) 207 AU AD TI SI SO LA AB Resnick MA Dept. Biochem1stry, Coll. Medicine, East Tennessee State Univ., Johnson City, TN THE INDUCTION OF MOLECULAR AND GENETIC RECOMBINATION IN EUKAPYOTIC CELLO. ICOD/CO/99533 Ad,, Radi at Biol; 8:175-217 1979 ENG Mechanisms of recomb i na t i on induction in euk.aryotic cells are re*,levied. Improved methods for detecting sister chromatid exchanges (SCE ) har'e led to increased interest in the induction of recombinatlon by mutagenic agents. Classically, recombination *-vL'-'V^vr- :>. - v- c 00005682 VINYL CHLORIDE PAGE 104 cc has been identified with meiosis, and expression of it manifested in cross i ng-over during synapsis. Many of the DHA engymes c involved have been found to be common to processes of DNA repair in mitotic cells. Swapping of DNA strand segments leads to formation of hybrid regions. If a mismatched base pair occurs in JO fio C/) the hybrid regioni it is termed a heteroduplex. Correction leads to gene conversion! or nonrec1procal recombination. Both --L ( reciprocal recombination between genes and gene conversion may occur spontaneously in mitotic calls, or may be induced by UV, co co o x-rays> hyperthermia and various mutagens (recombinogens ). All 00 chemicals Known to be mutagenic in yeast have been found to be CO recombinoqanic as well. Chemicals with both properties include vinyl chloride* mitomycin C. naphthylaminesi bleomycin, and formaldehyde . Since most UV-induced recombination can be rewersec by photcreactivation, the induced lesions have been presumed to c( be pyrimidine dimers. Semiconservative replication seems not to be involved in recombination; most evidence indicates a repair function. The spontaneous frequency of recombination is very high c cin humans with disorders (Blooms syndrome, xeroderma pigmentosum, Fanconi's disease, and ataxia telangiectasia) in which there is also a high incidence of cancer. Studies of recombination may be important for understanding mutagen-induced changes such as Tumor induction. (180 Refs) 203 AU - Retv J AO - Rhone-Poulene Polwmeres, 69190 Saint-Fons, France TI - THE NINTH CASE OF ANGIOSARCOMA OF THE LIVER IN A WORKER IN THE FIELD OF VINYL CHLORIDE POLYMERISATION. SI - ICDB/80/49516 c. SO - Arch Mai Prof; 40( 6/7)-'711-743 1979 LA - FRE ct AB - A case of liver angiosarcoma in a 63-yr-old man exposed To vinyl chloride for the previous 28 yr is reported. The patient presented with a 18-yr history of intermittent hypochondrium pain, wt loss, and hepatomegaly; 4 yr previously the patient had been treated for jaundice with increased alkaline phosphatase activity. Angioqraphv and aortography showed a well delimited c mass in the postero-inferior region of the right lobe of the liver. The patient underwent surgery and three tumoral masses were excised; the left lobe and segment IV were normal. The histological diagnosis of hemangio-endothellosarcoma was made. c The postoperative course was complicated by a biliary fistula and The patient was discharged 4 mo after surgery. Seventeen mo after surgerv, the findings of splenic and hepatic scintigraphv were normal. Three mo later, the patient had a recurrence of the L fistula, which required surgerv, and he died pos t opera t i'-e 1 y . Autopsy showed extensive alterations of li^er tissue and the presence of several tumoral nodules (massive angiosarcoma), (no Refs) c 00005683 VINYL CHLORIDE PAGE 105 209 AU - Popper H \ Thornes LB AO - StreTTon Lab. for Study of Liver Oisease, Mount Sinai Sch. Medicine. New York, NY TI - ENVIRONMENTAL LIVER TUMORS. SI - ICDB/SO/49233 SO - Kurume Med Jt 26(31:189-204 1979 LA - ENG AD - The induction of liver tumors by environmental factors is reviewed, and the significance and incidence of environmental hepatic tumors are presented. Possible factors in the careinoembryonic chain which determine the development of carcinoma development may be the amount and lifespan of the bioactive agent, the removal or alteration of portions of DMA by endonuclease repair enzymes, and the fixation of DMA alterations Environmental agents mav increase the availability of bioactive metabolites, stimulate hepatocellular prol1feration . or serve as the carcinogen. It is noted that there is little evidence of careinogenicity of polycyclic hydrocarbons and N-nitroso-ccmpounds in humans. The incidence of steroid-induced hepatic tumors that may be due to contraceptive druqs is very low. The characteristic morphologic and clinical sequence associated uith vinyl chloride and other agents was presented, and the evolution of human lesions towards anqiosarcoma bv two different pathways was discussed. Several agents in man elicit sequences of hepatic change which start with mixed nodular hyperplasia and progress to anqiosarcoma or hepatocellular carcinoma. (44 Refs I c c c c 3J w 00 (O O 00 -pk 210 AU - Matos EL AD - Institute de Oncolcgia Anqel H. Rofto, Avenida San Martin 5431, 1417 Buenos Aires, Argentina TI - OCCUPATIONAL CANCER. SI - ICDB/30/47234 SO - Medicina (B Aires); 39(4):536-539 1979 LA - SPA AB - Discoveries of carcinogenic substances in occupational environments are reviewed. Since the discovery in 1775 that scrotal cancer occurred with high frequency among chimne" sweeps, and the observation in 1895 that workers in the dye industry showed high incidence of bladder cancer, many similar correlations have been made. Recently, the Internationa 1 Agency for the Investigation of Cancer analyzed 330 chemicals or industrial processes and found that 26 were associated with human cancer, 10 of which were involved with occupational hazards. Previous studies have shown that 230 of these chemicals or processes had carcinogenic potential, and 111 were capable of productnq malignant tumors in many species and strains. Substances or processes known to cause occupational cancer in man Include isopropyl oil and nickel (cancer of the nasal cavity); asbestos, bl s-chloromethy 1 ether, c'nlor omet hy 1-me thy 1 ether, chromiun, mustard cas , hematite, and aromatic polycyclic hydrocarbons in carbon tars (lung cancer); aromatic polycyclic C c. c L e c 00005684 i. VINYL CHLORIDE PAGE 106 cc hydrocarsons in soot and mineral oil* and arsenic (skin cancer)! 4-ami nobiphenyl, auraminei benpidine. and 2-naphthylamine c c(bladder cancer); aflatoxin, and vinyl chloride (liver cancer)! cadmium (cancer of the prostate); and benpene (cancer of the hematopoietic system). Not all persons exposed to these substances develop cancer. It was suggested that other factors c (like the inducible hydroxylase of aromatic polycyclic hydrocarbons act upon substances (In this casei particularly bengpyrene ) so as to unleash their carcinogenic potential. It is wall established that certain diets and smoking con create a micrcenvironment favorable for tumor development. (19 Refs) 211 AU - Rety J ; Bory RM ; Spay G ; Beurlet J ; Pialat J c AD - Rhone-Poulcnc Polymeres, 69190 Saint-Fons, France TI - THE TENTH FRENCH CASE OF ANGIOSARCOMA OF THE LIVER IN A WORKER EXPOSED TO VINYL CHLORIDE. SI - IC08/80/46467 c SO - Arch Mai Prof; 40(6/7)1743-744 1979 LA - FRE AB - A 58-yr-old man* who had been exposed to vinyl chloride for the previous 21 yr> was admitted with asthenia, wt loss (3 kg in 3 wk), anorexia, epigastric discomfort, constipation, and increased alkaline phosphatase activity. Laparoscopy showed a hypervascula- tumor (8-10 cm) of the right lobe of the liver. The patient underwent right paramedian thoracic laparotomy and hcpatectomy, histological diagnosis of angiosarcoma was made, and the patient died of pulmonary embolism 10 days later, (no Refs) 33 ft0 <*> \ 212 AU - Miguet JP ", Allemand H I Bernard F ; Greff M J Vuitton D AU - Glilet M ; Caravon P AD - Service d'hepato-gastroenterologi e, CHU de Besancon, 2, pi. Saint-Jacques , F 5030 Besancon, France 00 <o o oo TI - A CASE OF PORTAL HYPERTENSION AND LIVER FIBROSIS FOLLOWING O) CHROMIC EXPOSURE TO VINYL CHLORIDE. SI - ICO3/80/46428 SO - Nouv Presse Med; 8(1):3364 1979 LA - FRE AB - A 46-yr-old man, having 15 vr contact with vinyl chloride, was admitted with ruptured esophageal varicosities, hepatomegaly, Cl. splenomegaly , and portal hyper tension. The patient underwent surgery and an end-to-end spleno-renal anastomosis was performed. M1croscop1c examination of the 1iwer showed moderate fibrosis. (5 Refs ) 213 AU - Du JT ; Sandoc JP ! Tseng MT ; Tamburrg CH AD - Div. Digestive Diseases, Nutrition, Uni'/. Louisville Sch. Medicine, Louisville, KY, 40232 TI - BIOCHEMICAL ALTERATIONS IN LIVERS OF PATS EXF05ED TO VINYL CHLCRIDE. c. SI - IC03/80/45375 SO - J Toxicol Environ Health; 5(61:1119-1132 1979 LA - ENG :*v A3 - Male Sprague-Dawley rats were exposed to vinvl chloride (VC) gas 1 . a, . \ - " r . . r. "fr'vii c c 00Q056S5 VINYL CHLORIDE PAGE 107 in four experiments (15,000 ppm, 2-8 hr/day> 1-4 uk, total 14-137 hr) to study liver responses in early enzyme changes, The role of the hepatccyte in VC-induced injury and the development of angiosarcoma. Increases ;n glutathione reductase and giucose-6-phosphate dshydrogena.se, and reduction in glucose-6-phosphatnse occurred. Light microscopy showed no hepatocellular changes, but electron microscopy revealed dilation of The rough endoplasmic reticulum in some hepatocytes after exposure to VC for 137 hr. There uas also an increase in the cytoplasmic density of the affected cells, and other hepatocytes shewed small clear patches which tended to aggregate near the cell periphery. The enzymatic changes observed were considered to reflect early hepatocellular adaptations to VC. (41 Refs) c ( ( c 214 AU - da Meester C t Poncelet F ', Roberfroid M ", Hercier M AD - Lab. 8i otoxicologie, Ecole Pharmacia Univ. Catholique Louvain, 73, A", E. Mounter, B-1200 Bruxelles, Belgium TI - VIHYL CHLORIDE: DIRECT OR INDIRECT MUTAGEN, SI - ICDB/80/45234 50 - Arch Int Physiol Biocnim; 37(31:620-621 1979 LA - ENG AB - The substance vinyl chloride (VC) is a reactant in the manufacture of polyvinyl chloride (PVC) used in food packaging. VC increases chromosome aberration rates, and is associated with liver angiosarcoma in those workers exposed to air containing VC. The dependence of VC mutagenicity (M) on metabolic activation uas studied using the Ames test, exposing the plates to a 2X VC atmosphere. This mutagenesis appeared to require post-mitochondrial (59) fractions from mouse liver added to the cultures; these fractions converted VC into an unidentified volatile mutagen. (3 Refs) c c 33 CD 215 AU - Asplund I AD - Ho affiliation given TI - LIST OF MAXIMUM ALLOWABLE CONCENTRATIONS FOR AIR POLLUTANTS. 51 - ICDB/60/44290 SO - Kernisk Tldskrift; 91(111:24-27 1979 LA - SHE A3 - The new list of air pollutants which became effective in Sweden on January 1, 1979 is presented. The list includes carcinogenic compounds, such as aery 1 onitrl1e, asbestos, banco(a Ipyrene> benzyl chloride, beryllium, dimethyihvdrazina , dioxane, hydrazine, chloroform, carbon Tetracn lorida , 2-nltroprepane, poiycnlorInated biphenyls, trinickel disulfide, and vinvl chlorid:. Max allowable atmospheric concentrations of these and other compounds are listed, (no Refs) W CD O 03 O) L L ...- ' -yy itd.-.- -ns c 00005666 VINYL CHLORIDE c PAGE 108 c 216 AU - Suskind RR c AD - Inst. Environmental Health Kettering Lab., Coll. Medicine. Univ, c Cincinnati, Cincinnati, OH TI - CUTANEOUS REACTIONS TO COSMETICS. SI - ICD3/80/93750 c SO - J Dermatol (Tokyo); 6<9):203-209 1979 ( cLA - ENG AB - In general discussion of problems associated with cutaneous reactions to cosmetic preparations and ingredients, it is mentioned that some local skin reactions may be of a photosensitizing nature. Animal and in vitro studies shou that certain ingredients of cosmetics may be mutagenic (some permanent hair dyes) or carcinogenic (2,9-tolunediamine and c 2,9-diam 1noanisole; aioxane and dimethoxane! eaptan; safrole, isosafrole, and dihydrosafrole; oil of calamus; vinyl chloride; tr i chlorae thylene ", and chloroform). (8 Ref3 ) c 217 AU - Davis DL ", Magee BH AD - Toxic Substances Program, Environmental Law Inst., Washington, c(, DC, 20136 TI - CANCER AND INDUSTRIAL CHEMICAL PRODUCTION (LETTER TO EDITOR). SI ICD3/G0/92919 SO - Science; 206(99251:1356-1357 1979 <; LA - ENG AB - Cancer risks associated with industrial chemical production and use were studied to determine regulatory priorities and cancer rates were examined in light of the production histories of industrial carcinogens. It is too soon to reach any conclusions about the magnitude of the cancer risk to the general population posed by industrial chemicals. The annual production of boncene, perch1oroe thy lene , vinyl chloride, acrylonitrile , plastics and resin materials, plasticizers, flavors and perfumes (benzenold J3 and naphthalanoid), and food, drug, and cosmetic dyes, are shown from 1990 to 1979. Annual and cumulated consumption for chromite </) and asbestos are shown from 1990 to 1979. (17 Refs) 213 AU AD TI SI SO LA AC Falk H ; Thomas LB ; Popper H ; Ishak KG Chronic Diseases Div., Bureau Epidemiology, Center Disease Control, Dili ted States Public Health Service, Atlanta, GA, 30333 HEPATIC ANGIOSARCOMA ASSOCIATED WITH ANDROGENIC-ANABOLIC STEROIDS. ICOB/00/92QC5 Lancet; 2(61521:1120-1123 1979 ENG A retrospectlve epidemiological studv of deaths from hepatic angiosarcoma (HAS) in the United States showed that durinq 1969-79 there were 163 such cases, of which 37 (22k) were associated with previously known causes (vinvl chloride, Thorotrast, and inorganic arsenic) and 9 (3.1k) of the remaining 131 cases with the use of androgenic-anabolic steroids. It is suggested that the long-term use of androgenic-anabol1c steroids is the fourth cause of HAS, the majority 0f cases still being of unknown etiology. Moreover, the presented cases serve as a link CO CO o cx -J V. L 00005687 VINYL CHLORIDE PAGE 109 -V V' t-T c Ci '; rtl.-', ! in a spectrum of hepatic disorders recently recognised to be caused by environmental agents such as vinyl chloride, arsenic, and thorotrast, and by contracept1va and anabolic steroids. Similar precursor stages, usually not recognised by clinical laboratory Tests and consisting of areas of hyperplasia of hepatocytes and sinusoidal cells and sinusoidal dilatation, lead potentially to hepatic adenoma, carcinoma, peliosis, and ong1osarco.ua. (Author abstract) (CO Refs) C19 AU AD TI SI SO LA AD HinauT G Service da Pneumologie, CHI de Mont ferine i 1 . 10, rue du General Leclerc, F 93370 Montfermei1, France VINYL CHLORIDE AND POLYVINYL CHLORIDE (LETTER TO EDITOR). ICD3/80/A2509 Nouv Pressa Medt 8(90)13271 1979 FRE Distinction between vinyl chloride and polyvinyl chloride is emphasised in connection with a paper in which the two words were confounded. Polyvinyl chloride contains only inf1niTesimally sm.all Trace amounts of Carcinogenic vinyl chloride, if anv. (1 Ref ) c 220 AU - loprieno N AD - Laboratori a di Genetica, IsTltuTo di AnTropologia Univ. Pisa, Pisa, Italy TI - USE OF YEAST AS AN ASSAY SYSTEM FOP INDUSTRIAL MUTAGENS. SI - ICDB/80/423C3 SO - Chemical Mutagens. Principles and Methods for Their Detection, Hollander A de Semes FJ, ed, New York, Plenum Press, Vol. 5, 3A8 pp., 1979, LA - ENG A3 - The main features of several genetic systems of yeasT that are used to evaluate the mutagenicity of chemical compounds rrs outlined* and recent findings in different compounds are reviewed, A general diagram of the cell cycle of yeast is presented and the advantages of using yeast systems are summarized. The Types of genetic effects produced by methyl methanesulfonate and the comparative mutagenic effects of chemical and physical agents on Schizosaccharomyces pombe are summarized. The use of yeast to detect mutagenic activity in industrial compounds Is discussed with respect to individual compounds. A list of alkylating aqents that have been tested for mutagenicity through the reversion of S pombe to arginine independence is presented. Vmvl chloride monomer is discussed in terms of production of point mutations and gene conversions yeast, in \n^o metabolism, and possible active metabolites ( 2-chicrcacetaldehyde , 2'chloroe thy lene oxide, and 2-chloroethanol ). Styrene and styrene oxide are discussed in Terms of uses, activation by liver microsomal preoaratlons, and mutagenicity and converToqen1c1Ty in yeast. The use of yeast to detect mutagenicity of formaldehyde and tr1chloroethy 1ene is also described. Pesticides and herbicides are discussed in Ter-is of The mutagenicity of individual compounds, The mutagenicity of x co 03 to O oo CO L. C * *W1>1 % -*h<y.IN-Vrx- ' *;:*. `f vx 0000S688 VINYL CHLORIDE PAGE no rC ( ( extracts of plants treated with these compounds, and possible genetic risks. Other compounds that have been evaluated in yeast for possible genetic effects are noted and include the cnrcnium salt of potassium, naphthylamines, and hydrogen peroxide. (53 Refs ) 221 AU - Bolt HM ; Laib RJ ; Stockle G AD - Pharmakologisches Institut car Universitat, Obere Zahlbacher Strasse 67, D-6500 Mainz, W. Germany TI - FORMATION OF PRE-NECPLASTIC HEPATOCELLULAR FOCI BY VINYL BSCMIOE IN NEU3CRN RATS (LETTER TO EDITOR). SI - ICDB/80/41610 50 - Arch Toxicol (Bari); 43:83-34 1979 LA - ENG A3 - In response to an article by Bartsch at al (Arch Toxocol 41, 249-277, 1979) stressing the need for testing the carcinogenic potential of vinyl bromide (VBr ), an experiment in which rats were exposed to 2,COO ppm of vinyl chloride (VC1) or VBr (8 hr/dav, 5 days/wk) for 4-10 wk or 8-15 wk, respectively, is cited, Histochemical evaluation of ATPase-deficient foci m the livers of the rats 2 wk after cessation of exposure revealed that the oncogenic potential of VEr was approx 1/10 that of VC1 . (7 Refs ) 222 AU - Thaler H AD - 4. Medizinische Abteilung, Hilhelminenspital, Montleartstr. 37, A-1171 Wien 15, Austria TI - HEPATOTOXICITY. 51 - ICDB/80/41S75 SO - Dtsch Med Nochenschr; 104(46):1642-1648 1979 LA - GER A3 - Toxic effects manifested in the liver by various drugs and chemicals are reviewed. Hepatotoxici ty is discussed in terms of b i o trains format i on , enzvme induction, covalent binding of macromolecules , hepatic kinetics and liver dan,age, and classification of liver toxins and of liver injuries. A table is presented which summarizes toxic liver damage and Tvpical examples of causes', included are liver cell adenoma caused by ovulation inhibitors, hepatocellular carcinoma caused by aflatoxln B, and angiosarcoma caused bv vinyl chloride monomer. Some aspects and causes of heoa t o t o'-i c l ty which are reviewed in detail include the following: cholestasis, peliosis hepatls, focal nodular hyperplasia, changes characteristic of viral hepatitis, allergic hepatitis, and liver necrosis of the type associated with fulminating viral hepatitis. Different Tapes of liver cancer also are considered in detail. The roiationsmo between the use of oral con tracesti"es or androgens and liver cell adenoma and carcinoma is examined. Adenoma is described with regard to morphology and dlfferen11 a Iion from focal nodular hyperplasia. Studies that relate the use of oral contraceptives To The Incidence of benign liver tumors, liver cell adenoma, and liver cell carcinoma are summarized. The expected frecuercies of occurrence of benign and malignant tumors In women who use oral R&s 139089 c c c c c 23 00005689 VINYL CHLORIDE ( PAGE 111 contraceptives tor grafter than 5 yr are noted. Othan aspects of liver cancer which are briefly discussed include tha mutagenic and carcinogenic affects of active metabolites of aflaToxln B and vinyl chloride monomer. (13 Refs) ( 223 All - Czarnielewski A ; Ki ec-Swi erczynska M J Gluszcz M ; Hoznlak L AD - Dermatological Clinici Medical Acad., Krzemieniecka 5, Lodz> Poland TI - DERMATOLOGICAL ASPECTS OF SO CALLED VIHYL CHLORIDE MONOMER DISEASE. SI - CARC/00/07359 SO - Derm Eeruf U.,vuelt; 27( 9 ): 108-112 1979 LA - ENG AS - Dermatological findings in 30 workers (aged 26-59 yr) who had been in close and continuous contact with various phases of tha vinvl chloride (VC) polymerization process for 2-11 yr are presented, Tha most common abnormalities were histopathologic changes (30 workers)'- history of symptoms of Raynaud's phenomenon (25 workers); positive results in digital piethysmography (29 workers I and in the v1bro-1actila threshold sensory test (29 workers); and scleroderma-1 ike skin lesions (23 workers). Acro-osteolvsis was found in three patients and thrombocytopenia in one. Most abnormalities disappeared or showed signs of healing within 1-2 yr after exposure was discontinued. These results indicate the importance of dermatological examination in detecting the clinical pattern of VC-tnduced disease. (32 Refs) 229 AU - Miller KM ; Herrmann J ; Tomatis L ; Infante P AD - Clinical Epi demiology Oranch, Div. Cancer Cause and? Prevention NCI, NIKi Room A-521, Landow Building, Bethasda, M0, 20205 TI - INTRODUCTION: PERINATAL CARCINOGENESIS. SI - ICD3/30/90950 SO - Natl Cancer Inst Monoqr; (51):3-5 1979 LA - ENG AD - The effects of environmental pollutants (thalidomide, vinyl chloride, dilantin, immunosuppressants, methyl mercury, polvchlorinatad biphenyls, and polybrominated biphenyls) on human fetuses are discussed. IT is suggested that analyses of umbilical cords might lead to greater understandlng of the effects of these pollutants on human fetuses. A general discussion is included. (no Refs) 3D if) q (D 225 AU - Feron VJ ; Spit BJ ; Immel HR ; Kroes R AD - Dept. Toxicology, Central Inst. Nutrition and Food Res. TNC, P. 0, Go* 360 , 3 7C0 AJ Ze t s t, N: tr.ar lands TI - CNE-YEAR TIME-SEGUENCE INHALATION TONICITY STUDY OF VINYL CHLORIDE IN PATS. III. MORPHOLOGICAL CHANGES IN THE LIVER. SI - ICDO/CO/90316 SO - Toxicology; 13(21:193-159 1979 LA - ENG A3 - Morphological changes in tha liver3 of Histar rats exposed to 0 (control) or 5,000 ppm vinyl chloride monomer (VCM) for 9, 13, 26, and 52 wk were investigated. Livers were examined by light c 00005690 VINYL CHLORIDE c PAGE 112 cc and electron microscopy, end engyme Hi s t ochem i cal reactions were measured. The major parenchymal changes included swelling and ( (malformation of the mitochondria, an increase in the amount of Smooth endoplasmic reticulum, necrosis, nuclear and cellular polymorphism of hepatocytes, foci of cellular alteration, neoplastic nodules, and hepatocellular carcinomas. c cGlucose-6-phosphatase activity was reduced in the hepatocytes within the foci of cellular alteration, and alkaline phosphatase had a strong sinusoidal activity. In addition to parenchymal alterations, livers of the VCM-exposed animals exhibited focal dilatation of sinusoids, marked alkaline phosphatase activity of sinusoidal cells, focal proliferation of sinusoidal cells with or without atypia, and multlcentric angiosarcomas containing widely c varying amounts of fibrous tissue. The hepatocytic changes appeared sooner than changes in the sinusoidal lining ceils, suggesting that the hepatic parenchyma may have been attacked by VCM before the hepatic stroma was affected. Further clarification c of the relationship between hepatocytic and sinusoidal cell alterations is necessary. (33 Refs) V. 226 AU - Feron VJ ) Kroes R c A0 - Oapt . Toxicology, Central Inst. Nutrition and Food Res. TNO, P. 0. Box 360, 3700 AJ Zeist, Netherlands (' TI - ONE-YEAR TINE-SEQUENCE INHALATION TOXICITY STUDY OF VINYL CHLORIDE IN RATS. II. H0RPH0L0GICAL CHANGES IN THE RESPIRATORY TRACT, CERUMINOUS GLANDS, BRAIN, KIDNEYS, HEART AMO SPLEEN. SI - ICDB/60/40315 SO - Toxicology; I3(2 ):131-161 1979 LA - ENG J3 0 w AB - The morphological changes in the respiratory tract, ceruminous glands, brain, kidneys, heart, and spleen of Ulster rats exposed to atmospheres containing 0 (control) or 5,000 ppm vinyl chloride monomer (VCM) were investigated. Exposure lasted 7 hr/day, 5 days/wk, for 6, 13, 26, and 52 wk. HlTh the exception of one w CD O CD VCM-exposed female rat who had a squamous cell carcinoma arising from the ceruminous gland, treatment-related pathological changes in organs other than the liver were not observed after A, 13 and 26 wk. A variety of neoplastic and non-neoplastic changes attributed to VCM were observed after 52 wk. In several of the Test animals, hyperplastic and neoplastic alterations of the olfactory epithelium in the nasal cavity were observed; the V hyperplastic chanqe was proliferation of atypical basal cells and cells of Bowman's glands, and the Tumors were highly infiltrative Carcinomas. Lesions observed in the ceruminous glands included papillomas, squamous cell carcinemas, and adeno-squamous carcinomas. Primary tumors were found in the iunqs of Two rats and were identified as a papillary adenoma and a mesenchymal type Tumor. Some Test animals had deformed noses clue to small focal swellings suggestive of nasal tumors, while at least 20 test animals had malignant nasal Tumors. One primary brain tumor was found in the anterior part of the cerebrum. Other brain tumors were observed but ware determined to be metastases from other primary locations. Hemorrhage and inflammatory changes were t ` *'/'* ' '- r ;. *. v"'"v > C (.. 00005691 VINYL CHLORIDE PAGE 113 observed in the lungs of several rats with brain tumors or uith pulmonary metastases from liver tumors. (25 Refs) 27 AU - Hargler LW ; Rogozen M3 ; Ziskind PA ; Reynolds R AD - Science Applications. Inc., Los Angeles, CA TI - RAPID SCREENING AND IDENTIFICATION'OF AIRBORNE CARCINOGENS OF GREATEST CONCERN IN CALIFORNIA. SI - ICD3/80/37221 50 - J Air Pollut Control Assoc; 9(11):1153-1157 1979 LA - ENG AB - A method for establishing a priority list of airborne carcinogens within a state jurisdiction is described. The California Air Resources Board (CA.RB) is sponsoring a three-stage study of airborne emissions of carcinogens. The initial screening procedure identified known or suspected carcinogens most likely to be hazardous to the general population of Californio. The 22 materials identified were ranked by additive and multiplicative algorithms. Criteria used in the ranking procedure included present use and growth in use in California, emission potential, stability in ambient air, dispersion potential, and evidence of carcinogenicity. A nine-member panel of governmental , industrial, and academic scientists also evaluated and ranked the materials. The final selection consisted of 11 substances appearing on at least 2/3 lists and included, in alphabetical order, arsenic, asbesTos, benzene, cadmium, carbon tetrachloride, chloroform, ethylene dibromide, ethylene dichloride, nitrosamines, perchloroethylene, and polycyclic aromatic hydrocarbons. Other highly ranked carcinogenic substances not included on the list were those already subject to established standards (vinyl chloride) or containing substances included on the final list (gasoline, tobacco smoke). In continuing studios, a baseline emissions inventory is being prepared, and a source testing program is being designed. (16 Pets) 228 AU - Kucerova M j Polivkova Z ; Batora J AD - Katedra pediatrie, Institut pro dalsl vzdelavani leKaru a farmaceutu, Budejovicka COO, Frague A, Czechoslovakia TI - MUTAGENIC AND CARCINOGENIC EFFECTS OF VINTL CHLORIDE. 51 - CARC/C0/07526 SO - Prac Lek; 31(6/7 ):2A9-252 1979 LA - CZE AB - The mutagenicity of vinyl chloride (VC) was studied in peripheral blood lymphocytes of nine workers at a polyvinyl chloride manufacturing plant. The workers have been exposed to VC at concontrations of 15-150 ppm for 10-25 yr, Two of three cvtoqenetlc examinations perfc-med o"5r a 2-yr period did not reveal any significant increase in the percentage of cells with chromosome f.berr at l ons compared with that in eight none.'posed controls! the final Test, however, showed a significant Increase in the percentage of cells with chromosome aberrations in three workers (5.2/ vs 1.8/ in the controls). The sister chromatid exchange (SCE ) test was also performed at The time of the Third test: it demonstrated significant increases in SCE frequency In c c c c c 30 R CO CO co o CD to L L 00005692 VINYL CHLCRIOE PAGE 119 5/7 tested workers <15.S'/ vs 9.41/ in the controls). 123 Refs) c 229 AU - Milby TH AO - Div. Scientific and Educational Activities. California Medical Assoc,. 731 Market St.. San Francisco, CA. 99103 TI - VINYL CHLORIDE-RELATED CANCER. SI - CARC/30/07502 SO - West J Med) 130(31:297-298 1979 LA - ENG A3 - Vinyl chloride (VC) has been shown to cause cancer as well as a number of toxic, normalignant diseases in man. There is also some evidence that workers exposed to VC may have an increased frequency of chromosomal aberrations. Angiosarcoma of the liver has been diagnosed in numerous workers exposed to VC, as have CNS tumors (particularly glioblastoma multi forme), long cancer, and cancers of the lymphatic and hematopoietic systems; liver and biliary cancers show a possible association with VC exposure. (1 Ref) c c ( 230 AU - E erndt H AD - Dept. Internal Medicine, County Hosp. with Polyclinic, Meubrandcnburg, E. Germany TI - CURRENT PROBLEMS OF SOLID HEPATIC TUMORS. SI - IC0S/C0/36209 SO - Cask Gastroenterol Vy=; 33(91:220-229 1979 LA - CZE AB - The etiological, epidemiological, and clinical aspects of solid hepatic tumors are reviewed. Correlation between oral conti'acept i on and benign heoa t ocel lular tumors was demonstrated in numerous studies. Significant correlation was found between hepatic cancer and hepatitis D infection in Senegal. Vinyl chloride has been demonstrated as an occupational etiological factor in angiosarcoma of the liver. The incidence of primary malignant hepatic carcinoma is highest in Africa and the Far East, in which aflatoxins are a major factor. The incidence among Afroamoricans is about the same as in American whites, which indicates the etiological role of environmental factors. Ht loss, weakness, loss of appetite, hepatomegaly, and tenderness of the liver are the major clinical symptoms of liver cancer. Patholoqicallv increased aloha-fetooro*eIn levels were found in 33-87/ of the hepatoma patients and in 0-10/ of healthy controls in various studies. Radical surgery is the treatment of choice in hepatoma. (69 Refs I 231 AU AD TI SI SO LA AB - Karlowski K J Uaour H I Jedrych Z - Zaklad Badania Zyunosci i Proedmiotou Ucytku, Panstwowv Zakiad Hiqienv, ul . Choclmska 29, CO-791 Kars aw, Poland - A METHOD FOR THE DETERMINATION OF VINYL CHLORIDE IN PLASTIC MATERIAL U5E0 IN FOOD PACKAGING. - CARC/80/07929 - Roc: Pans t w Zakl Hlgl 30<9 ):371-376 1979 - POL A method for the cetermination of vinyl chloride (VC) and v DO (/) CO to o to CO L L L ' ii C 00005693 VINYL CHLORIDE r PAGE 115 R&S 139094 c polyvinyl chloride (PVC) is reported. PVC is dissolved in Tetrahydrofuran, and the monomer content in The distilled solvent is determined by gas chromatography with flame-ionipation c detection. The recovery rate ranged from 0.05 to 100 mg/kg for VC and from 61V. to 80k for PVC. The detectability index for VC was 0.01 mg/kg of plastic material, (14 Refs) c 832 AU - Sadowski S AD - Zaklad Higieny Komunalnej , Pantswowy Zaklad Higieny, ul. C Chocimska 26, 00-791 Warsaw. Poland TI - DETERMINATION OF LOW CONCENTRATIONS OF VINYL CHLORIDE IN THE AIR. SI - CARC/S0/07626 SO - Rocr Pans Tw Zakl Mg) 30(6):613-919 1979 ( LA - POL A3 - A method for The determination of low concentrotions of vinyl chloride In the air is reported. The method is based on the adsorption of vinyl chloride on activated charcoal followed by ( de-absorption of the carbon with carbon disulfide. Vinyl chloride is then determined by gas chroma togrr.ohy and a f lame-i oni cat i on ( cdetector. The limit of detection of the method is 0,1 ng vinyl chloride, (16 Refs) c 233 AU - Hopkins J AD - Ho affiliation given TI - VINYL CHLORIDE--PART 1= META30LISM. SI - CARC/30/07396 50 - Food CosmoT Toxicol) 17(6)1603-605 1979 LA - ENG AB - The metabolism of vinyl chloride (VC) is reviewed. The metabolism of VC administered to rats by various routes appears To be dose-related, the major urinary metabolites belnq N-acety1-S-(2-hydroxyethy1 leysteine. N-acety1-S-vinylcysteine, and thiodiglycol1lc acid, ChioroaceTlc acid does not appear To be a major VC metabolite. A cytochrome enayme is involved in the formation of the active metabolites, and there appears to be only a single saturable metabolic pathway for VC in the rat. 112 Refs) 2 36 AU - van Li crop JO AD - Keuringsdients van Waren, Utrecht, Netherlands TI - SUBSTANTIAL REDUCTION IN THE LEVELS OF CARCINOGENIC SUBSTANCES IN FOOD PACKAGING MATERIALS. 51 - CARC/O0/O7579 SO - Vccdings tliddelen Technol) ICt 111:29 1979 LA - DUT AG - The vinyl chloride residue level in food packaging materials has decreased substantlally from 127 ppm m 1976 to 77 ppb in 1978 in the Netherlands. The max allowable vinyl chloride concentra11 on in food is 10 ppb. (no Refs) L L 00005694 VINYL CHLORIDE PAGE 116 235 AU - Bint-13 CH AD - Hadical Centre* BP Oil Ltd., BP Housa, Victoria St., London, 5U1E 5MJ, England TI - VltiYL CHLORIDE ' A REVIEW. SI - IC0B/60/36154 SO - J Soc Occup Kadi 29(4)1134-141 1979 LA - ENG AB - The chronology of events loading to the association of vinyl chloride uith acro-csteoiys1s and with angiosarcoma of the liver is outlined, and the epidoniioloqic.il, chemical, hi stopathological, and biochemical investigations that resulted are reviewed. Clinical manifestations of vinyl chloride exposure are acro-osteolysIS, angiosarcoma of the liver, hepatic fibrosis, pulmonary adenomas, cerebral neuroblastomas, mutagenicity, chromosomal aberrations, embryotoxicity, and teratogenicity. The metabolism of vinyl chloride and possible mechanisms of action which would account for the clinical effects are discussed. (50 Refs ) c c c c c 236 AU - Falk H ; Thomas LB ; Popper H ; Ishak K AD - Center for Disease Control, Atlanta, GA TI - HEPATIC ANGIOSARCOMA ASSOCIATED UITH USE OF ANDROGENIC-ANABOLIC STEROIDS (MEETING ABSTRACT). SI - IC03/79/35753 SO - Gastroenterologyi 77(5):A11 1979 LA - ENG AB - A retrospective epidemiologic study of deaths from hepatic angiosarcoma in the United States in the period 1964 through 1974 identified 168 cases) of these, 37 (22X) were associated with previously known causes (vinyl chloride, Thorotrast, and inorganic arsenic). Of the remaining 131 cases. 4 (3.IX) were associated uith the use of andrcqenic-anabolic steroids; available druq use data suggest that this proportion is higher than expected. It is postulated that the long-term U3e of androgenic-anabolic steroids is a fourth cause of hepatic anqiosarcoma, with the majority of cases still of unknown etiology. Moreover, tile presented cases serve as a link in a spectrum of hepatic disorders recently recognised to be caused by env i ronment al agents such as vin'-l chloride, arsenic, and Thorotrast, and by contraceptive and anabolic steroids. Similar precursor stages, usually not recognised by clinical laboratory tests, consisting of areas of hyperplasia of hepatoevtes and sinusoidal calls and sinusoidal dilatation lead potentially to hepatic adenoma, carcinoma, peliosis, and angiosarcoma, (no Refs) 30 to w CD o CO 07 c L L 00005695 VINYL CHLORIDE PAGE 117 237 AU - Bognar Z Czeizel E ", Szentesi I AD - Schopf-Merei Korhaz e3 Anyavedelmi Kozpont, Orszagos Kozegeszegugyi Intezet. Hungary TI - EPIDEMIOLOGICAL STUDY OF THE REPRODUCTIVE FUNCTION IN PVC WORKERS. SI - CARC/79/07174 SO - Orv HaTil; 120(30);1819-1021 1979 LA - HUN AB - An epidemiological study of the families of 231 Porkers exposed to polyvinylchlorida (PVC) or vinyl chloride showed an increase in the frequency of miscarriage, intrauterine death, and congenital anomalies (eg, spina bifida) in the families of workers exposed to vinyl chloride compared with families of nonexp03ed controls and families of workers exposed to PVC. (20 Refs ) c c c c 238 AU - De Meester C ; Duvarqor-Van Bogaert M Lambotte-Vandepaer M AU - Roberfrold M I Poncelet F J Mercler M AD - Lab. Biotoxicology, Sch. Pharmacy, Univ. Louvain, U.C.L.-73.69, B.1200 Brussels, Belgium TI - LIVER EXTRACT MEDIATED MUTAGENICITY OF ACRYLONITRILE. SI ICDB/79/34490 SO Toxicology; 13(1):7-15 1979 LA ENG A3 The mutagenic effect of acrylonitrile (ACN) vapors on Salmonella typhimurlum and the enhancement of mutagenicity by liver pos tin i tochondr i al fractions were studied. Adult rats and mice wore pretreated as follows: daily ip injection of diethylmaloata (DEM), arochlor (A.RO), phenobarbi tal ( PB), 3-methylcholanthrene (3-MC), acrylonitrlle (ACM), or styrene (STY); inhalation of vapors of butadiene (BUT), vinyl chloride (VCM), or vinylidine chloride (VDC); and consumption of drinking water containing FB. The livers were removed, homogenized, and centrifuged to obtain the postmiTocnondrial fraction 59. Microsomes P/9 and cytosols S/10 were added to the mix at tha same concentration as S9I the P/4 mix was further supplemented with glucose-6-phosphate dehydrogenase. S typhimurlum strains TA 1530 and TA 1538 were incubated for 1 hr in the presence of ACN after the addition of S9, P/4, or S/10. The numbers of his+ revertant colonies were calculated. The liver postmlTochondrIal fractions from mice had a more pronounced effect on the mutaqenlclty of ACN Than did Those from rats. PretraatmenT with DEM, F3, or ACN decreased the mutagenicity of ACN when the S9 fraction was obtained from rats and increased the mutagen Icitv of ACN when The 59 fraction was obtained from mice. Pretreatmont with STY, VCM, VDC, BUT, and 3-tlC increased The mutagenicity of ACN when S9 was obtained from both rats and mice. Pretreatment did not affect the protein concentrat 1 ons of the various 59 fractions', within the range of 59 conccntrat1ons used 130-240 ul 5,/plate), the number of nis+ revertanTs/plate increased with The protein concentrat1 on. The reversion rate was unaffected by the addition of valeric acid (S'/.F 525A) or by inactivation of cytochrome P450 by previous incubation of the 59 mix with carbon monoxide. In contrast, The c 30 C/) W <> O <D CT) C. l L L 00005696 VINYL CHLORIDE PAGE 113 239 AU AD TI SI SO LA AB 290 AU AD TI SI SO LA AB mutagenic effect of ACN war completely inhibited by The addition of meTyrapone cr by boiling the S9 mix. The results suggest That the cytochrome P950-dependent monooxygenases do not play a major role in the metabolic activation of ACH into a mutagenic intermediate. (19 Refs) Pcncelet F j De Msester C ! Roberfroid M ! Mercier M Lab. Biotoxicology, Sch. Pharmacy Brussels. Belqium INFLUENCE OF EXPERIMENTAL FACTORS CN THE MUTAGENICITY OF VINYLIC MONOMERS (MEETING ABSTRACT). ICD3/79/33771 21st Congress of the European Society of Toxicology held in Dresden. E. Germany, 11-13 June 1979. European Society of Toxicology:. 199 pp.. 1979. ENG The mutagenicity of several vinylic monomers such as styrene, butadiene, acrylonitrile. and vinyl chloride was evaluated with the Salmonella typhimurium test system in various experimental conditions: The classical plate Incorporation method, incubation in liquid medium, exposure in gaseous atmospheres or a bacterial fluctuation test. Morever. assavs mere performed in the presence of different metabolic activating systems: liver pos t-mi tochondr i al fractions, liver' purified microsomal fractions obtained from variously pretreated animals of different species (rats, mice, etc)', morever, the protein content of the suspensions util iced as enqyme sources uas varied. The results obtained clearly demonstrate that all These experimental parameters have a verv profound and variable effect on The mutagenic potency of these monomers. The magnitube of The modification seems to be frequently correlated ui th the physico-chemical properties of the monomer assayed. (1 Ref) Leipolc-Anqermuller S ! Wegener K No affiliation given DOUBLE TUMORS OF THE LIVER FOLLOWING INTRAVENOUS INJECTION OF THCROTRAST (MEETING ABSTRACT). ICDD/79/33572 Zentralbl Allg Pathol! 123(3):270 1979 ENG The rare simultaneous existence of a cholanqio-cellular carcinoma (CCC) and a hemangi oendothel i osarcoma (tleSA) in each of two patients uiho had previously received iv injections of Thcrotrast is reported. Thirty-five vr after Injection of Thorotrast, a man developed infiltrating CCC uith,metastases to the lung and adrenal gland. Single polymorphic and hvpochromatic cells uere distributed in The wall of a hvperemic and dilated sinus. Similar prol1feraTions of polymorphic and hypochronaIic cells have been seen in the early stages of development of HeSA in workers -.no have been exposed To wlnvl chloride. The patienT died of tumor-1nduced shock at the ace of 63 \'r, A woman developed a nonmetajtas Ic1ng CCC and an infiltrating, destructive HeSA showing similarities to The areas containing the aberrant sinus-pa 11 cells in The first patient. Other areas resembled c c c c 7J If) CaJ to o to 'U L L 00005697 VINYL CHLORIDE PAGE 119 291 AU AD TI 51 SO LA AD 292 AU AD TI SI SO LA AB small pools of blood, but most contained a network of tumor cells with various types of atypical cells. The woman died at the age of 97 yr in hypovolemic shock. Tnorotrast Was not found in either the proliferating sinus-wall calls or in the HeSA tumor cells. (no Refs ) Roosken AA Dlenst Centraal Milieubeheer Rijnmond, Schiedam, Netherlands MEASURING ORGANIC GASES AND VAPORS IN THE AIR. ICDB/79/32909 Polytech Tldschr Proces techni ek'> 39(7)1909-915 1979 DUT The measurement of organic gases and vapors in the atmosphere Is described, and the problems of air pollution caused by organic emissions in South Holland are outlined. Considerable amounts of vinyl chloride, benzene, and aerylonitrile are emitted from in an industrial area in South Holland. Measuring the total amount of hydrocarbons is the simplest method To determine organic gases and vapors in the air. The individual components can be identified by the combination of mass specTrcmetry with capillary gas chromatography, or by determining the retention time. Vinyl chloride can be determined by gas chromatography. (15 Refs) Aune T Mi 1jotoksikologisk avdeling, Statens Institutt for Folkehelse, Oslo, Norway CARCINOGENIC CHEMICALS IN THE ENVIRONMENT. CARC/79/06919 Kjemi ; 39(5)-`25-29 1979 NOR Recent studies on enyironmental carcinogens are reviewed. The chemical substances known To be carcinogenic in humans include aflatoxins , 9-aminobiphenylI arsenic compounds, substances occurring in the synthesis of auramine, benzene, benzidine, bis(chlcromethyl ) ether, cadmium, chloramphenicol, chloromethyl methyl ether, chromium, cyclophosphamlde, d1ethylst1lbesTrol, isopropyl oils, Melphalan, mustard gas, 2-naphthylamine, nickel, N, N-b i s ( 2-chi oroe thy 1 ) - 2-nap'n thy 1 am i ne , oxyme 1 hoi one , phenace tin, soot, tar, and vinyl chloride. The mutagenicity of cigarette smoke condensate cannot be explained with the presence of benzopyrene and nitrosamines alone. There are strong indications that the pyrolysis products of proteins and amino acids Contribute subsTantIally To the mutagenic effect. If cannot be ruled out that such cocarclnogens as harman and norharman also play an important role. Chemically irduced cancer is dose-dependent , Though The dose-response relationship for humans is not yet known for the cancertrat1ons that are relevant for human exposure. The fact That a chemical induces cancer in animals or .Mutations In other test systems is not always sufficient substantiation for Tr.e ban of that substance. (6 Refs) 33 C/3 w CO O <> 00 c c L e 00005698 VINYL CHLORIDE PAGE 120 293 AU - Jukes TH AO - Univ. California, Berkeley, CA, 99709 TI - DDT AND CANCER. SI - CARC/79/06899 SO - Clin Toxicol; 19(91:961-963 1979 LA - ENG AB - The claim That DDT exposure causes cancer is dispuTed, DDT feeding in rats for 2 yr (most of The rat lifespan) results in a minimal hepatocarcinogenic tendency. Liver changes identical to those produced by phenobarbital, pyrethrum, and other chemicals were seen 19 wK after DDT feeding in rats and could be produced in rabbitst mice and guinea pigs, but not in chickens, decs, cats, and monkeys or large domestic animals. In another study, no tumors were found in Three generations of dogs (greater Than 500 animals) raised on diets containing high DDT doses. Factory workers in DDT production and man who have been involved in spraving DDT for many years have shown no indication of DDT causing cancer. This is in marked contrast to other industrial careinegons , including asbestos, arsenic, vinyl chloride, and dimethylchlorether. According to the World Health Organication, extensive medical tests of 150 persons wlTh prolonged occupational exposure to large doses of DDT have not revealed any related findings except increased storage and excretion of DDT and its metabolites and mild stimulation of hepatic microsomal encymes. (no Refs) c c c c c c 299 AU AD TI 51 SO LA AB Reitz RH ; Quasi JF ; Watanabe PG J Gehring PJ Toxicoloqy Res. Lab., Health and Environmental Sciences, U.5.A., Dew Chemical U.S.A., 1803 Building, Midland, Ml, 9S690 CHEMICAL CARCINOGENS: ESTIMATING THE RISK (LETTER TO EDITOR). ICD3/79/31810 Science; 205(9912 ):1206-1208 1979 ENG Although it is believed to be possible that thresholds for chemical carcinogens exist, research on vinyl chloride has not provided evidence showing such thresholds. Attempts to provide irrefutable evidence of absolute thresholds for chemical carcinogens are viewed as futile. Moreover, it is emphasized that risk assessment should be tested against real work related data when ever possible. (11 Refs) 30 fio CO co ID o (D (> 295 AU AD TI SI 50 LA AB Hesbert A ; Cavelier C I Bottin MC I Lemonnier M InsTltut National do Recherche et de Socurite, avenue de Bourgogne, B.P. no. 27, 59500 Vandoouvre-lcs-Nancy, France MUTAGENIC EFFECT OF A CHEMICAL CN BACTERIAL STRAIN OF SALMONELLA TY Pi II MUR I UN (AMES TEST): METHOD AND RESULTS FOR SEVERAL Ki.'CN.N CARCINOGENS. CAPC/79/06750 Arch Mai Prof! 90(3/9 ):937-957 1979 FRE The mutagenicity of known chemical carcinogens was tested using the Salmonella typhimurium strains TA 98, TA 100, TA 1538, TA c c c ( c'"* -.^V' w '7%-CS;. a C ( 73 8 W co to --l o 00005699 VINYL CHLORIDE PAGE 121 1535, TA 1537i and TA 1530, with and without metabolic activation by rat hepatic microsomal fraction. Ame3 test results were considered positive if the number of revertants per dish exceeded double the number of spontaneous revertants. All substances tested (2-aminofluorene> 2-acetylaminofluorene> 9-aminoacridine, 1-aminoanthracene> 2-aminoanthracene, dibenzo(a,i ipyrene, benro ( a Jpyrene , 3-methylcholanthrene , chrysene, 7,12-dimethylbenzla )anthracene> 9-nitroqut noline-l-oxide, N-mathyl-N'-nitro-N-nitrosoguanidine, me thylmethane sulfonate, sodium azide, aflatoxin SI, and vinyl chloride were found to be mutagenic, both with and without metabolic activation. (19 Refs) 296 AU - Pilichowski P ; Faure C ; Aubert M i Pahn M ; Latreille R AU - Barrie J AD - Service de Chirurgie Thoracique. Hopital des Sablons, F 33700 La Tronche, France TI - ANSIQ54RCCMA OF THE RIBS ASSOCIATED WITH POLYVINYL CHLORIDE INTOXICATION. SI - ICD3/79/30992 SO - Nouv Presse Ned; 8(30)=2985 1979 LA - FRE A3 - A 38-yr-oId man, who had worked rn.mv years in a vinyl chloride factory, presented with a 9-mo history of left thoracic pain. Radiography showed an area of lysis on the posterior arch of the fifth rib and on the seventh dorsal vertebra (without associated spondvlodiscitis ). The patient underwent surgery (excision of the posterior arches of the 9th, 5th, and 6th ribs ). A diagnosis of angiosarcoma, beginning to invade the soft tissues, was made. Scintigraphy and angiography revealed a malignant tumor in the right lobe of the liver. Two mo after surgery, lysis of third left rib was observed. The patient died 2 mo later, after Suffering hemorrhaq1c collapse (rupture of the hepatic tumor) and right hepatectomy. (9 Refs) 297 AU - Powel1-Jackson P I Davis H AD - Liver Unit, King's Coll. Hosp., Denmark Hill, London, England TI - OCCUPATIONAL LIVER DISEASE. SI - ICDB/79/29907 SO - Practitioner ; 223(1333)167-70 1979 LA - ENG AB - Occupational hepatotoxins are classified according to the nature of the liver injury that each causes. Acute hepatocellular injury is caused by carbon tetrachloride, tetrachloroethane, toluene, Trichloroe thylene , 2,Zbis(p-chlorophenyl )-l,l,l-trlchlore thane, triniIrotoluene, ionizing radiation, hepatitis 3 virus, and halothane. Granulomatous hepatitis is caused by beryllium, and hepatic fibrosis and malignancy are caused by vinyl chloride monomer. (39 Refs) c c c ( c c c e L L 00005700 VINYL CHLORIDE PAGE 122 243 AU - Pessayre D ; Wandscheer JC ; Descatoire V ; Artigou JY AU - Benhamou JP AD - Units ds Recherches da Physiopatnologi e Hepatique, Hospital Beaujon, 9211S Clichyi Franca TI - FORMATION AND INACTIVATION OF A CHEMICALLY REACTIVE METABOLITE OF VINYL CHLORIDE. SI - ICDB/79/29519 SO - Toxicol Appl Pharmacol! 49(3)1505-515 1979 LA - ENG AB - Ths metabolic activation of vinyl chlorida by hepatic microsomal mixed-function oxidase system into chemically reactive metabolites that 1) covalently bind in vitro to microsomal proteins, 2) covalently bind in vivo to tissue proteins, and 3) may destroy hepatic cytochrome P-450 and deplete hepatic glutathione was studied in both non-Treated and in variously treated male Sprague-Dawley rats. When the rats were exposed to a 5X vinyl chlorida atmosphere for 18 hr, the hepatic microsomal cytochrome P-450 decreased linearly with time; the decrease uas negligible in rats treated with cobalt chloride (CoCl2), but higher in phenobarbital-treated rats. 14C-vinyl chloride administration resulted in irreversible radioactive binding to whole tissue proteins: binding to blood, kidney, and spleen proteins was about 33X of that to liver proteins; CoCl2 reduced binding in all organs tested. When 14C-vlnvl chloride was incubated with hepatic mtcrosomes and the NAOPH-regenerating system, radioactive binding to microsomal proteins was detected, whereas no binding occurred with microsomes from blood, kidney, Spleen, or muscle. No binding to hepatic microsomal proteins uas detected in the absence of the NADFH-regenerating system or in the presence of 90X carbon monoxide-1 OX oxygen atmosphere or SKF 525-A, In vitro binding To hepatic microsomes was decreased by glutathione or cysteine, but not S-methyl glutathione or glycine. Addition of the compound 1,1,1-trichioropropene 2,3-oxide (TCPO) To the incubation mixture increased in vitro binding to microsomes; and whereas binding was increased by only 37X in control rats, it was increased by 134 and 200X in phenobarbital treated rats, respectively. (28 Refs) 249 AU AD TI SI SO LA AB Maltoni C Inst. Oncology, Tumor Center, Bologna, Italy PERSPECTIVES ON ENVIRONMENTAL AND OCCUPATIONAL ONCOGENESIS OF CNS (MEETING ADSTRACT). ICD3/79/2 92 93 International Symposium on Multidiscip1inary Aspects of Brain Tumor Therapy. Abstracts of a Symposium held in Orescia, Italy, 8-10 June 1979. To be published bv E1sevier/NorTh-Hol1 and Biomedical Press, Amsterdam, 156 pp., 1979. ENG Tumours of CHS in humans have not been correlated in the oast with environmental oncogenic factors, the only available data, before 1970, were the results of an epidemlological investigation indicating an excess of CMS tumors among workers in the rubber 00005701 VIHYL CHLORIDE PAGE 123 c and plastic industries, in Ohio, the center of the United States rubber industry. In recent yr, the hypothesis of possible c environmental origin of CHS as well as of other neurogenous tumors has been growing on the basis of three sets of results. 1) Vinyl chloride, one of the most important compounds in the plastic industry, given by inhalation, produces encephalic neurobiastoi.ias in rats. Parallely, a fivefold incidence of brain ( neoplasias has been reported among workers heavily exposed to this monomer. 2) Acrylonitrile, another very important compound in plastic industry, administered by ingestion and by inhalation, causes CHS gliomas in rats. 3) Bis(chloromethylJether, administered by inhalation, produces in rats esThesioneuroepitheliomas. On the basis of these recent findings. The following conclusions can be reached'- 1) CHS tumors may be environmental in origin; 2) The possible carcinogenic effects on the CHS of known and suspected carcinogens must be better explored, both experimentally and ep i dem i ol og i cal ly3) more basic research in experimental animals should be performed, with particular regard to natural incidence of CHS tumors, (no Refs) 250 AU - Bartsch H i Sabadie N I Halaveille C ; Camus AM ; Brun G AD - Unit Chemical Carcinogenesis, International Aqcncy Res. Cancer, 69006 Lyon, France i TI - TISSUE SPECIFICITY IN METABOLIC ACTIVATION. SI - CAPC/79/06076 SO - Adv Pharmacol ChemoTher; 9:93-102 1979 LA - ENG AB - A model for The organospecificity of chemicals is proposed based on data from several systemicallv acting carcinogens: N-nitrosamlnes, N-(alpha-acyloxvJalky1-N-alkvlniTrosamines, and 3,3-d ime thy 1-1-phenyl tr'i azene . The organ specificity of certain carcinogenic chemicals can be determined by The half-lives of their ultimate carcinogens, which may act to prevent their distribution in the bodv by covalent reactions in the organs (cells) in which They are generated. In human liver, large interindividual differences in the activity of carc1nogen-activating enzymes were noted. Aryl hydrocarbon-hydroxylase (AHH) activity and microsome-mediated mutagenicity were measured using the hepatocarcinoqens N-n 1 ti-osomorphol i ne , H-n I t r oso-N ` -me t hy lp i peraz i ne , and vinyl chloride as substrates. When AHH activity In liver specimens from hu,,'an subjects was plotted against The respective microsome-mediafed mutagen1cItv for 5almcnella typhimur1um, a positive correlation was obtained for the rate of oxidative benzol a Ipyrene metabolism and mutagenIc1ty in the presence of all three substrates. Thus, differences In Tissue-specific activation processes of chemical carcinogens appear to be contributing factors in the production of tumors on In certain organs and may also condition the carcinogenic response In different individuals when thov are exoosed to the same level of envjronmental carcinogens. (39 Refs) 00005702 VINYL CHLORIDE PAGE 124 251 AU - Henschler D i Borise G AD - Inst. Toxicology, Univ. Wurzburg, D-8700 Wurgburg, W. Germany TI - METABOLIC ACTIVATION OF CHLORINATED ETHYLENE DERIVATIVES. SI - CARC/79/06075 SO - Adv Pharmacol Chemotheri 9:123-130 1979 LA - ENG AB - The chlorinated ethylenes (CE) were studied to determine the structural requirements Tor their oncogenic effects. The eooxides of all CEs except 111-dichloroetnylene oxide uere prepared, and the in vitro rearrangement mechanisms were studied. The eooxide rearrangement products were either chlorinated aldehydes or acyl chlorides. The metabolites excreted in vivo, chlorinated ethanols and acetic acids, can be derived from the epoxide rearrangement products. Trichloroethylene was an exception! its epoxide rearranged in vitro to dichloroacetyl chloride, whereas the metabolites are oxidation or reduction products, respectively of trichloroacetaldehyde. In vivo, trichloroethylene epoxide is converted, via the Trivalent iron of cytochrome P450, at The site of formation In the hydrophobic phase to chloral. In a modified Ames test system using Escherichia coli K 12, vinyl chloride, vlnylidine chloride, and trlchloroethylene exerted mutagenic activity after activation by induced liver mtcrosomes. The tetraand 1.2-dichloroethylenes (cis and trans ) were inactive in this system. A molecular rule derived from these findings states that unsymmetric chlorine substitution induces, by an imbalanced electron withdrawing effect, The epoxides To become highly electrophi1ic, this being a prerequisite for mutagenicity and carelnogenicity . (13 Refs) 252 AU - Sullivan FM ! Barlow SM AD - Dept, Pharmacology, Guy's Hosp. Medical Sch., St. Thomas ST., London SE1 9RT, England TI - CONGENITAL MALFORMATIONS AND OTHER REPRODUCTIVE HAZARDS FROM ENVIRONMENTAL CHEMICALS. SI - CAHC/79/06037 SO - Proc R Soc Lond [Biol]! 205(1150):91-110 1979 LA - ENG AB - Possible adverse effects of chemical exposure on reproduction are discussed, and data concerning the reproductive outcome after exposure to chemicals in the workplace or environment are reviewed. Exposure of men to environmental chemicals mav lead to cancel' in their oftsprinq! a study of 386 children dying from malignant disease before less than 5 yr of age showed a significant excess of fathers in hydrocarbon-related occuoation3. The association between vaginal cancer and prenatal dieThyIstilbestrol exposure has been established. Angiosarccmas have been reported in offspnnq of pregnant rats exposed to vinyl chloride monomer. Other possible transplacental carcinogens include anesthetics and Irradiation. (103 Refs) w-Y- .13 ( 00005703 VINYL CHLORIDE PAGE 125 v> <a//. c c j -*--w'^ I r . AjiSjfc 253 AU - Frejaville JP ; Beaune P ; Cresteil T AD - Departement d'AnasThesiologie, Hopltal Necker, 49, rue de Sevres, 75015 Paris. Franca TI - METABOLISM OF CHL0R0ETHYLENES. SI - ICDB/79/26806 SO - Arch Mai Prof, 40(1/2)=359-364 1979 LA - FRE AB - Currant data on the human metabolism of trichloroethylene and vinyl chloride are reviewed. The metabolic pathways and potential careinogenicity of their degradation products are discussed, and their replacement by tetrachloroethylene or 1,2-dichloroethylene is advised. (4 Refs) 254 AU - Harrison EA AD - Natl. Technical Information Service, Springfield, VA TI - TOXICITY OF VINYL CHLORIDE (A BIBLIOGRAPHY WITH ABSTRACTS). SI - ICOB/79/26302 SO - Toxicity of Vinvl Chloride (A Bibliography with Abstracts). This Title Available Through National Technical Information Service, Springfield, Va., as NTIS/PS-79/C419/6GA:, NTIS/PS-79/0419, 91 pp., 1979. LA - ENG A3 - Research is cited on the health hazards from exposure to vinyl chloride and vinyl chloride resins. Studies are included on the epidemiology of industrial and public exposures to the compound and its degradation and combustion products. (Author abstract) 255 AU - Laib RJ I Stockle G t Bolt HN ! Kune W AD - Institut fur Toxikologie, Universltat Tubingen, Wihelmstrasse 74, D-7400 Tubingen, W. Germany TI - VINfL CHLORIDE AND TRICHLOROETHYLENE: COMPARISON OF ALKYLATING EFFECTS OF METABOLITES AND INDUCTION OF PRENEOPLASTIC ENZtHE DEFICIENCIES IN RAT LIVER. SI - CARC/79/05316 SO - J Cancer Res Clin Oncol; 94(2)1139-147 1979 LA - ENG AS The extent of alkylation of nucleic acid bv metabolites of trichloroethy1ene (TCE ) and vinyl chloride (VC) was compared, along with the induction, by TCE and VC, of preneoplastic foci deficient in nucleus 1de-5-Triphosphatase in newborn Wistan rats. (1,2-14C)VC and (1.2-140 TCE were incubated with rat liver mlcrosomes, MADFH, and yeast RNA. TCE metabolites were irreversibly bound to proteins in microsomal incubations to a higher extent than VC metabolites, but irreversible bindinq to RNA IMS lower for TCE metabolites. Hyd-olysis of the RNA that was reisolated from microsomal incubations with 14C-VC or 14C-TCE and separation of the nucleosides showed different alkylation products arising from VC and from TCE. 1,N(6 )-Ethenoadenos1ne and 3,N(4 )-ethenocytidine were produced only with 'metabo1ites of VC, possibly through The formation of an imidazol ring. The different reactivities of VC and TCE metabolites prompted a comparison of Tre oncogenic effects of both compounds in rat liven cells. c c c c JO c/> w <o o 4* C L e L 00005704 VINYL CHLORIDE c PAGE 126 Newborn rats were exposed for 10 wk To 2,000 ppm VC or TCE 8 hr/day> 5 days Aik. After this period, livers of the animals were stained for nucleoside-5-triphosphatase. The VC-exposed rats showed focal hepatocellular deficiencies in this enzyme, which are supposed to represent an early sign of malignancy! no such changes were induced by TCE exposure. The data Therefore suggest differences between the activity of VC and TCE in The rat liver. (24 Refs ) 256 AU - Zimmerman HJ AD - Veterans Admin. Medical Center, 50 Irving St., N.W., Washington, DC, 20422 TI - DRUG-INDUCED CHRONIC HEPATIC DISEASE. 51 - CARC/79/05660 SO - Med Clin North Am! 63(3)1567-582 1979 LA - ENG AB - The induction of chronic active hepatitis, subacute hepatic necrosis, steatosis, phospholloidosls, vascular hepatic lesions, hepatic granulomas, cirrhosis, noncirrhotic portal hypertension and neoplasms by various drugs is reviewed. The relationsnips between liver adenoma or carcinoma and oral contraceptives and between hepatic angiosarcoma and vinyl chloride or Thorium dioxide exposure are discussed, (75 Refs) 257 AU - Daneshmend TK ! Scott GL ! Bradfield JW AD - Bristol Royal Infirmary, Bristol BS2 6HW, England TI - ANGIOSARCOMA OF LIVER ASSOCIATED WITH PHENELZINE. SI - CARC/79/05635 SO - Sr Ned J! 1(6179)11679 1979 LA - ENG AB - A case of liver angiosarcoma in a woman who had taken phenelzine for at least 6 yr (45 mg/day for The first 3 yr, 15 mg/day thereafter) is reported. There was no hisTory of exposure to thorium dioxide, arsenic, or vinyl chloride. An osteolytic area suggestive of metastatic disease was present in the lateral epieondyla of the right humerus. Phenelzine administration increases the incidence of angiosarcoma in female mice, suggesting a possible etiologic relationship in this patient. (4 Refs ) 253 AU AD TI SI SO LA AB - Gehrmq PJ ! Watanabe PG ! Park CN - Toxicology Res. Lab., Dow Chemical, Midland, MI, 48640 - RISK OE ANGIOSARCOMA It) WORKERS EXPOSED IN VINYL CHLORIDE AS PREDICTED FROM STUDIES IN RATS. - CARC/79/05599 - Toxicol Appl Pharmacol! 49(1)115-21 1979 - ENG - Dos e-response data for the induction of angiosarcoma in rats exposed to various levels of vmvl chloride (VC) together with attendant biotransformaTlon data were used To estimate the risk of developing angiosarcoma in pe-sons exposed to VC. Since a biotransformation product of VC, not VC per se, is responsible for the induction of angtosarcc -a, the body surface area of c c c c l. 30 R U) W CD _l O cn c c L L 00005705 VINYL CHLORIDE PAGE 127 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 modeli 10 hepatic angiosarcomas were predicted to occur in a recently reported epidemiological cohort of 9677 workers; in actuality five have occurred. Linear models and a model based on the equation, Risk = l-e(-betax), where x = dose, do not appear as reliable. For an S-hr day, 5 days/week, 35-year time-we 1qhted-average exposure of 1 ppm, The predicted incidence of hepatic angiosarcoma using the prebit model is 1.5 X 10(-S). (16 Refs) 259 AU " Coustou F AD - Univ. Bordeaux II, Bordeaux, France II - CARCINOGENIC RISK OF PRODUCTS USED IN THE PHARMACEUTICAL AND RELATED INDUSTRIES. SI - CARC/79/05397 SO - IARC Sci Fubl; (25 ):129-1A9 1979 LA - ENG AB - Tiie problems, in France, of regulating drugs to eliminate or curtail potential carcinogen!citv are reviewed. Some carcinogens may be introduced during the manufactunng process, such as asbestos during filtration, vinyl chloride in aerosol production or packaging, or 2-naphthylamine and other aniline compounds during the dyeing process. The use of artificial sweeteners in The manufacture of foodstuffs is banned in France. At present, general regulations of the French government for the pharmaceutical industry state that agents should be tested for careinogeniclty prior to marketing only if: (1) the agent is closely analogous to known carcinogens cr cocarcinogens! (2) a suspicion of carcinogenicity has been aroused during lonq-Term toxlcological Testing; (3) the drug is to be administered over long periods of Time. (22 Refs) 260 AU - Drevon C ; Kuroki T AD - Unit Chemical Careinoqenesis, International Agency Res. Cancer, 150 tours Albert Thomas, 69372 Lyon Cedex 2, France TI - MUTAGENICITY OF VINYL CHLORIDE. VINYLIDENE CHLORIDE AND CHLOROFRENE IN V79 CHINESE HAMSTER CELLS. SI - CARC/79/053A1 SO - Mutat Res; 67(2 ):173-102 1979 LA - ENG AD - The mutagenicity of vinyl chloride (VC), vinylidene chloride (I>1-dichloroethylone: VDC) and chlorcprene ( 2-chioro-1,3-but Tad i cue ) was tested in V79 Chinese hamster cell3 in The presence of a 15,000 x g liver supernatant from phenobai'b i t a 1-pro tr'ea t ed rats and mice. Nutations in terms of 6-araquanine and ouabain resistance wore Induced in a dose-related fashion by exposure to VC vapor in the presence of the liver supernatant from ohenobarb I tal -pre treat ed E5DVI rots. VDC and chloroprene vapors induced a dose-related toxicity when Tested with the rat liver supernatant, but These two compounds were not mutagenic In V79 cells under The assay conditions. The results are discussed with regard To The metabolic activation of R&S 139106 00005706 VINYL CHLORIDE PAGE 126 c the compounds and to the correlation between the carcinogenic!ty of VC in humans and experimental animals. (31 Refs) c 261 AU - Stockle G I Laib RJ I Filser JG ; Bolt HM c AD - Institut fur Toxikologie, Universitat Tubingen, Wi lhelmstrasse 56, D-7900 Tubingen-1, W. Germany c cT X - VINYLIOEHE FLUORIDE: METABOLISM AND INDUCTION OF PRENEOPLASTIC HEPATIC FOCI IN RELATION TO VINYL CHLORIDE, 51 - CARC/79/05160 SO - Toxicol Lett; 3(6):337-362 1979 LA - ENG AQ - The tumorigenicitv and metabolism of vinyl chloride (VC) and vlnylidene fluoride (VF) were compared in Wistar rats. Exposure c of newborn rats to VC (2,000 ppm, 8 hr/day, 5 days/uk) for 6 wk resulted in the formation of ATPase-deficienf hepatocellular foci. Similar exposure to VF produced a few single foci after 10 wk. After 16 wk of exposure to VF, the number of foci was less c than that observed after 9 wk of exposure to VC, and it was about c c1/100 the number found after 10 uk of exposure to VC, The rate of the metabolic conversion of VF in the rat was found To be 2 orders of magnitude lower Than that of VC. The very slow metabolism of VF may explain why this compound is much weaker in c eliciting preneoplasTic hepatic foci in newborn rats than VC. (21 Refs ) V 62 AU - Koicumi A I Dobashi Y ; Tachibana Y AO - Dept. Public Health, Faculty Medicine, Univ, Tokyo, Tokyo, Japan TI - CHROMOSOME CHANGES INDUCED BY INDUSTRIAL CHEMICALS. SI - CARC/79/09793 SO Jpn J Ind Health; 21(1):3-10 1979 LA ENG AG Radiat i on-induced chromosome damage has been widely recognised and intensively studied. Recently, attention has focused on chromosome changes induced hy various industrial chemicals. In The case of occupational exposure to loniainq radiation, chromosome breaks are one of The most sensitive biological effects. Chromosome breaks have also been reported in workers exposed To benrene> vinyl chloride monomer, or styrene. Icniging radiation, bencene, and vinyl chloride monomer are known carcinogens, and attention is now being qiven to carcinogenicity of clastog-ens or chromosome-break I ng agents. Studies on in vl tro chromosome breakage induced by benggne and its metabolites, as well as by cadmium, lead, and chromium compounds, are reviewed. The i nil i b i T 1 on of repair of rad i a f i on-I nduced chromosome breaks by clastogens and the significance of cytogenetic studies in industrial medicine are also discussed. (90 Refs) e c 3] fio C/3 03 10 O -4 L i C 00005707 VINYL CHLORIDE PAGE 139 ( 263 AU - Uaxueiler RJ AD - Univ. North Carolina, Chapel Hilli NC 71 - AN EPIDEMIOLOGIC INVESTIGATION OF LUNG CANCER IN A MULTIXENCSIOTIC OCCUPATIONAL ENVIRONMENT. SI - ICDS/79/22703 50 - Diss Abstr Int EBJ ; 39(U):5330 1979 LA - ENG A3 - An excess lung cancer risk (39 observed and 27 expected) was observed among a cohort of A,606 males employed at a synthetic chemical plant since it opened in 1992. Upon review of the pathologic material, the excess was found to be limited to adenocarc:noma and large cell undifferentiated lung cancer. Many of the workers were exposed to vinyl chloride, but other exposures including chlorinated solvents, polyvinyl chloride iPVC ) dust, acrylates, and acrylonitrile existed. Thus, detailed work histories of each cohort member along with exposure ratings of each ]ob for each calendar yr since 19A2 for each of 19 different chemicals (or chemical groups ) were obtained. A serially additive expected dose model was constructed which compared the doses of the chemicals observed for the lung cancer cases to the doses expected based on subccncrts individually matched to the cases. PVC dust appeared to be the most likely etiologic agent. Observed and expected doses were then analyzed by yr before death To uncover The relevant latent period. (Author abstract ) (no Refs) 26A AU " Hultmark D I Sundh K ! Johansson L ; Arrhenius E AD - Dept. Microbiology, Univ, Stockholm, S-106 91 Stockholm, Sweden TI - ETHANOL INHIBITION OF VINYL CHLORIDE METAEOLISM IN ISOLATED RAT HEPATOCYTES. 51 - CARC/79/0A709 SO - Chem Biol Interact; 25(1)11-6 1979 LA - ENG AB - Factors which could influence the metabolism of vinyl chloride (VC) by tlie liver were studied using hepatocytes and liver microsomes from untreated and phenobarb i Tal (PD )-pretreated male strain R Wistar raTs. VC incubated with hepatocytes was metabolized as a linear function of time. The metabolism was unaffected by FB pretreatment cr metyrapone (A0 utl), but was strongly inhibited by ethanol (A nidi and tetrahydrofuran, Dichloro-p-niTroanisole O-dcmefhylase was strongly stimulated in The hepatocyto preparations by F3 pretreatment, and the metabolism of d I chlcr o-p-n l Tr oa.n l s o 1 e was partially inhibited by metyrapone, especially after P3 pretreatment. The liver microsomes showed a hiqh capacity to concert VC to non-volatile products, this capacity being dependent on The presence of a NAD PH-genera t i nq system. The microsomes were e'*en more sensitive than the Intact hepatocytes to ethanol inhibition. (20 Refs) R&S 139108 00005708 VINYL CHLORIDE c PAGE 130 '* fv W- ( 265 All - Tarasova NA ; Kataeva SE c AD - Technological Inst. Neat and Dairy Industry, Moscow, USSR C cTI - DETERMINATION OF VINYL CHLORIDE IN POLYMER MATERIALS, MODEL MEDIA AND FOOD PRODUCTS. SI - CARC/79/04463 SO Gig Sanit; (3 ): 98-50 1979 r cLA - RUS AB - Gas chromatography was used to determine vinyl chloride levels in plastic packages and bottles and in samples of cheese that were packaged in polyvinyl chloride. The use of a vapor-air phase in the chromatographic procedure increased the reliability of the c( assay by 3K-10X. tl Ref) 166 AU AD TI SI SO LA AO Harmsen H Hamburg, W. Germany VINYL CHLORIDE - ALSO A DANGER OF CANCER? IC03/79/21Q02 Forum Staedte Hvgl 30(3):58 1979 GER The considerable progress that has been made in recent yr in the Federal Republic of Germany with respect to the control of vinyl chloride contamination of both the general environment and the immediate environment of the factories where it is processed is summarised, (3 Refs) c ( ( 267 AU AD TI SI SO LA A3 Hall JA No affiliation given VINYL CHLORIDE:'A HAZARD OF THE SEVENTIES. ICD3/79/20710 Oecup Health; 31(5):251-257 1979 ENG How the hazards of vinyl chloride became known in 1979 is described and the experience of one company in dealing with the problem is related. Vinyl chloride compounds have been proven to cause angiosarcoma of the liver and osteolysis of the terminal phalanges of the fingers. The role of the occupational health nurse in dealing with such hazardous industrial coinpounds is stressed. (1 Ref) 268 AU - Kucerova M ; Polivk OV el AD - Pediatric D ept. Pos tgra Epidemioloq y, Pragu C ) Si TI - COMPARATIVE EVALUATION ABERRATIONS AND THE SCE WORKERS OCCUPATION LLY SI - CARC/79/09302 50 - MuTait Res i67(1): 97 -100 LA - EKG A3 - Three blood samples f roi exposed for 10-27 yi- to dose 50-20-!150 ppm) wer< third blood sample iwas , Batora J workers occupationaily ; monomer (VCM-" mean annual l c XI o cn CO CO __L o CD 00005709 VINYL CHLORIDE PAGE 131 Z69 AU AD TI SI SO LA AB exchanges (SCE's). The frequency of chromosome aberrations over a 2-yr period was nonhomogeneous > ranging from O'/.-llX aberrant cells. Chromatid and chromosome breads were detected generally! chromatid and chromosome exchanges cccurred only sporadically. The SCE r frequency was more homogeneous, and it was significantly higher in the cells of VCM workers than in those of controls i ranging from 9.56 to 17.50 SCE`s/cell. Smoking and other habits appeared to have no effect on the frequency of any chromosome changes. It is concluded that the routine and SCE cytogenetic analyses are equally suitable for determining high-dose VCN mutagenicity in vivo. The sensitivities of the two Methods seem to be the same, (19 Refs) Heese B Saverische Akademie fur Arbeits- und Soeiaimedirin Pfarrstrasse 3) 8000 Munich 22, W, Germany CHEMICALLY INDUCED OCCUPATIONAL CANCER, CARC/79/09202 Munch Med Wochenschrt 97(13)1837-833,855 1979 GER Data on industrial chemical carcinocens are reviewed briefly. Arsenic, soot, tar, asbestos, aromatic amines, radiation, benpene , nickel, chromium-containing dust, aichlcrodimethyl ether, chi orodimethy1 ether, and vinyl chloride are the major industrial carcinogens, (no Refs) c c c ( c ( 270 AU - Goldschmidt BM ! Van Duuren BL I Goldstein RC AD - Lab. Organic Chemistry and Careinogenes i s, Inst. Environmental Medicine, New York Univ, Medical Center, New York, NY, 10016 TI - THE REACTION OF GUANINE WITH SOME POTENTIAL METABOLITES OF 1-CHLCRCPROPENE. SI - CARC/79/03939 SO - Tetrahedron Lett! (19 ):1177-1180 1979 LA - ENG AO - The bifunctional alkylating agents 2-chloropropanal and 1-chloro-1,2-epoxypropane , two potential metabolites of 1-chloropropene, were shown to react with guanine in dimethyl sulfoxide to yield the monoalkylatad product 2-chloro-N-propenyl-2N-guanine. 1-Chioroprooenc, the simplest homoloq of vinyl chloride, 13 carcinogenic in animals. (22 Refs) 271 AU - Guenqerich FP I Watanabe PG AO - Dept. Biochemistry, Center Environmental Toxicology, Vanderbilt Univ. Sch. Medicine, Nashville. TN, 37232 TI - NET/.DOLISM OF (190- AND (36C LI - LACE LED VINYL CHLORIDE IN VIVO AND IN VITRO. SI CARC/79/0 3960 SO Biochem PharmacolJ 23(5)1589-596 1979 LA ENG A3 Studies were conducted to establish the roles of liver microsomal cytochrome P-950 and epoxide hydratase In The bioTrans formaticn of vlnvl chloride (VC) To metabolites, particularly those bo_rd to protein and nucleic acids. Label from (190 VC uas covalently 33 (/> to CD O L L C 000057X0 VINYL CHLORIDE PAGE 132 bound to protein and nucleic acids in vivo and in vitro in the presence of Spraque-Dawley rat liver microsomal fractions or highly purified cytochrome P-450 and NADPM-cytochrome P-450 reductase preparotions. The ratio of bound To total nonvolatile metabolites increased in going from the in vivo To the microsomal to the purified system. C36C1VC was metabolized by microsomes and highly purified systems: no label was bound> and most of the metabolized chlorine could be accounted for as chloride ion, Phenobarbital pretreatment of rats did not induce total metabolism of VC in vivo at either The 10-or 250-ppm exposure levels; however, binding to protein and RNA was enhanced at The 10-ppm but not the 250-ppm level. Phenobarbital pretreatment increased The in vitro microsomal conversion of VC to both total and bound metabolites. A sizeable fraction of the label of C14C) VC metabolized in vivo was recovered in the microsomal fraction of the liveri but sodium dodecyl sulfate-polyacrvlamide gel electrophonesis of in vitro incubations indicated that the metabolites were distributed among many microsomal proteins and not localized to cytochrome P-450. Evidence was obtained for The metabolism of the suspected VC metabolite chloroethylene oxide by microsomal epoxide hydratase. However, the epoxide hydratase inhibitor 3,3,3-trichloropropylene oxide, which blocks The microsomal degradation of chloroethylene oxide, did not enhance the level of VC bound to either protein or adenosine. (39 Refs) 272 AU - Magnusson J ; Hallstrom I ; Ramel C AD - Environmental Toxicology Unit, Wallenberg Lab., Univ. Stockholm, S-106 91 Stockholm, Sweden TI - STUDIES ON I1ETA301IC ACTIVATION OF VINYL CHLCRIDE IN DROSOPHILA MELANOGASTER AFTER PRETREATMENT WITH PHEMODARBITAL AND POLYCHLORINATED BIPHENYLS. SI - CARC/79/03961 SO - Cham Biol Interact; 24( 3 ) .'237-293 1979 LA - ENG AB - The metabolic activation of vinyl chloride (VC) by The hepatic m1xed-function oxygenase system was studied in Drosophila melanoqasTer by measuring The uptake of 14C from labeled VC in five different strains with and without pretreatment with phenobarbital or a polychlorinated biphenyl IPCQ: Clcphen A50), The latter compounds are well-known inducers of cytochrome P-450. In accordance with previous data on VC-induced sex-linked recessive lethals , pretreatment with inducers increased the uptake of labeled compound up to 10 times. There was, however, a marked difference in response among the five strains. In particular, The Hikone strain, known to be resistant to insecticides, had a comparatIwely hiqher Initial uptake of VC than any of the other strains tested. However, This uptake was unaffected by phenobarbiTal, even at doses 10 Times higher than those used with the other strains, and it was induced to only a very Small degree by PCO. Crosses between Hikone and an inducible strain indicated essentially a dominance for The Hikone genotype. Tests of inducible strains showed the same response To phenobarbita 1 by 2 hr old larvae and adult males and females. The 00Q05711 VINYL CHLORIDE PAGE 133 use of dimethyl sulfoxide as a solvent decreased both the initial uptake of 14C andi particularly> the induction by PCB. The use of Tween SO as an emulsifier did not hove such an effecT. The interstrain variation in metabolic activation and inducibility has to be considered for optimization of the use of Drosophila in mutagenicity testing. This variation also opens up new possibilities of analyzing the mixed-function oxygenase system biochemically and genetically, (26 Refs) 73 AU - Rannug U ; Beije B AO - Division Toxicology Geneticsi Uallenburg Lab.i Univ. Stockholm* Stockholm, Sweden II - THE MUTAGENIC EFFECT OF 1,2-DICHL0R0ETHANE ON SALMONELLA TYPHIMURIUM. II. ACTIVATION BY THE ISOLATED PERFUSED RAT LIVER. SI - CARC/79/03960 SO - Chein Biol Interact! 24( 3 ): 265-255 1979 LA - ENG A3 - Isolated Uistar rat liver was perfused with a soln containing 1,2-dichloroethane (DCE), 1,2-dibromoethane (DDE), or -chloroethanol (CE), and the mutagenicities of the perfusates for Salmonella typhimur1 urn strains TA1530 and TAI535 Were tested. Bile samples (diluted 10-fold) produced by DCE-treated livers were strongly mutagenic for TA1535, the greatest values (600 and 600 mutants/plate) being observed 15 or 30 min after addition of DCE (360 micromoles (mumol )) at 0 and 90 min, rcspectively. Bile from DBE-treated livers (1 dose of 12 mumol DBE) was also mutagenic for TA1535, producing 50 and 60 mutants/plate at 15 and 30 min, respect l'/ely. Bile from DCE-treated Sprague-Dawley rats was significantly loss mutagenic than that of Wlsfar rat bile (p less than 0.001), and the former was clearly more mutagenic after 30 min than after 15 min. CE Was not mutagenic in this system. The results with DCE and DBE indicated an activation through conjugation to glutathione with a subsequent excretion through the bile. Bile produced bv mice treated ip with DCE (00 mg/kg) was also mutagenic for TA1535, the mutagenicity being greater 30 min after injection than 60 min after injection. S-(2-cnloroethyl )-L-cysteine and N-acety1-5-(2-chloroethy1 )-L-cysteine were equally mutagenic for TA1535 in the concerntratiOn range 0.2-0.6 mumol/plate, whereas S-(2-hydroxyethy1 )-L-cysteine was not directly mutagenic. Differences and similarities in the metabolism of DCE and vinyl chloride are discussed on the basis of these results. (49 Refs) 274 AU AO TI SI SO LA AB - Stellman JM Div, Occupational Health and Toxicology, American Health Foundation, New York, NY THE EFFECTS OF TOXIC AGENTS ON REPRODUCTION. - CARC/79/03335 Occup Health Saf; 43(31 = 36-43 1979 ENG Aspects of the toxicology of human reproduction are reviewed, with particular emphasis on the effects of toxic agents encountered in the workplace. Potential modes of reproductive 1 ^V t, Ay,-;'- j>}<**`S ~'i'* -,i.," c c c c 00005712 VINYL CHLORIDE r PAGE 134 dysfunction include organ dysfunction, genetic defects, gestational effecTs, and postpartum effects. Substances That may affect reproduction include diethylsTlIbestrol (DES), estrogen, thalidomide, anesthetic gases, vinyl chloride, chloroprene, dibromochloropropane, DOT Cl>1,1-trichloro-2,2-bis(p-chlorophenylJethaneJ , copper in intrauterine devices), lead, and nonionizing radiation, (no Refs) 275 AU - Tamburro CH J Creech JL I Greenberg RA I Makk L Whelan JG AD - Cancer Center, Div. Diqestive Diseases and Nutrition, Univ, Louisville, Sch. Medicine, Louisville, KY TI - MEDICAL SURVEILLANCE SYSTEM FOR NEOPLASTIC AND NON-NEOPLASTIC OCCUPATIONAL INJURIES DUE TO INDUSTRIAL CHEMICALS (MEETING ABSTRACT), SI - ICDB/79/17714 SO - Clin Res; 27(2):2B5A 1979 LA - ENG AB - Following the discovery of a rare liver cancer (angiosarcoma) among vinyl chloride polymerization workers in 1974, a prospective medical surveillance program was designed for the earlv subclinlcal detection of occupational injuries, including neoplasia. This prototype program involved the active cooperation of a local hospital, a regional university cancer center, the plant workers, labor leaders, management and regulatory agencies. In the first 4 vr cf operation, this program identified an increased incidence of hepatic angiosarcoma among vinyl chloride workers , as well as an increased occurrence of such non-neoplastic, and possibly ore-malignant, lesions as pelios is hepatis, portal fibrosis, portal hypertension, splenomegaly and mid-zonal pleural fibrous thickening of lung. A systematic mul11-discipi 1 nary evaluation system was developed to determine if the diseases and disorders detected could be related To occupational chemical exposure. This program identified the job-related nature of hepatic angiosarcoma and its causative agent from among 22 different chemicals via individual chemical exposure histories based on a retrospective rank-order system for the various job classifications. This medical health surveillance system can be applied in any industry effectively without significant interference in workers 1 life or industrial function, at a cost effective lewel lav cost less than 5,000 dollars/yr/1000 workers provided that all participating parties actively cooperate, (no Refs) 276 AU - Telles NC ; Thomas LB I Popper H ! Ishak KG I Falk H AD - Bureau Radiological Health, Food and Drug Admin., Rockville, MO, 20357 TI - EVOLUTION OF THOROTPAST-INDUCED HEPATIC ANGIOSARCOMAS. SI - CARC/79/03722 SO - Environ Res! 13(1)174-37 1979 LA - ENG A3 - Pathological findings in 25 cases of Tnorotrast-induced angiosarcoma are presented. CraracteristIc antecedent on precursor changes similar to previously described changes present c c c 33 B? to u CD CO c / L L 00005713 VINYL CHLORIDE (' PAGE 135 277 AU AD TI SI SO LA A3 278 AU AD TI SI SO LA AO in hepatic angiosarcoma secondary To vinyl chloride, or arsenicals or of unknown etiology were found. The antecedent or precursor change consisted of areas with simultaneous activation of both The hepatocytes and sinusoidal cells and associated lesions in the sinusoidal and perisinusoidal spaces. The hepatic cell plates surrounding these areas were compressed, with subsequent development of fibrous septa at the interface between the areas of mixed hyperplasia and the areas of compression. In these multiple areas, multicentric angiosarcomas developed in close approximation to the portal tracts but not To The Thorotrast deposits. (25 Refs) Falk H ) Telles NC ; Ishak KG ; Thomas LB ; Popper H Chronic Diseases Div., Bureau Epidemiology! Center Disease Controli US Dept. Healthi Education and Welfare! Public Health Service! Atlanta, GA, 30333 EPIDEMIOLOGY OF THOROTRAST-INOUCED HEPATIC ANGIOSARCOMA IN THE UNITED STATES. CARC/79/03715 Environ Res; 13(1)165-73 1979 ENG Twenty-six cases of Thorotrast (TT)-induced hepatic angiosarcoma (HAS) were identified in an epidemiologic investigation of HAS's occurring in the US during 1965-1975. TT was administered to the 26 patients (19 men, 7 women) during 1931-1953, with 68/ of the patients being injected in the 1950's. The mean age at the time of exposure was 28.5 vr, and the mean age at death was 55.5 yr, Indications for TT studies were carotid arteriography (15 cases), hopafol i enography (9), femoral arterlography (2), and phlebography (1). Information on The TT dose administered was available for 15 patients, 9 of whom a mean dose of 39.9 ml for carotid angiography, 9 a mean dose of 61.8 ml for hepatolienoqraphy, and 1 a dose of 10-20 ml for a femoral arteriogram. Four patients had a history of preexisting 1iver disease, two had hemolytic anemia, and one had arteriovenous malformat ions. None of the patients had a history of exposure to vinyl chloride, but two had been exposed to arsenic and two to iron dust. An additional two patients were chronic alcoholics. These additional risk factors may have potentiated the effects of TT. (35 Refs ) Woods JS Battelle Human Affairs Res. Centers, 5000 H. E. 51st St., Seattle, WA. 90105 EPIDENI0LC3IC CONSIDERATIONS IN THE DESIGN OF TOXICOLOGIC STUDIES: AN APPROACH TO RISK ASSESSMENT IN HUMANS. CARC/79/03585 Fed Prod 33(5):1891-1896 1979 ENG A six-steo procedure for including eo1de.niolocic conslderat1ons in the design and analysis of laboratory studies designed To estimate risk of toxicity in humans during iow-levei exposure to environmental chemicals Is described. Ep1dem1oiogic data are R&S 139114 c ( c k. L 00005714 VINYL CHLORIDE PAGE 136 first used to identify the incidence of toxicity associated with high-level exposure of humans to a particular agent. This information is used to design chronic toxicity studies in animals that establish a dose-response relationship for that substance. Clinical> epidemiologict and laboratory research data are then Used to adjust for differences in major biological determinants of responsiveness between test animals and human3, and bios tatistical procedures are used to describe the nature of the dose-response rela t i cnsii i p in the low-dose region where community exposure occurs. Human incidence of Toxicity under prevailing environmental conditions is Then esTimaTed from The adjusted animal model. Finally, epidemiologic studies are conducted to confirm (or deny) the validity of the predictive model. Vinyl chloride (VC)-induced hepatic angiosarcoma is used show to how epidemiologic data might be useful in The experimental assessment of Toxicity risk in human populations. Despite numerous uncertainties and assumptions inherent in the procedure, The VC exa'Mpie suggests the importance of a combined epidemiolcqic-toxicologlc approach to risk assessment in humans and to setting exposure limitations for toxic agents in the environment. (30 Refs) c c c v 30 fio CO CO ID 279 AU - Ottenualder H ; Laib Rj ; Bolt HM AO - Institut fur Toxikologie, Universltat Tubingen, WilhelmsTrasse 56, D-7400 Tubingen-1, It. Germany TI - ALKYLATION OF RNA BY VINYL BROMIDE METABOLITES IN VITRO AND IN VIVO. SI - ICD3/79/16345 SO - Arch Toxicol (Berl); 41(4 ):279-286 1979 LA - ENG A3 - The compound tl ,2-140 vinyl bromide was incubated with rat liver microsomes, NADFH, and poivadenvllc acid, poivcyTidvlic acid, or RNA, respectively. Part of The adenosine moieties in RNA or in polyadonylic acid were alkylated and labeled 1,N(6)-ethenoadenosine structures were formed. Part of the cytidine moieties were converted into 3>N(4)-ethenocytidine, In addition, a further unidentified cytidine alkylation product was observed which was not seen in experiments using (1,2-140 vinyl chloride, t.'hen rats were exposed to (1,2-140 vinyl bromide, radioactive ethenoadenosine and ethenocytidine were present in hydrolysates of liver RNA. A further alkvlation product was observed in the RNA hydrolysates which did not occur in experiments using (140 vinyl chloride. The data show that vinyl brcmide metabolites alkylate nucleic acids! although in general in this respect vinyl bromide and vinyl chloride behave similarly, some differences are observed in the alkylation behavior of both compounds. (Author abstract) (14 Refs) U1 c c c c ^'xj;l-w.r-"'.;'V r > *->-1'';,. TM- -1 <i c J '4 OOOOS715 VINYL CHLORIDE ( PAGE 137 60 AU - Bartsch H ; Malaveilie C ; Barb in A > Planehe G c AD ~ International Agency for Res. Cancer> 150 Cours Albert-Thomas, c F-69372 Lvoni Cedex 2, France TI - MUTAGENIC AND ALKYLATING METAEOLITES OF HALO-ETHYLENES, c CHLOROBUTADIENES AND DICHL0R03UTENES PRODUCED BY RODENT OR HUMAN LIVER TISSUES. EVIDENCE FOR OXIRANE FORMATION BY P450-LINKED ( MICROSOMAL MONO-OXYGENASES, SI - CARC/79/03420 SO - Arch Toxicol (Bari); 41(4 ):99-277 1979 c LA - ENG AB - The abilities of various haloolefins to induce his+ revertants in Salmonella typhimurium strains TA100 and TA1530 in the presence of mouse or human postmitochondrlal liver supernatants were c studied. With mouse liver microsomes> mutagenicity decreased in the following order: 3i4-dichlorobutene-1 greater than l. 1-chlorobutadiene greater than 2-chlorobutadiene greater than 30 vinyl bromide greater than vinylidine chloride (VQC) greater thoi vinyl chloride (VC), 1,1,2-Trichloroethylena and 1i1-diflucroethylene were marginally mutagenici and CO tetrachloroethylene and vinyl acetate were ncnmutaqenic. With human liver fractions, VC, vlnvl bromide, VDC, and 2-chlorobutadiene were mutagenic. 1,4-DIchloro-2,3-epoxybutane to to was less mutagenic than 1,4-dlchlorobutene-2, the mutagenicity of which was increased by liver microsomes. The mutagenicities of VC O and VDC were increased up to twofold in the presence of liver microsomes from rats pretreated with phenobarbital or 3-methylcholanthrene but preqnenolone-16alpha-carbonitrile, aminoace tonitrile , disulfiram pretreatment decreased the mutagenic effects. VC and, probably, vinyl bromide were C epoxidiged by mouse liver microsomes. 2-Chlorobutadiene, but not 1,1-di f luorce thy lena , 1,1-d i chi oroe thyl ene , or' 1,1 > 2-tr i chlor-oe thylene , yielded an alkylating intermediate. The alkylating activity of 2-chlor'o- and 1-chlorobutadi ene, 3,4-di chlorobutene-1 , and 1,4-d i chlcr'obu t ene-2 and its 2,3-epoxlde derivative was not related quantitatively to mutagenicity. The data indicate that oxidation of the double bond in certain haloolefins is a common pathwav in the formation of biologically active intermediates. (73 Refs) \ 281 AU B-ahlman LJ ! Alexander V ; Infante PF ! Wagoner JK ! Lane JM AU Dinqhnrn E AD Natl. Inst. Occuoational Safety and Health, 5600 Fishers Lane, Rockville, MD, 20557 (,, TI VINYL HALIDES: CARCINOGENICITY. VINYL BROMIDE, VINYL CHLORIDE, AND VINYLIDINE CHLORIDE. SI CARC/79/03415 SO Am Ind Hyq Assoc j; 40(4!:A-30-A-40 1979 LA ENG A3 Laboratory studies demonstratinq the carcinogenicity and mutaqenicity of vinyl chloride (VC), vinylidine chloride (VDC), and vinyl bromide (VB) are reviewed, together with studies demonsTrating the carcinogenicity and mutagenicity of VC in  i'A-, c 00005716 c VINYL CHLORIDE PAGE 133 humans. Liver angiosarcomas have been induced in raTs or mice by vinyl halide concentrations of 25-55 ppm. IT is recommended that c V3 and VDC be considered in the workplace as potential carcinogens to humans and controlled with The same degree of prudence as VC. (35 Refs) c 232 AU - Diubankova EN ! Bykhovskii AV AD - F. F. Erisman Res. Inst. Hygiene. Moscow, USSR TI - HAZARDS ASSOCIATED WITH EXPOSURE TO VINYL CHLORIDE ANO POLYVINYL CHLORIDE MATERIALS. SI - CARC/79/03209 SO -Gig Sanit! (l):69-79 1979 LA - RUS AB - Current data on the hazards of vinyl chloride (VC), in general, and of the use of polyvinyl chloride packages, in particular, are ( reviewed. Seventeen cases of liver angiosarcoma have been reoorted in workers in the VC industry (compared with the total 95 cases reported in the world literature). In addition to liver angiosarcomas , The workers had an increased incidence of cancer (.. of the respiratory, CNS, lymph, and hematopoietic systems. The long-term storage of alcohol in PVC bottles showed distinct organoleptic changes in the alcohol that prompted a ban on the use of PVC containers for food products containing alcohol, (26 Refs ) 283 AU - Buffler PA ; Wood S ! Eifler C ! Suarez L I Kilian DJ AD - Unlv, Texas 5ch, Public Health, P. 0. Box 20106, Houston, TX, 77025 TI - MORTALITY EXPERIENCE OF WORKERS IN A VINYL CHLORIDE MONOMER PRODUCTION PLANT. SI - CARC/79/03199 SO - J Occup Med; 21(3):195-203 1979 LA - ENG AB - A mortality follow-up study was conducted of 969 white men emoloycd in a vinyl chloride monomer (VCM) production plant for at least two consecutive mo between 1998 and 1975. Eight of The 23 deaths in this group were due to malignant neoplasms, 9 from lung cancer. No angiosarcomas or other liver tumors Were observed. The eight persons who died of cancer were initially exposed to VCM prior to 1963, and the four with lung cancer, prior to 1958. Six of the 28 deaths, including 2/3 cancer deaths, occurred among a subgroup of 165 workers exposed to 1,9-dioxane. The total number of observed cancer deaths was not significantly different Than That expected, but a significant excess was noted for maliqnant neoplasms of The respiratory system. The effects of smoking, duration of exposure to VCM, and level of exposure and the combined effect of duration and level of exposure were analyzed separaTely. A 5 yr latency requirement was maintained for all analyses except for the smoking analysis. Using a minimum latency period of 5 yr from the date of Initial exposure to VCM, the excess of respiratory cancer was moderate but not significant for the 319 employees satisfying This criterion. Both a longer duration and a higher level of exposure during the first 5 yr v R&S 139117 u c 00005717 VINYL CHLORIDE ( PAGE 139 R8iS 139118 cr were associated with a significant excess of respiratory career. However when duration and level of exposure were combined, the c results were not significant. In spite of the discrepancy in the results of dose-response analyses, the results suggest that a relationship exists between exposure to VCM and respiratory cancer. (7 Refs) c 284 AU - Fortwengler HP ; Jonas D I Tamburro CH t Espinosa E AD - Univ. Louisville Sch. Medicine, Louisvillei KY, 40232 TI - FACTOR VIII CONTENT AS EVIDENCE FOR ENDOTHELIAL ORIGIN OF VINYL CHLORIDE ASSOCIATED LIVER ANGIOSARCOMA (MEETING ABSTRACT). SI - ICDB/79/14 739 SO - Fed Proc! 3S(3,part2)(999 1979 LA - ENG AB - To ascertain the endothelial cell origin of VCA we have looked for Factor VIII in the tumor since this factor appears to be specific for such cells. Frozen sections of three VCA and one idiopathic case were examined for presence of Factor VIII by indirect Immunofluorescence. Sections of angiosarcoma demonstrated a strikingly increased specific fluorescence which lined enlarged sinusoids. This intense fluorescence was easily seen on a low power (ICOx) as an irregular or splotchy pattern. Occasional striations of linear fluorescence which did not follow hepatic cords ware also present. A similar pattern of staining was also given by the idiopathic angiosarcoma but was never seen in sinusoids of normal liver. These observations were further supported by the finding that absorption of Factor VIII antiserum with experimental angiosarcoma tissue resulted in complete inhibit ion of immunofluorescence. These findings demonstrate that VCA and idiopathic angiosarcoma include proliferating cells containing Factor VIII and therefore strongly support an endothelial cell origin of this tumor. (1 Ref) t 285 AU - Goldschmidt BM ; Van Duuren BL ! Goldstein PC ; Smith AC AD - Lab, Organic Chemistry, Inst. Environmental Medicine, New York Univ, Medical Center, New York, NY, 10016 TI - CARCINOGENICITY AND CHEMICAL REACTION WITH GUANINE OF 1-CHLOROPROPENE AND TWO OF ITS POTENTIAL METABOLITES (MEETING ABSTRACT). SI ICOB/79/13057 SO Proc Am Assoc Cancer Res I 0)90 1979 LA ENG AB 1-Chloropropene, the simplest homologue of the human carcinogen vinyl chloride, alonq with two of its potential metabolites, 1-chloro-l,2-epoxypropane and 2-chloropropanal, were tested for carcinogenicity in female ICR/Ha Swiss mice (30/group). Peoeated skin application of the alkane or aldehyde, and single dose initiation of the three compounds followed by promotion with phorbol myrisfate acetate failed to yield skin Tumors. However, weekly sc injection of the aldehyde (1.0 mg) yielded 4 local sarcomas (P less than 0.005). Weekly intraqastric feeding of the alkene (1.0 mg) led To 10 foresfomach papillomas and 3 carcinomas (P less Than 0.0005) while The aldehyde (1.0 mg) led To 6 t c c :} r- c c c (; (. ( s Wm 3 f '* ' 00005713 VINYL CHLORIDE PAGE 140 foresTomach papillomas (P less Than 0,05). Upon being allowed to react with guanine in dimethylsulfoxide the alkene failed to c react) while the epoxide and aldehyde yielded The identical new compound) C8H6C1H50. Based on UV and nuclear magnetic resonance spectra and other data The structure of the compound was established. It is an enamine formed by reaction at the 2-amino group of guanine. It should be noted that the potent carcinogenic metabolites of benzo(aJpyrene react predominantly with The 2-amino group of guanine in polynucleotides> just as The potential metabolites of 1-chloropropene did in our study, (no Refs ) c c 286 AU - Lande SS AD - Center Chemical Hazard Assessment, Syracuse Res. Corporation, Merrill Lane, Syracuse, NY, 13210 TI - MEASUREMENT OF ATMOSPHERIC VINYL CHLORIDE. SI - ICDB/79/13784 SO - Am Ind Hyg Assoc JI 40(2):96-107 1979 LA - ENG AB - Vinyl chloride atmospheric assays were reviewed for lowest detection limits and most specific measurements. Vinyl chloride is widely used, especially for polyvinyl chloride production, an is a potent carcinogen known to cause hepatic angiosarcoma. Gas chromatography of a sample adsorbed on charcoal is apparently th most sensitive and reliable method. (41 Refs) c J3 (/) CO to CO 287 AU - Dannaher C ! Yam LT I Tamburro C AD - Div, Hematology-Oncology and Vinyl Chloride Project, Univ, Louisville, Louisville, KY, 40202 TI - VINYL CHLORIDE ASSOCIATED HEPATIC ANGIOSARCOMA CHEMOTHERAPY (MEETING ABSTRACT). SI - ICD8/79/13247 SO - Proc Am Assoc Cancer Res; 20:353 1979 LA - ENG AB - Hepatic angiosarcoma is a rare tumor probably arising from the vascular lining cells. Industrial exposure to vinyl chloride used in plastics production has been found to be associated with a 400-fold increase of tumor incidence over that expected in the general populatiodn. By the time of diaqnosls, the tumor is usually diffusely spread throughout the liver and surgery or radiation therapy are not treatment alternatives. Mean duration of survival of untreated patients is 6 mo. We have investigated the use of systemic chemotherapy in a group of workers with hepatic anqiosarcoma from a local industry usinq vinyl chloride. Five patients with histological diagnosis were studied. All of The patients received adriamvcin 60 mg/square meter (m2) iv every 3-4 wk. In four patients this was combined with Cytoxan 600 mg/m2 and methotrexate 20 mq/m2. Mild thrombocytopenI a and/or granulocvtopenia was the rule with each treatment course. CMe patient developed sepsis durinq a period of granulocytopenia. No patient died due to complications of chemotherany, Response Criteria Included significant change In liver size, tumor size, liver function test and performance status lasting at least 2 mo. e c c. L L a C ic 00005719 VINYL CHLORIDE PAGE 141 L cc Three patients had an objective response lasting 4, 9 and 48+ mo. One patient had stable disease for 10 mo. and the fifth patient c chad progressive disease. Responding patients maintained on excellent performance status during therapy. Following evidence of no response or progressive diseasei patients expired in , 3, 4i and 6 mo > respectively. Survival from time of diagnosis was 4i ( Hi 13i 15 and 48+ mo. Sufficient data are not available from these patients to recommend a specific drug or combination for use in hepatic angiosarcoma, but our data indicate that chemotherapy can improve quality and duration of survival, (no Refs ) 33 88 AU Fishbein L CO AD National Center Toxicoloqical Res-. Jefferson, AR> 7079 TI POTENTIAL HALOGENATED INDUSTRIAL CARCINOGENIC AND MUTAGENIC CHEMICALS. I. HALOGENATED UNSATURATED HYDROCARBONS. co co SI CARC/79/0961 SO Sci Total Environ; 11():111-161 1979 LA ENG to o AB Data on the carcinogenicity and mutagenicity of several of the most industrially significant halcgenated unsaturated hydrocarbons are reviewed to assess the nature of their present potential risk. These compounds are vinvl chloride, vinylidlne chloride, trichloroethylene , perchiorcathyleno, chloroprena, trans-1,4-dichlcrobutene, hexacnlorobutadlene, and allyl chloride. Aspects of their synthesis (primarily in terms of the nature of possible hazardous trace impurities), production volumes and use patterns, chemical and biological reactivity and V. stability, environmental occurrence, and national permissible Worker' exposure levels are considered. E.vper i men t al and human epidemiologic evidence of the careinoqemc1ty and mutaqenicity of cC. the hydrocarbons is reviewed, as are data concerning their in vivo and in vitro metabolism. ( 30 Refs) 89 AU AD TI SI SO LA AB Renga G Istituto di Igiene, Dniversita degli Studi di Ancona, Ancona, Italy BRONCHOPULMONARY TUMORS: EPIDEMIOLOGY. 0ARC/79/0786 Minerva Med; 70< 3 ):173-194 1979 ITA Epidemiological and etiological data on iunq cancer are reviewed. In Europe, lung cancer mortality is greater than 100/100,000 in England; 61-99/100,000 in Germany, Switzerland, Austria, Denmark, Netherlands, Belgium, and Finland; 31-60/100,000 In Poland, Bulgaria, Greece, Hungary, Italy, France, Ireland, and Sweden; and 16-30/100,000 in Yugoslavia, Spain, Portugal, Romania, Norway, arid Iceland. In Italy, a positive correlation was found between the size of a city in terms of population and lunq cancer mortality. Air pollution, occupational exposure to harmful substances, and SMiokinq are cons I dered the principal environmenta 1 factors of lung cancer. Industrial pollutants suspected of inducing lung cancer in humans include uranium, e c L L 00005720 VINYL CHLORIDE PAGE 142 radon i hematite, polycyclic aromatic hydrocarbons > asbestos i arsenici chromiumi nickel, mustard gas, acrylonitrile, chloromethyl ether, and, possibly, beryllium and vinyl chloride. Carcinogens detected in tobacco smoke include dime thyInitrosamine , diethyInitrosamlna, methylethylnitrosamine, N-nitrosopyrrolidine, nitrosopiperidine, benzoiaJpyrene, methvlbenzo(aJpyrene , dibenzoacrldlne, dibenzocarbazole, beta-naphthylamine, benzo fluoran thene, me thy1fluoran thene, benzanthracene, chrysene, nitrosoanabasine, benzophenanthrene, nitrosonornicotine, polonium-210, and arsenic. (55 Refs) 290 AU - Chen KT ; Bolles JC ; Gilbert EF AD - Dept. Pathology, Univ. Wisconsin Center for Health Sciences, Madison, WI TI - AGI05ARC0HA OF THE SPLEEN. SI - ICDB/79/10470 SO - Arch Pathol Lab Med; 103(3):122-124 1979 LA - ENG AB - Results of the ultrastructural study of one of two cases of splenic angiosarcoma established the blood vessel origin of this tumor. Fifty-three previously reported cases were reviewed. Hone of the 55 patients had a history of exposure to thorium dioxide, vinyl chloride, or arsenic, 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, and that tumors associated with thorium dioxide, vinyl chloride, or arsenic commonly involve the liver with sparing of the spleen. (Author abstract) (29 Refs) 2 91 All - Zuccato E I Marcucci F i Fanelli R I Muss ini E AO - Istituto di Richerche Farmacologiche 'Mario Negri', Via Eritrea 62, 20157 Milan, Italy TI - HEAD-SPACE GAS-CHROMATOGRAPHIC ANALYSIS OF VINYL CHLORIDE MONOMER IN RAT BL0C0 AND TISSUES. SI - CARC/79/02455 SO - Xenobioticai 9(1):27-31 1979 LA - ENG AB - Vinvl chloride monomer (VCM) levels in rat blood and tissues were measured by a head-space gas chromatograph fitted with a flene ionization detector. Male CD rats were qtven VCM (1, 5, or 10 mg/Kg iv or 10 mg/kg po) and killed 1-120 min later, VCM deposition was determined in blood, liver, kidney, brain, and lung. VCM was distributed rapidly after iv administration I blood had the highest concentration at 1 min, but brain and kidney levels attained equilibrium with blood levels within 2 min of injection. VCM in both blood and tissues was no longer detectable at 15 min for the highest iv dose and at 4 min for the lowest. VCM concentrations were lower in the lung than in blood and other organs at all times. Liver concerntrations were generally lower than those of brain and kidney. VCM reached a high concentration in blood at 5 min after po administration, indicating rapid absorption from the gastrointestinal tract. At 60 min it was 13 CO w to to ro 00Q0S721 VINYL CHLORIDE (' PAGE 143 detectable only in Traces > and aT 120 min it was no longer c detectable. VCM concentrations in The liver were higher than c cThose in blood up To 20 min, but They decreased faster than those in the other tissues, suggesting that metabolism by the liver may determine the disposition of VCM. The technique described is sensitive to 5 nanograms (ng)/ml VCM in blood and 30 ng/g in c Tissues. (IS Refs > 292 AU - Department of Labor c AD - Occupational Safety and Health Admin., Dept. Labor, Washington, DC TI - OCCUPATIONAL SAFETY AND HEALTH STANDARDS: TOXIC AND HAZARDOUS SU35TAMCE5. SI - ICDB/79/09301 c SO - Fed Regist; 44(29,Book2):8575-8333 1979 LA - ENG AB - Occupational safety and health standards for toxic and hazardous substances which are applicable to construction are presented. c The substances discussed include asbestos, coal Tar pitch volatiles, 4-nitrobiphenyl, aipha-naphthylamlne, methyl chlcroethyl ether, 3,3-dichlorobenzidine and its salts, bis-chloromethyl ether, beTa-naphthylamine, benzidine, c 4-aminodi phenyl, ethyleneimlne, bete-propriolactone , 2-acetylaminofluorene, 4-dime thylaminoazobenzene, H-nitrosodimethylamine, vinyl chloride, inorganic arsenic, benzene, coke oven emissions, cotton dust tin cotton gins), 1,2-dibromo-3-chloropropane, and acrvlonitrile. (no Refs) 293 AU AD TI SI. SO LA AB 294 AU AD TI SI SO LA AB Hooper NK J Harris RH I Ames BN I Scnneiderman MA Dept, Biochemistry, Univ. California, Berkeley, CA, 94720 CHEMICAL CARCINOGENS (LETTER TO EDITOR). CARC/79/02197 Science; 203(43311:602-603 1979 ENG Two studies cited in a recent report on chemical carcinogens that support the threshold theory, one concerning vinyl chloride and one concerning chloroform, are criticized. The basic arguments that detoxifying mechanisms are overwhelmed at high dose levels and that high doses of chemicals cause pathological damage to tissues and increase their susceptibility To cancer are countered by other studios showing the opposite results. In addition, a biological model implied in the report--that logarithm of the percent of animals developing a tumor is linearly related to the logarithm of the dose--is l nappropr i ate. (16 Refs) Locker GY ; Dorosnou JM ! Zwellinq LA i Chabner BA Clinical Pharmacoloqy Branch, NCI, Bldg. 10, Room 6N119, 9000 Rockville Pike, Gethesda. MD, 20014 THE CLINICAL FEATURES CF HEPATIC ANGIOSARCOMA: A REPORT OF FOUR CASES AND A REVIEW OF THE ENGLISH LITERATURE. CARC/79/02132 Medicine (Baltimore); 58(l):43-64 1979 ENG The clinical features and treatment of hepatic angiosarcoma are e L L C c 00005722 VINYL CHLORIDE 2D CD CO to -u. ro co ( PAGE 144 discussed based on four case reports and a review of 99 cases c from the English literature. An apparent etiology was identified C' cin 43/103 cases: vinyl chloride in 22, thorotrast in 15, arsenicals in 2, radium in 1, and underlying hemochromatosis in 3. The tumor was most common in middle-aged men. The most common symptoms were abdominal pain, weakness, fatigue, and wt loss, and the most common presenting physical findings were hepatomegaly, ascites, and jaundice. Abnormalities in liver function tests, thrombocytopenia, and elevated prothrombin time were frequent c laboratory findings. Arteriography was a valuable diagnostic tool, as was open biopsy at surgery. However, liver biopsy was accompanied by both morbidity and mortality, especially related to bleeding. Problems encountered during the clinical course c included hepatic failure, intraabdominal and gastrointestinal bleeding, and peripheral destruction of blood elements. The median survival time from the first symptom was 5.5 mo, and only 3/ of the patients lived greater than 2 yr. (144 Refs) c 295 AU - Turns D ; Stevenson J AD - Ho affiliation given TI - HEALTH EDUCATION AND WORK MISTRUST IN A CANCER PREVENTION PROJECT. c SI - ICDB/60/52849 SO - UICC Tech Rep Ser! 31:47-52 1973 f LA - ENG V1^ AB - A random sample of 121 workers at the B F Goodrich 4 Chemical Company in Louisville, Kentucky participated in an opinion survey aimed at assessing the prevalence of negative feelings among workers toward a comprehensive medical survei1lance program instituted for the workers who had been exposed to vinyl chloride. About 21/ of the employees felt that the health questions that they had asked had not been properly answered, 12/ believed that the physicians were out To protect the company, 10/ expressed concern about a breach of c confidentiality, and 30/ felt That the company had done the most (compared with unions, government agencies, etc) to protect the employees from the hazards of vinyl chloride. It was concluded that the program was well accepted by The employees. (5 Refs) c 296 AU - Cicek J AD - No a f f i 1 i a t i on g i ven TI - POTENTIAL SIGNIFICANCE OF SOME ASPECTS OF MODERN VINYL CHLORIDE e TECHNOLOGY ON THE GENESIS OF HEPATIC DISEASE. c SI - ICDB/60/4G251 SO - Llbri Oncol I 7( 3/4):227-232 1978 LA - SCR AB - Studies of the effects of vinyl chloride on the development of hepatic disease are reviewed. Occupational exposure To vinyl chloride may result in anqIosarcoma of the liver, and polyvinyl chloride may contain 5-1,000 ppm of vinyl chloride. (44 Refs) c C c c ';- V=CV '.-r-T--,^'': -J-U 00005723 VINYL CHLORIDE PAGE 145 97 AU - Preussinann R AO - Institut Toxikologie und Chemotherapie Deutsches Kresbsforsehungszentrum, 0-6900 Heidelberg 1, W. Germany TI - TOXICOLOGICAL ASPECTS OF FOOD SAFETY - CARCINOGENICITY AND MUTAGENICITY. SI - IC03/80/46077 SO - Arch Toxicol Suppl \ (l):69-34 197S LA - ENG A8 - Oil*: major problam in The evaluation or potential careinegenic rood additives and contaminants is that of thresholds or, batter, of 'no advarsa-effect-levels'. Arguments in favor of The postulated 'irreversibi1iTy' of carcinogenic effects are based on dose-response studies, single-dose and multi-generation experiments as well as on the concept of somatic mutation as the first steps in carcinogenesis with subsequent transmittance of induced defects during cell reolicatlcn. The problem of extrapolation of results of animal experiments using high doses of low exposure and loui incidences in man is not yet solved satisfactorily. Possible practical consequences include zero-tolerance, acceptable thresholds at loti risk and safety factors. Acceptable intakes never should be considered constants but should be changeable as scon as new facts in regard to the safety evaluation are available. Several systems of short-term tests as screening methods are based on mutagenicity tests and offer many advantages. Their critical evaluation is of utmosT importance. Examples of some relevant problems to be discussed include nitrosamines in food products and their formation from ingested precursors J the migration of >'inyl chloride from polyvinyl chloride food packing material. The occurrence of lou levels of chloroform in drinking uiater. (Author abstract) (60 Refs ) 298 AU AU AD TI SI SO LA AO Lambot te-Vandepaer tl ; Noel G ; Rollmann B ; Nercier H Roberfroid M Lab. Biotoxicology, Catholic Univ. Louvain, Sch, Pharmacy, UCL 73.69, Avenue Emm. Mourner 73, B-1200 Bruxelles, Belgium MODIFYING EFFECTS OF STYRENE Oft THE CATALYTIC PROPERTIES OF SOME NICROSCNAL ENZYMES. ICOB/OO/46071 Arch Toxicol (BerlK (l):2S7-290 1978 ENG The recent concern uith the carcinogenic and/or the mutagenic effects of vinyl chloride has focused attention to the potential hazards of a large variety of monomers used In the manufacture of various plastic materials. The structural relationship between styrene (vinyl benzene) and vinyl chloride, as mil as The frequency of human exposure to styrene, prompted us to carefully investigate some of the effects of styrene cn seme microsomal enzymes, the role of the unlch is essential in activation and deactivation processes of most chemical carcinogens. We have recently demonstrated that pretreatment of rats uith different carcinogens selectively increases the affinity of The activating `h"'; V ` / O c c c V. V., h. c 00005724 VINYL CHLORIDE PAGE 1< 33 CO enzymes towards their own substrates, thereby -favoring the production of the active carcinogenic intermediate. In the present experiment> adult male rats have been treated with various doses of styrene, administered either ip or by inhalation. The activities of some microsomal enzymes, such as aryl hydrocarbon hydroxylase, cytochrome P 450. NADFH: cytochrome c reductase, styrene oxidase hydratase and aldrin oxidase were measured. Some of the treatments have been shown to significantly modify the catalytic properties of the enzymatic systems more or less directly implicated in the metabolic transformations of styrene into its mutagenic intermediate! styrene oxide and of this latter one. into inactive styrene glycol, respectively. (Author abstract) 15 Refs) 299 AU - Harden AN AD - Huntingdon Res. Center. Huntingdon, Cambridgeshire. England TI - IMPACT CN DRUGS, FOOD, AND ENVIRONMENT. SI - CARC/79/07096 SO - Proceedings of the 1st International Congress on Toxicology! Toxicology as a Predictive Science, held in Toronto. Canada, 30 March- 2 April 1977. Plea GL, Duncan HA, ed. Mew York, Academic Press, Inc., 670 pp.. 1973, LA - ENG AB - Modifications based on toxicological research could help diminish hazards such as those associated with smoking, including careinogeniciTy . Cancer associated with inhalation of combustion products containing known carcinogens has decreased in the United Kingdom since 1955. and the hazards of exposure to mesothelioma~inducing asbestos particles could be reduced by reducing cigarette smoking. Tile predictive use of animal experimentation must be linked with postmarketing or postexposure monitoring and surveillance. Among the human envirenmental Carcinogens which have been 'predicted* from animal experimentation are mustard gas, vinvl chloride, stilbestrol, and aflatoxin. Foods constitute the most complex group of substances from the standpoint of predictive toxicology. It is suggested that although toxicity testing might delay and added to the expense of the clearance of new medicines, It does not ultimately deprive mankind of valuable therapeutic agents. (85 Refs) 300 AU - Nelson N AD - Inst. Environmental Medicine, New York Univ. Medical Center, New York, NY TI - ENVIRONMENTAL CANCER: INTERPLAY BETWEEN LABORATORY AND FIELD STU0IE5. SI - CARC/79/07093 SO - Proceedings of the 1st International Congress on Toxicology! Toxicology as a Predictive Science, held in Toronto, Canada. 30 March- 2 April 1977. Plaa GL, Duncan HA, ed. New York, Acacemic Press, Inc. , 670 pp., 1978. LA - ENG AB - The respective roles of eoidemiologic and laboratory studies in identifying specific factors leading to a particular cancer are 03 to mro c c c t c c c c L c c h*V7 - ; /U'd/j-lsw-'l' i, ( (. 00005725 VINYL CHLORIDE c PAGE 147 c reviewed. The alkaline chromates have been identified as the agents of probable greatest importance in cancer induction by chromium. Extensive epidemiologic studios on the consequences of childhood scalp irradiation of children for control of ring worm ware augmented by laboratory studies that identified the dose to various biological targets from the procedure. These studies led to the identification of eight thyroid adenomas in 1,500 exposed children at the very low dose of 6 rads to the thyroid. Cigarette smoking has been linked to lung cancer in many studies, but The specific carcinogenic factors have not yet been identified precisely. Cigarette smoke contains promoting and cocarcinogenic agents that subsTantially enhance the activity of The carcinogenic polynuclear hydrocarbons. and The combination of all these factors may produce The carcinogenic effects of cigarette smoke. Vinyl chloride and bis(chloromethy1 )eTher were identified as carcinogens in the laboratory in the absence of epidemiologic evidence. Subsequently, definiTive epidemiologic studies confirmed that occupational cancers had resulted from exposure to These chemicals. A clear association uas established between lung cancer and occupational exposure To the chloroethers. Dimethyl carbamoyl chloride has also been identified as carcinogenic in related studies. (22 Refs) C C c c c ( # ' END 0 F OFFLINE PRINT 30 S O) w to _L to <7> L L v.'