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The lowest observed dose producing a carcinogenic effect (ASL) in rats was1.3 mg/kg body weight per day. [WHO; Environmental Health Criteria 215:Vinyl Chloride p. 145 (1999)]**PEER REVIEWED**Vinyl chloride causes a wide spectrum of tumors in animals and thisspectrum is similar in a number of different species. ... In rats, thefollowing tumors have been described after vinyl chloride inhalationexposure: liver and other angiosarcomas, other liver tumors, mammary glandcarcinoma, nephroblastoma, neuroblastoma, stomach tumors and Zymbal glandtumors. The lowest dose at which an increase in tumor incidences wasobserved when rats were exposed by inhalation was 130 mg/cu m for liverangiosarcoma (ASL) and 13 mg/cu m for mammary tumors. There is evidencethat animals are more susceptible to tumor induction early in life. Thereis also evidence that liver tumors are induced in female rats at lowerdoses than in males. [WHO; Environmental Health Criteria 215: VinylChloride p. 145 (1999)]**PEER REVIEWED**The effect of age on the susceptibility to induction of ASL in SpragueDawley rats was studied ... .Rats aged 6, 18, 32 or 52 weeks were exposedto vinyl chloride at the same dose level and exposure period. ... Theresults in this demonstrated that the older the rats were at the start ofthe exposure period, the greater was the tumor incidence. The maximumincidence was observed in male rats 52 weeks old at first exposure and infemales 32 weeks old at first exposure (significantly increased comparedto 6- or 18-week old females). For males the effect of age wasstatistically significant. [WHO; Environmental Health Criteria 215: VinylChloride p. 167 (1999)]**PEER REVIEWED**Vinyl chloride, a hepatocarcinogen in humans & rodents, can formpromutagenic etheno bases in DNA after metabolic activation. The formationof 1,N6-ethenoadenine (epsilon A) & 3,N4-ethenocytosine (epsilon C)was measured in adult Sprague Dawley rats by immunoaffinity purification& (32)P-postlabelling. A highly variable background was found in alltissues from untreated animals: the mean molar ratios of epsilon A:A &epsilon C:C in DNA ranged from 0.043 x 10(-8) to 31.2 x 10(-8) & from0.062 x 10(-8) to 20.4 x 10(-8), respectively. After exposure to 500 ppmvinyl chloride by inhalation (4 hr/day, 5 days/wk for 8 wk), increasedlevels of epsilon A were found in the liver, lung, circulating lymphocytes& testis, the mean (+/- SD) of induced levels (treated-control values)being (4.1 +/- 1.5) x 10(-8) for these tissues. No incr in the epsilon A:Aratio was observed in kidney, brain or spleen. The levels of epsilon Cincreased in all the tissues examined except the brain. The mean value ofthe induced epsilon C:C ratios was (7.8 +/- 1.2) x 10(-8) for the liver,kidney, lymphocytes & spleen, & these ratios were higher in thelung (28 x 10(-8)) & testis (19 x 10(-8)). The results suggest avariable repair capacity for epsilon A or epsilon C in different tissues.The results are discussed in relation to published studies on theaccumulation & persistence of etheno bases in the liver during &after exposure to vinyl chloride & on mutation spectra in the ras& p53 genes in liver tumours induced by vinyl chloride. In addn,/studies/ show that the linear relationship established for monofunctionalalkylating agents between their carcinogenic potency in rodents &their covalent binding index for promutagenic bases in hepatic DNA holdsfor vinyl chloride. It is concluded that etheno bases are critical lesionsin hepatocarcinogenesis induced by vinyl chloride. ... Further work isneeded on the role of DNA repair pathways & of endogenous lipidperoxidation products in the formation & persistence of etheno bases
in vivo. [Barbin A; IARC 150: 303-13 (1999)]**PEER REVIEWED**Ethenobases are exocyclic adducts formed with DNA by some environmentalcarcinogens such as vinyl chloride or urethane. ... Increased levels ofDNA etheno adducts have been measured in target tissues from rodentsexposed to vinyl chloride or urethane. Hepatic tumours caused by exposureto vinyl chloride in humans & in rats & lung tumours induced byurethane in mice exhibit base pair substitution mutations in the ras &p53 genes which seem to be exposure-specific & consistent with thepromutagenic properties of ethenobases. Background levels of ethenoadducts have been detected in DNA from non-exposed humans or animals,pointing to an alternative, endogenous pathway of formation. Thisbackground may be affected by dietary factors. It could arise from thereaction of trans-4-hydroxy-2-nonenal (or its epoxide2,3-epoxy-4-hydroxynonanal), a lipid peroxidation product, with nucleicacid bases. Elevated levels of etheno adducts are found in hepatic DNAfrom humans & rodents with genetic predisposition to oxidative stressand lipid peroxidation in the liver, & with an associated increasedrisk of liver cancer. These data suggest that DNA ethenobases could serveas new biomarkers of oxidative stress/lipid peroxidation. [Barbin A; ActaBiochim Pol 45 (1): 145-161 (1998)]**PEER REVIEWED**Previous studies have shown that a high proportion (5/6) of human liverangiosarcomas (ASL) associated with exposure to vinyl chloride (VC)contains a GC-- > AT mutation at the Ki-ras codon 13. This mutation,however, has not been found in 5 ASL or 2 hepatocellular carcinomas (HCC)induced in rats by VC. These 2 HCC did contain a mutation at codon 61 ofthe Ha-ras gene. In order to extend this study & further explore themechanisms of tumour induction, an addl 6 ASL & 6 HCC induced in ratsby VC were analysed for ras gene point mutations, as well as 10 rat &10 murine ASL induced by vinyl fluoride (VF), & 5 ASL, 6 Kupffer cellsarcomas, 4 HCC & 2 cholangiocellular carcinomas induced by Thorotrastin rats. Tumour DNA was analysed by PCR-SSCP & direct sequencing. Noneof the rodent ASL contained a mutation at codon 13 of the Ki-ras geneshowing that the ras gene mutational pattern is species-specific. TheCAA-- > CTA mutation, previously found at codon 61 of the Ha-ras gene inrat HCC, was observed in 5 further VC-induced HCC but was not detected inthe Thorotrast-induced HCC, suggesting carcinogen-specificity. Thismutation was also absent in VC-induced ASL, which supports thecell-specificity of the ras mutational pattern in chemically inducedtumours. No predominant mutation was detected in VF- &Thorotrast-induced tumours. Thus, a given mutation in a tumour may becarcinogen-specific but also depend on the species & the cell type.[Boivin-Angele S et al; Int J Cancer 85 (2): 223-227 (2000)]**PEERREVIEWED**Vinyl chloride is a known human & animal carcinogen that inducesangiosarcomas of the liver. /The authors/ review here studies on theformation & repair of DNA adducts associated with vinyl chloride &vinyl fluoride in exposed & control rodents & unexposed humans.These vinyl halides induce etheno (epsilon) adducts that are identical tothose formed after lipid peroxidation. Of these adducts,N2,3-ethenoguanine (epsilon G) is present in greatest amounts in tissuesof exposed animals. After exposure to vinyl chloride for four weeks,epsilon G levels attain steady-state concns, such that the amount of newlyformed adducts equals the number of adducts that are lost each day. Wereport the first dosimetry of epsilon G in rats exposed to 0, 10, 100 or
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: exposure groups did not differ from
Page 35 and 36: developed to localize the promutage
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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