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1100 ppm vinyl chloride for 5 days or 4 wk. The number of adductsincreased in a supralinear manner. Exposure to 10 ppm vinyl chloride for 5days caused a 2- to 3-fold incr in epsilon G over that of the controls,while 4 wk exposure resulted in a 5-fold incr. This was confirmed with[13C2]vinyl chloride & by measuring exogenous & endogenous adductsin the same animals. Exposure to 100 ppm vinyl chloride for 4 wk caused a25-fold incr in epsilon G levels over that found in control rats, whileexposure to 1100 ppm resulted in a 42-fold incr. The amount of endogenousepsilon G was similar in liver DNA from rats & humans. A comparableresponse to exposure was seen in rats & mice exposed to 0, 25, 250 or2500 ppm vinyl fluoride for 12 months. There was a very high correlationbetween epsilon G levels in rat & mouse liver at 12 months & theincidence of haemangiosarcoma at 2 yr. /The authors/ were able todemonstrate that the target cell population for angiosarcoma, thenonparenchymal cells, contained more epsilon G than hepatocytes, eventhough nonparenchymal cells are exposed by diffusion of vinyl halidemetabolites formed in hepatocytes. The expression of N-methylpurine-DNAglycosylase mRNA was induced in rat liver after exposure to either 25 or2500 ppm vinyl fluoride. When this induction was investigated inhepatocytes & nonparenchymal cells, it was found that the latter hadonly 20% of the N-methylpurine-DNA glycosylase mRNA of hepatocytes, &that only the hepatocytes had induction of this expression after exposureto vinyl fluoride. Thus, the target cells for vinyl halide carcinogenesishave much lower expression of this DNA repair enzyme, which has beenassociated with etheno adduct repair.[Swenberg JA et al; IARC Sci Publ150: 29-43 (1999)]**PEER REVIEWED**Dose-response relationships of genotoxic agents differ greatly dependingon the agent & the endpoint being evaluated. Simple conclusions thatgenotoxic effects are linear cannot be applied universally. The shape ofthe molecular dose of DNA adducts varies from linear, to supralinear, tosublinear depending on metabolic activation & detoxication, &repair of individual types of DNA adducts. For mutagenesis and othergenotoxicity endpoints, the dose-response reflects the molecular dose ofeach type of DNA adduct, cell proliferation, as well as endogenous factorsthat lead to mutagenesis such as the formation & repair of endogenousDNA adducts. These same factors are important when interpreting the shapeof dose-response data for carcinogenesis of genotoxic agents, however,tumor background variability adds additional complexity. Endogenouslyformed DNA adducts may be identical to those formed by chemicals, as inthe case of vinyl chloride & ethylene oxide, or they may be thoseassociated with oxidative stress. Data presented in this paper demonstratethat the exogenous number of adducts induced by 5 days of exposure to 10ppm vinyl chloride is only 2.2-fold > that present as a steady-stateamount in unexposed control rats. Similar data are shown for ethyleneoxide. Extremely sensitive methods have been developed for measuring themolecular dose of genotoxins. These methods can detect DNA adducts as lowas 1 per 10(9) to 10(10). However, in view of the high number ofendogenous DNA adducts that are present in all cells, it is unlikely thatcausal relationships can be attributed to very low numbers of such DNAadducts. Effects of both exogenous & endogenous DNA adducts need to befactored into the interpretation of chemical exposures. [SWENBERG JA etal; MUTATION RESEARCH 464 (1): 77-86 (2000)]**PEER REVIEWED**Etheno adducts in DNA bases are formed from exogenous agents such as vinylchloride & urethane, but also via endogenous lipid peroxidationproducts like trans-4-hydroxy-2-nonenal. An immunohistochemical method was
developed to localize the promutagenic 1,N(6)-ethenodeoxyadenosine DNAadduct in liver of rats exposed to vinyl chloride or an iron overload withor without carbon tetrachloride. Six monoclonal antibodies, previouslyproduced through collaborative efforts, were screened for their optimaladduct recognition & low background formation. The antibody generatedby clone EM-A-4 was found to be most suitable. Semi-quantitative imageanalysis of relative pixel intensity showed approximately 1.5 times higheradduct levels (P < 0.05) in the livers of rats treated with vinylchloride or an iron overload when compared with untreated controls.Significantly elevated adduct levels persisted in vinyl chloride-treatedrat liver 14 days after cessation of exposure, suggesting that this adductis not rapidly eliminated from rat liver DNA. Using the newimmunohistochemical method it is possible to visualize this promutagenicetheno-DNA adduct that may play a role in oxidative stress & lipidperoxidation-induced DNA damage in carcinogenesis. [Yang Y et al;Carcinogenesis 21 (4): 777-781 (2000)]**PEER REVIEWED**TSCA TEST SUBMISSIONS:The ability of vinyl chloride (VC) to induce morphological transformationin the BALB/3T3 mouse cell line (Cell Transformation Assay) was evaluated.Based on preliminary toxicity determinations (exposure time=1 day), VC wastested as a gas in an exposure chamber which contained VC in the medium atconcentrations of 0, 4, 20, 100 and 250 ug/ml in the medium (correspondingto a measured concentration in the chamber of 0, 4.1 and 9.0, 69, 506 and1024 ppm, respectively) with cell survival ranging from 92% to 47% fortreated cells. VC clearly exhibited a statistically significant increasein transformation activity when compared with controls.[Arthur D. Little,Inc.; Cell Transformation Assays of 11 Chlorinated Hydrocarbon Analogs.(1983), EPA Document No. 40-8324457, Fiche No. OTS0509392 ]**QC REVIEWED**The effects of vinyl chloride were examined in the mouse hepatocyteprimary culture/DNA repair assay. Based on preliminary toxicity tests,vinylchloride was tested at concentrations of 5, 10 and 15% and was foundto becytotoxic at the 15% concentration. Vinyl chloride was genotoxic atallconcentrations tested.[Naylor Dana Institute; DNA Repair Tests of 11Chlorinated Hydrocarbon analogs. (1983), EPA Document No. 40-8324292,Fiche No. OTS0509403 ]**QC REVIEWED**The effects of vinyl chloride were examined in the rat hepatocyte primaryculture/DNA repair assay. Based on preliminary toxicity tests, vinylchloride was tested at concentrations of 5, 10 and 15% as a gas in adesiccator exposure chamber. The highest concentration was too toxic to beevaluated in the assay. The lower two concentrations were nontoxic but didcause a significant increase in the unscheduled DNA synthesis overuntreated controls.[Naylor Dana Institute; DNA Repair Tests of 11Chlorinated Hydrocarbon Analogs. (1983), EPA Document No. 40-8324292,Fiche No. OTS0509403 ]**QC REVIEWED**Chronic toxicity and oncogenicity were evaluated in groups of male andfemale Wistar rats (100/sex/group, except highest dose level,50/sex/group) ingesting vinyl chloride (VC) in the diet at 0, 0.014, 0.13and 1.3 mg VC/kg body weight/day, which was available for 4 hrs/day overthe lifespan of the animals. There was a significant increase in theincidence of liver nodules suspected of being tumors in both sexes,especially in females, at the highest dose level. An increased incidenceof foci of cellular alteration, neoplastic nodules, hepatocellularcarcinomas, liver-cell polymorphism and cysts were observed at the highest
Page 1: The following information was gener
Page 5 and 6: ... ANOREXIA, ... ALLERGIC DERMATIT
Page 7 and 8: cancer. Many of the workers had bee
Page 9 and 10: personnel records of nine chemical
Page 11 and 12: worker consumed more than a very lo
Page 13 and 14: (1): 37-45 (1991)]**PEER REVIEWED**
Page 15 and 16: workers to the vinyl chloride monom
Page 17 and 18: skin cancer could bear some relatio
Page 19 and 20: N-5'-alkylpurine (AP) endonucleases
Page 21 and 22: Agency for Research on Cancer, 1979
Page 23 and 24: LIFE SUPPORT:oThis overview assumes
Page 25 and 26: exposure circumstance entails expos
Page 27 and 28: for carcinogenicity in human epidem
Page 29 and 30: Risk of Chemicals to Man. Geneva: W
Page 31 and 32: exposure groups did not differ from
Page 33: in vivo. [Barbin A; IARC 150: 303-1
Page 37 and 38: WORKERS. THE VALUE OBTAINED WERE IN
Page 39 and 40: (2): 259 (1977)]**PEER REVIEWED**Af
Page 41 and 42: y 1 mg/cu m of either /cmpd/ separa
Page 43 and 44: (1980) as cited in USEPA; Health an
Page 45 and 46: (1975)]**PEER REVIEWED**ENVIRONMENT
Page 47 and 48: The Koc of vinyl chloride is estima
Page 49 and 50: REVIEWED**SEDIMENT/SOIL CONCENTRATI
Page 51 and 52: Fugitive emission sources; (3) Leak
Page 53 and 54: BOILING POINT:-13.3 deg C [Lide, D.
Page 55 and 56: Washington, D.C: U.S. Government Pr
Page 57 and 58: Reactivity: 2. 2= This degree inclu
Page 59 and 60: Vinyl chloride/ decomposes on burni
Page 61 and 62: available./ ... Safety pipettes sho
Page 63 and 64: Analytical procedures ... should be
Page 65 and 66: equipment. [Association of American
Page 67 and 68: done without undue risk. Use water
Page 69 and 70: Fishbein, R. A. Griesemer, A.B. Swa
Page 71 and 72: 673-6121; Production site: Geismar,
Page 73 and 74: 91% FOR POLYVINYL CHLORIDE [Kavaler
Page 75 and 76: halogen-specific detector for the a
Page 77 and 78: phthalate esters, detectable levels
Page 79 and 80: USEPA; Drinking water Criteria Docu
Page 81 and 82: ADMINISTRATIVE INFORMATION:HAZARDOU
Page 83: Field Update on 01/15/1990, 1 field

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