DRAFT - DO NOT CITE OR QUOTE oEPA [NCEA tracking no. for drafts or EPA ID for final] www.epa.gov/iris TOXICOLOGICAL REVIEW OF Vinyl Acetate (CAS No. 108-05-4) In Support of Summary Information on the Integrated Risk Information System (IRIS) DATE [author: insert current date for this draft or Agency completion date (month and year) iffinal] NOTICE This document is an [author: insert Agency Review, Interagency Review or External Review] draft. This information is distributed solely for the purpose of pre-dis semi nation peer review under applicable information quality guidelines. It has not been formally disseminated by EPA. It does not represent and should not be construed to represent any Agency determination or policy. It is being circulated for review of its technical accuracy and science policy implications. U.S. Environmental Protection Agency Washington, DC ------- Reviews ACGIH (American Conference of Governmental Hygienists). (2001) Vinyl acetate. Documentation of the threshold limit values and biological exposure indices 5. ATSDR (Agency for Toxic Substances and Disease Registry). (1986) Minimal risk levels for priority substances and guidance for derivation. Federal Register 61(101):25873-25882. Available online at http://www.epa.gov/fedrgstr/EPA-WASTE/1996/May/Day-23/pr-567.html. ATSDR (Agency for Toxic Substances and Disease Registry). (1992) Toxicological profile for vinyl acetate. U.S. Public Health Service, Agency for Toxic Substances and Disease Registry, Washington, DC. Bascom, R; Bromberg, PA; Costa, D; et al. (1996) Health effects of outdoor air pollution. Am J Respir Crit Care Med 153(1):3—50. BIBRA Information Services. (1991) Toxicity profile of vinyl acetate. Available online at http://www.bibra-information.co.uk/profile-177.html. BAuA (Bundesanstalt fur Arbeitsschutz und Arbeitsmedizin). (2005) Draft risk assessment report for vinyl acetate. Federal Institute for Occupational Safety and Health Division for Chemicals and Biocides Regulation, Dortmund, Germany. Available online at http://ecb.jrc.ec.europa.eu/documents/ExistingChemicals/RISK_ASSESSMENT/DRAFT/R059_ 0807_env_hh.pdf (accessed April 29, 2010). Butterworth, BEB. (1999) A comprehensive approach for integration of toxicity and cancer risk assessments. Regul Toxicol Pharmacol 29(l):23-36. Carthew, P; Griffiths, H; Keech, S; et al. (2002) Safety assessment for hair-spray resins: risk assessment based on rodent inhalation studies. Inhal Toxicol 14(4):401-416. Celanese Corporation. (1976) Vinyl acetate. Submitted to NIOSH by Celanese Corporation, Dallas, TX, Product Standards; 36 pp. Unpublished. Chou C-H SJ; Holler, J; De Rosa, CT; et al. (1998) Minimal risk levels (MRLs) for hazardous substances. J Clean Technol Environ Toxicol Occ Med 7(1): 1-24. Haskell Laboratory for Toxicology and Industrial Medicine. (1967) Report of toxicity of vinyl acetate. Submitted to the American Conference of Governmental Industrial Hygienists by EI du Pont de Nemours and Co., Inc., Wilmington, DE. Unpublished report. Health Canada. (2008) Risk management scope for acetic acid ethenyl ester (vinyl acetate monomer). Environment Canada. Available online at http://www.ec.gc.ca/substances/ese/eng/challenge/batch2/batch2_108-05-4_rms_en.pdf. Henschler, D; ed. (1993) Occupational toxicants. Critical data evaluation for MAK values and classification of carcinogens: volume 5. Weinheim, Germany: Wiley-VCH; 390 pp. Holmberg, B. (1984) The toxicology of monomers of the polyvinyl plastic series. Prog Clin Biol A-l DRAFT - DO NOT CITE OR QUOTE ------- Res 141:99-112. HSDB (Hazardous Substances Database). (2009) Vinyl acetate. National Library of Medicine, Bethesda, MD. Revised 8/20/2009; reviewed 5/7/2009. Available online at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB (accessed April 27, 2010). IARC (International Agency for Research on Cancer). (1979) IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans: vol. 19: some monomers plastics, and synthetic elastomers and acrolein. International Agency for Research on Cancer, Lyon, France 19:341-366. IARC (International Agency for Research on Cancer). (1986) Vinyl acetate. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans: vol 39: some chemicals used in plastics and elastomers. International Agency for Research on Cancer, Lyon, France 39:113— 131. IARC (International Agency for Research on Cancer). (1995) Vinyl acetate. IARC Monographs on the evaluation of carcinogenic risks to humans: vol. 63: dry cleaning, some chlorinated solvents and other industrial chemicals. International Agency for Research on Cancer, Lyon, France. Available online at http://monographs.iarc.fr/ENG/Monographs/vol63/volume63.pdf (accessed April 28, 2010). Maki-Paakkanen, J; Norppa, H. (1988). Nordic Expert Group: vinyl acetate. Arbete och Halsa 33:77-113. Stringer, DA. (1991) Vinyl acetate. German National Library of Science and Technology (TIB), Hannover, Germany. Takeshita, T. (2003) Gene-environmental interactions in alcohol-related health problems: Contributions of molecular biology to behavior modifications. Japanese J Hyg 58(32):254-259. U.S. EPA (Environmental Protection Agency). (1995) Integrated Risk Information System (IRIS) database. Reference concentration (RfC) for vinyl acetate. National Center for Environmental Assessment, Washington, DC. Available online at http://www.epa.gov/iris. Wiltse, J; Dellarco, VL. (1996) U.S. Environmental Protection Agency guidelines for carcinogen risk assessment: past and future. Mutat Res 365(1—3):3—15. 2. CHEMICAL AND PHYSICAL INFORMATION Boxer, PA; Reed, LD. (1983) Health hazard evaluation report no. HET A-82-051-1269. National Starch & Chemical, Meredosia, IL. Prepared for the United States National Institute for Occupational Safety and Health, Cincinnati, OH. Available from the National Technical Information Service, Springfield, VA; PB84-209923. Chemical Week. (2003) Product focus: vinyl acetate monomer, June 25; p. 31. Deese, DE; Joyner, RE. (1969) Vinyl acetate: A study of chronic human exposure. Am Ind Hyg A-2 DRAFT - DO NOT CITE OR QUOTE ------- Assoc J 30:449-457. Frey, HE; Wolfe, AJ. (1977) Vinyl acetate, polyvinyl acetate, and polyvinyl alcohol. SRI International, Menlo Park, CA. Gordon, SJ; Meeks, SA. (1977) A study of gaseous pollutants in the Houston, Texas area. In: Byers, RL; Crocker, BB; Cooper, DW; eds. Dispersion and control of atmospheric emissions: new energy source pollution potential. New York: American Institute of Chemical Engineers; pp. 84-94. Guerin, MR. (1980) Chemical composition of cigarette smoke. In: Gori, GB; Bock, FG; eds. Banbury report: a safe cigarette? Vol. 3. Cold Spring Harbor, NY: CSH Press; pp. 191-204. Kelly, TJ; Ramamurthi, M; Pollack, AJ; et al. (1993) Ambient concentration summaries for Clean Air Act. Title III. Hazardous Air Pollutants. Final report. United States Environmental Protection Agency, Research Triangle Park, NC; USEPA Contract No 68-D80082, EPA/600/R- 94/090. Kollar, V; Kemka, R; Misianik, J; et al. (1988) Determination of vinyl chloride and vinyl acetate in working atmosphere. Chem Pap 42:147-160. Marsden, J; Cuthbertson, AC. (1933) The vapor pressure of vinyl acetate. Can J Res 9:419-423. McNeal, TP; Hollifield, HC. (1993) Determination of volatile chemicals released from microwave-heat-susceptor food packaging. J Assoc Anal Chem Int 76:1268-1275. Pellizzari, ED. (1982) Analysis for organic vapor emissions near industrial and chemical waste disposal sites. Environ Sci Technol 16:781-785. Peralta, R; Infante, R; Cortez, G; et al. (2007) Densities and derived thermodynamic properties of the binary systems of benzene with butyl methacrylate, allyl methacrylate, methacrylic acid, and vinyl acetate at 298.15 K. Chem Eng Com 194:635-647. Petroza, LI; Boikova, ZK. (1975) Determination of small amounts of vinyl acetate in the air, water, alcoholic solutions and food stuffs. Gig Sanit 6:48-49. (Russian) Resa, JM; Iglesias, M; Gonzalez, C; et al. (2001) Excess volumes of binary mixtures of vinyl acetate and aromatic hydrocarbons. J Chem Thermodyn 33:723-732. Samanos, B; Boutry, P; Montarnal, R. (1971) The mechanism of vinyl acetate formation by gas- phase catalytic ethylene acetoxidation. J Catalysis 23(1): 19-30. Santodonato J; Bosch S; Meylan W; et al. (1985) Monograph on human exposure to chemicals in the workplace: vinyl acetate. Syracuse Research Corporation, Syracuse, NY; SRC-TR-85-190. Available online at http://www.ntis.gov/search/product.aspx?ABBR=PB86155157. Simonyi, MI. (1976) Determination of the equilibrium constant of hydrogen bonding between substituted h-[d]-phenols and vinyl acetate in CC14 by i.r. measurements. Spectrochim Acta Part A: Mol Spectrosc 32(7): 1387-1392. A-3 DRAFT - DO NOT CITE OR QUOTE ------- Takehara, Z. (1970) Hydrogenation of some organic compounds in acidic aqueous solutions on noble metal catalysts. Electrochim Acta 15(6):999-1012. Tanii, H; Huang, J; Ohyashiki, T; et al. (1994) Physical-chemical-activity relationship of organic solvents: effects on Na+-K+-ATPase activity and membrane fluidity in mouse synaptosomes. Neurotoxicol and Teratol 16(6):575-582. TRI (Toxic Release Inventory)- (2008) U.S. Environmental Protection Agency, Washington, DC. Available online at http://vvvvvv.epa.gov/TRl/tridata/. Trzeciak, AM; Ziolkowski, JJ. (1987) Homogeneous rhodium complex-catalyzed hydroformylation and related reactions of functionally substituted olefins. J Mol Catal 43(1): 15— 20. Tustin, GC; Colberg, RD; Zoeller, JR. (2000) Synthesis of vinyl acetate monomer from synthesis gas. Catal Today 58:281-291. Valstar, JM; van den Berg, PJ; Oyserman, J. (1975) Comparison between two dimensional fixed bed reactor calculations and measurements. Chem Eng Sci 30(7):723-728. Vasil'yeva, IB; Gelbshtein, AJ; Tolsteekova, IN; et al. (1964) Catalyzed reactions of acetylene in vapor phase: kinetics and mechanism of vapor phase synthesis of vinyl acetate over various metal acetate catalysts. J Catalysis 3(6):574-575. Weast, R. (1974) CRC handbook of chemistry and physics: a ready reference book of chemical and physical data. Cleveland, OH: CRC Press, Inc. Weber, HK; Weber, H; Kazlauskas, RJ. (1999) 'Watching' lipase-catalyzed acylations using 1H NMR: competing hydrolysis of vinyl acetate in dry organic solvents. Tetrahed-Asymmetry 10:2635-2638. West, OR; Bayne, CK; Siegrist RL; et al. (1996) Stability of purgeable VOCs in water samples during pre-analytical holding: part 1: analysis by a commercial laboratory. GRA&I 10:150. Zaidi, SAH. (1988) Catalytic activity of supported liquid-phase lithium—palladium acetate catalysts in the oxidation of ethylene to vinyl acetate. Appl Catal 38(2):353-358. Zhou, X; Zhang, P; Li, Z; et al. (2007) Miscibility behavior of ethylene/vinyl acetate and C5 petroleum resin by FTIR imaging. Anal Sci 23(7):877-880. A-4 DRAFT - DO NOT CITE OR QUOTE ------- 3. TOXICOKINETICS 3.1. ABSORPTION Bogdanffy, MS; Sarangapani, R; Plowchalk, DR; et al. (1999) A biologically based risk assessment for vinyl acetate-induced cancer and noncancer inhalation toxicity. Toxicol Sci 51:19-35. Hazleton Laboratories. (1979) Investigations into the metabolic fate of vinyl acetate in the rat and mouse: Part I. U.S. EPA/OTS public files. Hazleton Laboratories Europe, Ltd., England; document no. FYI-OTS-0184-0278. Kondo, N; Iwao, T; Hirai KI; et al. (1994) Improved oral absorption of enteric coprecipitates of a poorly soluble drug. J Pharm Sci 83:566-570. Plowchalk, DR; Andersen, ME; Bogdanffy, MS. (1997) Physiologically based modeling of vinyl acetate uptake, metabolism, and intracellular pH changes in the rat nasal cavity. Toxicol Appl Pharmacol 142:386-400. 3.2. DISTRIBUTION Blessing, MH. (1974) Storage of vinyl pyrrolidone-vinyl acetate (VP-VA) in rats following endotracheal and subcutaneous injection. Virchows Arch A Path Anat and Histol 362(2): 115- 128. Filov, VA. (1959) On the fate of complex esters of vinyl alcohol and fatty acids in the organism. Gigiena Truda i Professional'nye Zabolevaniya 3(5):42-46. (Russian) Morris, JB; Symanowicz, P; Sarangapani, R. (2002) Regional distribution and kinetics of vinyl acetate hydrolysis in the oral cavity of the rat and mouse. Toxicol Lett 126:31-39. 3.3. METABOLISM Andersen, ME; Sarangapani, R. (1999) Clearance concepts applied to the metabolism of inhaled vapors in tissues lining the nasal cavity. Inhal Toxicol 11(10):873—897. Andersen, ME; Sarangapani, R. (2001) Physiologically based clearance/extraction models for compounds metabolized in the nose: an example with methyl methacrylate. Inhal Toxicol 5:397-414. Bogdanffy, MS; Taylor, ML. (1993) Kinetics of nasal carboxylesterase-mediated metabolism of vinyl acetate. DrugMetab Dispos 21(6): 1107-1 111. Bogdanffy, MS; Randall, HW; Morgan, KT. (1986) Histochemical localization of aldehyde dehydrogenase in the respiratory tract of the Fischer-344 rat. Toxicol Appl Pharmacol 82:560- 567. Bogdanffy, MS; Randall, HW; Morgan, KT. (1987) Biochemical quantitation and histochemical A-1 DRAFT - DO NOT CITE OR QUOTE ------- localization of carboxylesterase in the nasal passages of the Fischer-344 rat and B6C3F1 mouse. Toxicol Appl Pharmacol 88:183-194. Bogdanffy, MS; Sarangapani, R; Kimbell, JS; et al. (1998). Analysis of vinyl acetate metabolism in rat and human nasal tissues by an in vitro gas uptake technique. Toxicol Sci 46(2):235-246. Bogdanffy, MS; Manning, LA; Sarabgapani, R; et al. (1999a) High-affinity nasal extraction of vinyl acetate vapor is carboxylesterase dependent. Inhal Toxicol 11:927-941. Cresswell, DG; Strong, HA; Hopkins, R. (1979) Investigations into the metabolic fate of vinyl acetate in the rat and mouse: part I. Society of the Plastics Industry, Inc., New York; 1910-51/8. Available online at http://www.ntis.gov/search/product.aspx?ABBR=OTS00002780. Genter, M. (2004) Olfactory mucosal metabolic enzymes: modulation of toxic endpoints based on distribution, induction, and age-and species variables. Toxicologist 78:193. Hardman, JG; Limbird, LE; Molinoff, PB; et al.; eds. (1995) Goodman & Gilman's the pharmacological basis of therapeutics. New York: McGraw-Hill Professional; 1825 pp. Hazleton Laboratories. (1979) Investigations into the metabolic fate of vinyl acetate in the rat and mouse: part I. U.S. EPA/OTS public files. Hazleton Laboratories Europe, Ltd.; document no. FYI-OTS-0184-0278. Knowles, S; Jarrett, I; Filsell, O; et al. (1974) Production and utilization of acetate in mammals. Biochem J 142:401-411. Lantz, RC; Orozco, J; Bogdanffy, MS. (2003) Vinyl acetate decreases intracellular pH in rat nasal epithelial cells. Toxicol Sci 75(2):423-432. Morris, JB; Symanowicz, P; Sarangapani, R. (2002) Regional distribution and kinetics of vinyl acetate hydrolysis in the oral cavity of the rat and mouse. Toxicol Lett 126:31-39. Robinson, DA; Bogdanffy, MS; et al. (2002) Histochemical localisation of carboxylesterase activity in rat and mouse oral cavity mucosa. Toxicology 180(3):209-220. Simon, P; Filser, KG; Bolt, HM. (1985) Metabolism and pharmacokinetics of vinyl acetate. Arch Toxicol 57(3): 191-195. Skibsted, U; Hansen, PE. (1990) 1HNMR spin-echo spectroscopy of human erythrocytes. Transformation of exogenous compounds. NMR Biomed 3(6):248-258. Thornton-Manning, JR; Dahl, AR. (1997) Metabolic capacity of nasal tissue interspecies comparisons of xenobiotic-metabolizing enzymes. Mut Res 380(l-2):43-59. Thurman, RG. (1974) Alcohol and aldehyde metabolizing systems. Papers presented at the First International Symposium on Alcohol and Aldehyde Metabolizing Systems in Stockholm, Sweden, July 9-11, 1973. German National Library of Science and Technology (TIB), Hannover, Germany; 611 pp. A-2 DRAFT - DO NOT CITE OR QUOTE ------- Thurner, CA. (1997) Ethanol metabolism in Acetobacter europaeus: purification, characterization and genetic analysis of the membrane-associated alcohol and aldehyde dehydrogenase complexes. Unpublished; 8 pp. German National Library of Science and Technology (TIB), Hannover, Germany. Whitmire, DR. (1992) Rapid ethanol lowering-a bioengineering approach. Crisp Data Base, National Institutes of Health, Georgia. 3.4. ELIMINATION Hinderliter, PM; Thrall, KD; Corley, RA; et al. (2005) Validation of human physiologically based pharmacokinetic model for vinyl acetate against human nasal dosimetry data. Toxicol Sci 85:460-467. 3.5. PHYSIOLOGICALLY BASED TOXICOKINETIC MODELS Andersen, ME; Sarangapani, R. (1999) Clearance concepts applied to the metabolism of inhaled vapors in tissues lining the nasal cavity. Inhal Toxicol 11:873-897. Andersen, ME; Dennison, JE. (2001) Mode of action and tissue dosimetry in current and future risk assessments. Sci Total Environ 274(l-3):3-14. Andersen, ME; Jarabek, AM. (2001) Nasal tissue dosimetry-issues and approaches for "category 1" gases: a report on a meeting held in Research Triangle Park, NC, February 11-12, 1998. Inhal Toxicol 13(5):415-435. Andersen, ME; Sarangapani, R; Frederick CB; et al. (1999) Dosimetric adjustment factors for methyl methacrylate derived from a steady-state analysis of a physiologically based clearance- extraction model. Inhal Toxicol 11:899-926. Andersen, ME; Green, T; Frederick, CB. (2002) Physiologically based pharmacokinetic (PBPK) models for nasal tissue dosimetry of organic esters: assessing the state-of-knowledge and risk assessment applications with methyl methacrylate and vinyl acetate. Reg Toxicol Pharmacol 36(3):234-245. Bogdanffy, MS; Taylor, ML. (1993) Kinetics of nasal carboxylesterase-mediated metabolism of vinyl acetate. Drug Metab Dispos 21:1107-1 111. Bogdanffy, MS; Jarabek, AM. (1995) Understanding mechanisms of inhaled toxicants: Implications for replacing default factors with chemical-specific data. Toxicol Lett 82(83):919- 932. Bogdanffy, MS; Sarangapani, R; Kimbell, JS; et al. (1998) Analysis of vinyl acetate metabolism in rat and human nasal tissues by an in vitro gas uptake technique. Toxicol Sci 46:235-246. Bogdanffy, MS, Manning, LA; Sarangapani, R. (1999a) High-affinity nasal extraction of vinyl acetate vapor is carboxylesterase dependent. Inhal Toxicol 11(10):927—941. Bogdanffy, MS; Sarangapani, R; Plowchalk, DR; et al. (1999b) A biologically based risk A-3 DRAFT - DO NOT CITE OR QUOTE ------- assessment for vinyl acetate-induced cancer and noncancer inhalation toxicity. Toxicol Sci 51(1): 19—35. Bogdanffy, MS; Plowchalk, DR; Sarangapani, R; et al. (2001) Mode-of-action-based dosimeters for interspecies extrapolation of vinyl acetate inhalation risk. Inhal Toxicol 13(5):377-396. Casanova-Schmitz, M; David, RM; Heck, Hd'A. (1984) Oxidation of formaldehyde and acetaldehyde by NAD+-dependent dehydrogenases in rat nasal mucosal homogenates. Biochem Pharmacol 33:1137-1142. The ENVIRON Health Sciences Institute. (2004) Acetaldehyde tissue dosimetry in the upper respiratory tract of rats and humans following acetaldehyde exposure and the potential impact of aldehyde dehydrogenase polymorphisms on nasal tissue acetaldehyde dosimetry. The ENVIRON Health Sciences Institute, Ruston, LA. Goldsmith, DJ; Hilton, PJ. (1992) Relationship between intracellular proton buffering capacity and intracellular pH. Kidney Int 41:43-49. Hinderliter, PM; Thrall, KD; Corley, RA; et al. (2005) Validation of human physiologically based pharmacokinetic model for vinyl acetate against human nasal dosimetry data. Toxicol Sci 85:460-467. ICRP (International Commission of Radiological Protection). (1975) No. 23: report of the task group on reference man. New York, NY: Pergamon Press. ILSI (International Life Sciences Institute). (1994) Physiological parameter values for PBPK models. Risk Science Institute, Washington, DC. Kimbell, JS; Gross, EA; Joyner, DR; et al. (1993) Application of computational fluid dynamics to regional dosimetry of inhaled chemicals in the upper respiratory tract of the rat. Toxicol Appl Pharmacol 121:253-263. Kimbell, JS; Subramaniam, RP. (2001) Use of computational fluid dynamics models for dosimetry of inhaled gases in the nasal passages. Inhal Toxicol 13(5):325—334. Krishnan, K; Johanson, G. (2005) Physiologically-based pharmacokinetic and toxicokinetic models in cancer risk assessment. J Env Sci Health, Part C: Environ Carcinog Ecotoxicol Rev 23(1):31—53. Morris, JB. (1997) Uptake of acetaldehyde vapor and aldehyde dehydrogenase levels in the upper respiratory tracts of the mouse, rat, hamster and guinea pig. Fundam Appl Toxicol 35:91 — 100. Morris, JB; Hassett DN; Blanchard KT. (1993) A physiologically based pharmacokinetic model for nasal uptake and metabolism of nonreactive vapors. Toxicol Appl Pharmacol 123:120-129. Paulsson, B; Bende, M; Ohlin, P. (1985) Nasal mucosal blood flow at rest and during exercise. Acta Otolaryngol 99:140-143. A-4 DRAFT - DO NOT CITE OR QUOTE ------- Plowchalk DR.; Andersen ME; Bogdanffy MS. (1997) Physiologically based modeling of vinyl acetate uptake, metabolism, and intracellular pH changes in the rat nasal cavity. Toxicol Appl Pharmacol 142:386-400. Schwartz, RE, Soelberg, JJ; Corley, RA; et al. (2004) Development of a method for the simultaneous analysis of vinyl acetate and acetaldehyde concentrations in the nasopharyngeal cavity and exhaled breath of human volunteers. Toxicologist 78(l-S):439-440. Stott, WT; Ramsey, JC; McKenna, MJ. (1986) Absorption of chemical vapors by the upper respiratory tract of rats. In: Barrow, CS; ed. Toxicology of the nasal passages [papers from the 7th CUT conference on toxicology]; 1984; Raleigh, NC. Washington, DC: Hemisphere Publishing Corporation; pp. 191-210. Subramaniam, R; Richardson, RB; Morgan KT; et al. (1998) Computational fluid dynamics simulations of inspiratory airflow in the human nose and nasopharynx. Inhal Toxicol 10:91 — 120. Teeguarden, JG; Deisinger, PJ; Poet, TS; et al. (2005) Derivation of a human equivalent concentration for n-butanol using a physiologically based pharmacokinetic model for n-butyl acetate and metabolites n-butanol and n-butyric acid. Toxicol Sci 85:429-446. Teeguarden, JG; Bogdanffy, MS; Covington, TR; et al. (2008) A PBPK model for evaluating the impact of aldehyde dehydrogenase polymorphisms on comparative rat and human nasal tissue acetaldehyde dosimetry. Inhal Toxicol 20:375-390. U.S. EPA (Environmental Protection Agency). (1994b) Methods for derivation of inhalation reference concentrations and application of inhalation dosimetry. Office of Research and Development, Washington, DC; EPA/600/8-90/066F. Available online at http://www.epa.gov/iris/backgr-d.htm. 4. HAZARD IDENTIFICATION 4.1. STUDIES IN HUMANS—EPIDEMIOLOGY, CASE REPORTS, CLINICAL CONTROLS Alexeeff, G; Deng, KK; Broadwin, R; Salmon, AG. (2006) Benchmark dose evaluation for human irritation. Toxicologist 90:183. Amatuni, VG; Agaronyan, Zh, P. (1980) Chronic bronchitis and pulmonary function in workers of a polyvinyl acetate factory. Gig Tr Prof Zabol 0(2): 14-16. (Russian) Amatuni, VG; Agaronyan, Zh, P. (1987) Diagnosis of chronic bronchitis caused by vinyl acetate and products of its synthesis. Zh Eksp Klin Med 27(2): 167-172. (Russian) Carnegie-Mellon University. (1968) Summary of responses of animals and humans to the vapors of vinyl acetate. Carnegie-Mellon University, Pittsburgh, PA. Carnegie-Mellon Institute. (1992) Initial submission: vinyl acetate: single animal inhalation and human sensory response with cover letter dated 08/27/92. Union Carbide Corporation, Danbury, CT; 88-920010328; OTS0571724. Available online at http s: //ntrl. nti s. gov/ search/TRLProductDetail. aspx? ABBR=OT S0571724. A-5 DRAFT - DO NOT CITE OR QUOTE ------- Deese, DE; Joyner, RE. (1969) Vinyl acetate: a study of chronic human exposure. Am Ind Hyg Assoc J 30:449-457. Korosteleva, TA; Shmidt, AV. (1989) Oncological risk factors and cancer in resin industry workers. Vopr Onkol (Leningr) 35(5):536-544. Leffingwell, SS; Waxweiler, R; Alexander, V; et al. (1983). Case-control study of gliomas of the brain among workers employed by a Texas City, Texas chemical plant. Neuroepidemiology 2:179-195. Maltoni, C. (1976) Occupational carcinogenesis. Predictive value of carcinogenesis bioassays. Ann NY Acad Sci 271:431-443. Ott, MG; Teta, MJ; Greenberg, HL. (1989) Lymphatic and hematopoietic tissue cancer in a chemical manufacturing environment. Am J Ind Med 16(6):631-43. Prisyazhnyuk, VE. (1971) Study of the toxic effect of vinyl acetate and acetaldehyde in the atmosphere. Gig Sanit 36(12): 13-16. Ramirez, JA; Arismendi, G; Cedillo, L; et al. (1990) Advances in a psychodiagnostic test battery for Mexican workers exposed to toxic substances in the petrochemical and other industries. In: Johnson, BL; ed. Advances in neurobehavioral toxicology: applications in environmental and occupational health. Third International Symposium on Neurobehavioral Methods in Environmental and Occupational Health, Washington, DC, USA, December 14-17, 1988. Chelsea, MI: Lewis Publishers; pp. 96-106. Ray, PK; Prasad, AK. (1987) Environmental carcinogens and immune functions of the host. J Sci Ind Res (India) 46(4): 162-167. Safety and Fire Protection Committee. (1962) Vinyl acetate explosion and fire—fatality, case history no. 384. In: Safety and fire protection committee, case histories of accidents in the chemical industry. Washington, DC: Manufacturing Chemists' Association 1; pp. 106-107. Sankaranarayanan, R; Wahrendorf, J; Demaret, E. (1994) IARC scientific publications 130. Directory of on-going research in cancer epidemiology. International Agency for Research on Cancer, Lyon, France. Santodonato, J; Bosch, S; Meylan, W; et al. (1985) Monograph on human exposure to chemicals in the workplace: vinyl acetate. Center for Chemical Hazard Assessment, Syracuse Research Corporation, Syracuse, NY; Report No.SRC-TR-85.-190: 43. Talakina, EI; Rachkovskaya, LV; Skorokhod, LP. (1977) Health protection of pregnant women engaged in the production of acetylene vinyl acetate. Gig Tr Prof Zabol 3:46-47. Takeshita, T; Suminori, K. (2000) Relationships between cigarette smoking, alcohol drinking, the ALDH2 genotype and adenomatous types of colorectal polyps in male self-defense force officials. J Epidemiol 10(6):366-71. A-6 DRAFT - DO NOT CITE OR QUOTE ------- Union Carbide Corporation. (1989a) Lymphatic and hematopoietic tissue cancer in a chemical manufacturing environment and a mortality study of men assigned to ethylene oxide production or other related chemical manufacturing with letter 08/17/89. Union Carbide Corporation, Danbury, CT; 89-890000225; OTS0513414-3. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS05134143. Union Carbide Corporation. (1989b) Lymphatic and hematopoietic tissue cancer in a chemical manufacturing environment with attached tables and cover letter dated 02/21/89. Union Carbide Corporation, Danbury, CT; 89-890000005; 89890000092; OTS0513414-2. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS05134142. Vervalin, CH; ed. (1964) Chicago vinyl acetate incident. In: Fire protection. Manual for hydrocarbon processing plants. Houston, TX: Gulf Publishing Co.; p. 358. Waxweiler, RJ. (1981) Epidemiologic problems associated with exposure to several agents. 1st Annual Symposium on Environmental Epidemiology, Pittsburgh, PA, USA, April 28-30, 1980. Environ Health Perspect 42:51-56. Zeisler, EP. (1940) Dermatitis from elasti-glass garters and wrist watch straps. J Am Med Assoc 14(26):2540-2542. 4.2. SUBCHRONIC AND CHRONIC STUDIES AND CANCER BIOASSAYS IN ANIMALS—ORAL AND INHALATION Beems, RB. (1988) Histopathology of the respiratory tract of mice used in a 104-week inhalation study with vinyl acetate with cover letter dated 04/06/90. Civo Institute Tno, Zeist, The Netherlands; 86900000411; OTS0522974. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS0522974. Bogdanffy, MS (2002). Vinyl acetate-induced intracellular acidification: implications for risk assessment. Toxicol Sci 66:320-326. Bogdanffy, MS; Dreef-van der Meulen, HC; Beems, RB; et al. (1994a) Chronic toxicity and oncogenicity inhalation study with vinyl acetate in the rat and mouse. Fundam Appl Toxicol 23:215-229. Bogdanffy, MS; Tyler, TR; Vinegar, MB; et al. (1994b) Chronic toxicity and oncogenicity study with vinyl acetate in the rat: in utero exposure in drinking water. Fundam Appl Toxicol 23:206- 214. Bogdanffy, MS; Gladnick, NL; Kegelman, T; et al. (1997) Four week inhalation cell proliferation study of the effects of vinyl acetate on rat nasal epithelium, with cover letter dated 2/26/1997. E.I. du Pont de Nemours and Co., Inc., Newark, DE. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS0558940. Clary, JJ. (1988) Chronic and reproduction toxicologic studies on vinyl acetate. Status report. Ann NY Acad Sci 534:255-260. Czajkowska, T; Sokal, J; Knobloch, K; et al. (1986) Experimental study on chronic toxic effect A-7 DRAFT - DO NOT CITE OR QUOTE ------- of vinyl acetate. Med Pr 37(l):26-36. Experimental Pathology Laboratories, Inc. (1982) Bioassay of vinyl acetate in F344 rats: pathology report addendum [with cover letter dated 09/30/82 and EPA response dated 10/13/82], Experimental Pathology Associates, Research Triangle Park, NC; FYIAX10820197SUP. Gale, EP. (1979) Vinyl acetate: 4 week oral (drinking water) dose range-finding study in the rat and mouse. U.S. EPA/OTS public files. Hazleton Labs Europe, Ltd; Document no. FYI-OTS- 0184-0278. Gale, EP. (1980a) Vinyl acetate: 3 month oral (drinking water) toxicity study in the mouse. U.S. EPA/OTS public files. Hazleton Labs Europe, Ltd.; document no. FYI-OTS-0184-0278. Gale, EP. (1980b). Vinyl acetate: 3 month oral (drinking water) toxicity study in the rat. Society of the Plastics Industry Inc., New York. Available online at http://www.ntis.gov/search/product.aspx?ABBR=OTS00002780. Hazelton Laboratories. (1987) Letter to report preliminary pathology results from the terminal sacrifice of rats at the end of a two year inhalation study of vinyl acetate. Hazleton Laboratories America, Inc., Rockville, MD; 88870000018; OTS0510664. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS0510664. Hazelton Laboratories. (1989a) Vinyl acetate: 104 week inhalation combined chronic toxicity and carcinogenicity study in the rat and mouse (vol. I, II, and IV) and (vol. I of amendment to final report) with letter 01/31/89. Hazelton Laboratories, North Yorkshire, England; 89- 890000088; OTS0510582-3. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS05105823. Hazelton Laboratories. (1989b) Vinyl acetate: 104 week inhalation combined chronic toxicity and carcinogenicity study in the rat and mouse volumes I-IV with cover letter dated 01/31/89. Hazelton Laboratories, North Yorkshire, England; 86-890000107; OTS0517446. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS0517446. Hurtt, ME; Vinegar, MB; Rickard, RW; et al. (1995) Developmental toxicity of oral and inhaled vinyl acetate in the rat. Fundam Appl Toxicol 24:198-205. Japan Bioassay Research Center. (1995) Report on carcinogenicity studies on vinyl acetate orally administered (mixed in drinking water) to rats and mice. Japan Industrial Safety and Health Association, Japan; FYIOTS02971286. Japan Bioassay Research Center. (2002) Initial submission: report on carcinogenicity studies on vinyl acetate orally administered (mixed in drinking water) to rats and mice (Japanese) with English translation and cover letter dated 04/23/02. Japan Bioassay Research Center, Japan; 88020000132. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS0574372. Lijinsky, W. (1988) Chronic studies in rodents of vinyl acetate and compounds related to acrolein. Ann NY Acad Sci 534:246-254. A-8 DRAFT - DO NOT CITE OR QUOTE ------- Lijinsky, W; Reuber, MD. (1983) Chronic toxicity studies of vinyl acetate in Fischer rats. Toxicol Appl Pharmacol 68:43-53. Maltoni, C; Ciliberti, A; Lefemine, G; et al. (1997) Results of a long-term experimental study on the carcinogenicity of vinyl acetate monomer in mice. Ann NY Acad Sci 837:209-238. Mebus, CA; Carpanini, FMB; Rickard, RW; et al. (1998) A two-generation reproduction study in rats receiving drinking water containing vinyl acetate. Fundam Appl Toxicol 24:206-216. Minardi, F; Belpoggi, F; Soffritti, M; et al. (2002) Results of long-term carcinogenicity bioassay on vinyl acetate monomer in Sprague-Dawley rats. Ann NY Acad Sci 982:106-122. Monsanto Company. (1989) Health effects assessments for vinyl acetate at the Trenton and Decatur Plants (final reports) with attachments, cover sheets and letter dated 122889. Monsanto Company; U.S. EPA/OPTS Fiche #: OTS0521596, Doc#: 86-900000047. Morris, JB. (1997) Dosimetry, toxicity and carcinogenicity of inspired acetaldehyde in the rat. MutatRes 380(1-2): 113-124. NCI (National Cancer Institute). (1982a) Bioassay of vinyl acetate in F344 rats pathology report addendum. U.S. EPA/OTS public files. National Cancer Institute, Bethesda, MD; FYI-AX- 1082-0197. Owen, PE. (1979a) Vinyl acetate: 4 week inhalation dose ranging study in the mouse. Hazleton Laboratories Europe, Ltd., England; submitted by the Society of the Plastics Industry Inc., New York; U.S. EPA Document No. FYI-OTS-0184-0278SU, Fiche No. OTS0278. Owen, PE (1979b). Vinyl acetate: 4 week inhalation dose ranging study in the rat. Hazleton Laboratories Europe, Ltd., England; submitted by the Society of the Plastics Industry Inc., New York; U.S. EPA Document No. FYI-OTS-0184-0278SU, Fiche No. OTS0278. Owen, PE. (1980a) Vinyl acetate: 3 month inhalation toxicity study in the rat. Hazleton Laboratories Europe, Ltd., England; submitted by the Society of the Plastics Industry Inc., New York; U.S. EPA Document No. FYI-OTS-0184-0278SU, Fiche No. OTS0278. Available online at http://www.ntis.gov/search/product.aspx?ABBR=OTS00002780. Owen, PE. (1980b) Vinyl acetate: 3 month inhalation toxicity study in the mouse. Hazleton Laboratories Europe, Ltd., Harrogate, England; submitted by the Society of the Plastics Industry, Inc., New York; Report No. 2303-51/5. Owen, PE. (1988) Vinyl acetate: 104 week inhalation combined chronic toxicity and carcinogenicity study in the rat and mouse. Hazleton Laboratories Europe, Ltd., Harrogate, England; submitted by the Society of the Plastics Industry, Inc., New York; report No. 5547- 51/15. Prisyazhnyuk, VE. (1971) Toxic effect of simultaneous exposure to vinyl acetate and acetaldehyde in air. Gigiena i Sanitariya 36(12):344-349. Soffritti, M; Belpoggi, F; Cevolani, D; et al. (2002) Results of long-term experimental studies on A-9 DRAFT - DO NOT CITE OR QUOTE ------- the carcinogenicity of methyl alcohol and ethyl alcohol in rats. Ann NY Acad Sci. 982:46-69. SPI (Society of the Plastics Industry). (1987) Letter to report preliminary pathology results from the terminal sacrifice of rats at the end of a two year inhalation study of vinyl acetate. U.S. EPA/OTS public files. Society of the Plastics Industry, Inc., New York; document no. 8EHQ- 0187-0650. Strong, HA; Cresswell, DG; Hopkins, R. (1980) Investigations into the metabolic fate of vinyl acetate in the rat and mouse: part 2. Society of the Plastics Industry, Inc., New York. Available online at http://www.ntis.gov/search/product.aspx?ABBR=OTS00002780. Tiunova, LV; Rumyantsev, AP. (1975) Changes in rhythm of liver enzyme activity in albino rats during chronic exposure to vinyl acetate. Byulleten' Eksperimental'noi Biologii i Meditsiny 79(4):101-103. TNO-CIVO Institutes. (1989) Histopathology of the respiratory tract of rats used in a 104 week inhalation study with vinyl acetate with attachments and cover letter dated 07/03/89. TNO- CIVO Institutes, Zeist, The Netherlands; 86-890000937; OTS0520375; V 88.033/270836. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS0520375. Umeda, Y; Matsumoto, M; Yamazaki, K; et al. (2004) Carcinogenicity and chronic toxicity in mice and rats administered vinyl acetate monomer in drinking water. J Occup Health 46:87-99. U.S. EPA (Environmental Protection Agency). (1989) Health and environmental effects document for vinyl acetate. U.S. Environmental Protection Agency, Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Cincinnati, OH; ECAO- CIN-G067. U.S. EPA (Environmental Protection Agency). (1997) Carcinogenesis study of vinyl acetate (drinking water study) in rats and mice, with cover letter from Japan Bioassay Research Center (01/31/1997). Environmental Protection Agency, Washington, DC; FYI-OTS-0297-1286. Valentine, R; Bamberger, JR; Szostek, B; et al. (2002) Time- and concentration-dependent increases in cell proliferation in rats and mice administered vinyl acetate in drinking water. Toxicol Sci 67:190-197. 4.3. REPRODUCTIVE/DEVELOPMENTAL STUDIES—ORAL AND INHALATION Bogdanffy, MS; Tyler, TR; Vinegar, MB; et al. (1994) Chronic toxicity and oncogenicity study with vinyl acetate in the rat: in utero exposure in drinking water. Fund Appl Toxicol 23(2):206- 214. Clary, JJ. (1988) Chronic and reproduction toxicologic studies on vinyl acetate. Status report. Ann NY Acad Sci 534:255-260. Hazleton Laboratories. (1988) Vinyl acetate: oral (drinking water) 2 generation reproduction study in rat with attachments and cover letter dated 05/23/88. Hazleton Laboratories Europe, Ltd., North Yorkshire, England; 89-880000181; OTS0510582-2. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS05105822. A-10 DRAFT - DO NOT CITE OR QUOTE ------- Hazleton Laboratories. (1992) Initial submission: vinyl Acetate: oral (drinking water) 2 generation reproduction study in the rat with cover letter dated 04/10/92. Hazleton Laboratories Europe, Ltd., North Yorkshire, England; 88-920001915; OTS0539369. Available online at https://ntrl.ntis. gov/search/TRLProductDetail.aspx?ABBR=OTS0539369. Hazleton Laboratories. (1992) Initial submission: vinyl acetate: oral and inhalation teratology studies in the rat (summary report) with cover letter dated 01/14/92. Hazleton Laboratories Europe, Ltd., North Yorkshire, England; 88-920000604; OTS0535164. Available online at http s: //ntrl. nti s. gov/ search/TRLProductDetail. aspx? ABBR=OT S0535164. Hurtt, ME; Vinegar, MB; Rickard, RW; et al. (1995) Developmental toxicity of oral and inhaled vinyl acetate in the rat. Fundam Appl Toxicol 24:198-205. Irvine, LFH. (1980) Vinyl acetate oral and inhalation teratology studies in the rat. Hazleton Laboratories Europe Ltd., North Yorkshire, England, for the Society of the Plastics Industry, Inc., New York; report No. 2195-51/6&7. Lahdetie, J. (1988) Effects of vinyl acetate and acetaldehyde on sperm morphology and meiotic micronuclei in mice. Mutat Res 202:171-178. Monsanto Company. (1989) Health effects assessment for vinyl acetate at the Decatur plant 7 (final report) with attachment and cover letter dated 12/28/89. EPA/OTS; doc 8 #86-900000050. Mebus, CA; Carpanini, FMB; Rickard, RW; et al. (1998) A two-generation reproduction study in rats receiving drinking water containing vinyl acetate. Fundam Appl Toxicol 24:206-216. Rodwell, DE, Kelly, CM; et al. (2002). Effects of polyvinyl alcohol administered in the diet to rats on fertility, early embryonic development, growth and development. Toxicologist 66(1- S):375. Shaw, DC. (1987) Vinyl acetate: oral (drinking water) 2 generation reproduction study in the rat. Hazleton Laboratories Europe Ltd., North Yorkshire, England, for the Society of Plastics Industry, Inc., New York; report No. 4661-5 l/17a; 91 pp. SPI (Society of the Plastics Industry). (1985) Summary of preliminary findings of a 2 generation reproductive study in rats with cover letter. U.S. EPA/OTS public files. Society of the Plastics Industry, Inc., New York; document no. OTS0509716; 8EHQ-0185-0543. Soffritti, M; Belpoggi, F; Esposti, DD; et al. (2008) Consequences of exposure to carcinogens beginning during developmental life. Basic Clin Pharmacol Toxicol 102:118-124. Ye, WP; Gu, ZW; et al. (1992) Occlusive or non-occlusive methods of vas deferens in males. Adv Contracept Del Sys: CDS 8(1-2):41—51. Unknown (1988) Vinyl acetate: 104 week oral (drinking water) combined chronic toxicity and carcinogenicity study in the rat following in utero exposure (volume I, II, and III) with cover letter 05/23/88. EPA/OTS; 86880000265; OTS0514156. Available online at A-ll DRAFT - DO NOT CITE OR QUOTE ------- http s: //ntrl. nti s. gov/ search/TRLProductDetail. aspx? ABBR=OT S0514156. 4.4. OTHER DURATION- OR ENDPOINT-SPECIFIC STUDIES Bartenev, VD. (1957) The effect of vinyl acetate on the central nervous system of rabbits. Gig Tr Prof Zabol 8:63-66. Biodynamics Inc. (1992b) Initial submission: letter from Monsanto Co. to US EPA regarding toxicity studies of vinyl acetate/maleate/acrylate copolymer solution with attachments and cover letter dated 08/13/1992. Monsanto Company, St. Louis, MO; 8EHQ089210239; OTS0570821. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS0570821. Biodynamics, Inc. (1992c) Initial submission: eye and dermal irritation studies in rabbits with cover letter dated 08/13/92. Biodynamics, Inc., Worcester, MA; 88-920007373; OTS0538508. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS0538508. Carnegie-Mellon University. (1968) Summary of responses of animals and humans to the vapors of vinyl acetate. Carnegie-Mellon Univesity, Pittsburgh, PA. Carpenter, CP; Smyth, HF Jr; Pozzani, UC. (1949) The assay of acute vapor toxicity, and the grading and interpretation of results on 96 chemical compounds. J Ind Hyg Toxicol 31:343-346. Celanese Chemical Company, Inc. (1983) Primary skin irritation tests with eighteen materials in albino rabbits with cover letter. Celanese Chemical Company, Inc., Dallas, TX; OTS-0206028; 878212151. Available online at https ://ntrl .ntis.gov/search/TRLProductDetail. aspx? ABBR=OTS0206028. Cornish, HH; Abar, EL. (1919) Toxicity of pyrolysis products of vinyl plastics. Arch Env Health 19:15-21. Czajkowska, T; Sokal, J; Knobloch, K; et al. (1986) Experimental studies of acute and chronic toxic effects of vinyl acetate. Med Pr 37(l):26-36. Gage, JC. (1970) The subacute inhalation toxicity of 109 industrial chemicals. Brit J Ind Med 27:1-18. Goldstein, I; David, V; Rotaru, G. (1927) Experimental research on the combined action of vinyl acetate and acetic acid. Scientific Session of the Institute of Public Health, Bucharest; 19681968. Hill Top Biolabs, Inc. (1995) Delayed contact hypersensitivity study in guinea pigs (Buehler technique) of: vinyl acetate with cover letter dated 05/10/95. Hill Top Biolabs, Inc., Cincinnati, OH; 86950000263. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx? ABBR=OTS0572569. Industrial Bio-Test Laboratories. (1972) Primary skin irritation tests with eighteen materials in albino rabbits (with cover letter). U.S. EPA/OTS public files. Industrial Bio-Test Laboratories, Inc., Northbrook, IL; document no. 878212151. A-12 DRAFT - DO NOT CITE OR QUOTE ------- Industrial Bio-Test Labs, Inc. (1989) Primary skin irritation tests with eighteen materials in albino rabbits with cover letter dated 06/15/89. Hoechst Celanese Corporation, Dallas, TX; 86- 890001277; OTS0520783. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS0520783. Industrial Bio-Test Laboratories. (1991) Letter concerning enclosed primary skin irritation test and air quality dispersion modeling report with attachments. Industrial Bio-Test Laboratories, Inc., Northbrook, IL; 86-920000433; OTS0534489. Available online at http s: //ntrl. nti s. gov/ search/TRLProductDetail. aspx? ABBR=OT S0534489. Kennedy, GL, Jr; Graepel, GJ. (1991) Acute toxicity in the rat following either oral or inhalation exposure. Toxicol Lett 56:317-326. Smyth, HF; Carpenter, CP. (1973) Initial submission: vinyl acetate: single animal inhalation and human sensory response with cover letter dated 082792. Carnegie-Mellon Institute, Pittsburgh, PA. Submitted by Union Carbide Corporation; doc. # 88-920010328. 4.5.1. MECHANISTIC DATA AND OTHER STUDIES IN SUPPORT OF THE MODE OF ACTION Bogdanffy, MS; Jarabek, AM. (1995) Understanding mechanisms of inhaled toxicants: implications for replacing default factors with chemical-specific data. Toxicol Lett 82(83):919- 932. Bogdanffy, MS; Plowchalk, DR; Sarangapani, R; et al. (2001). Mode-of-action-based dosimeters for interspecies extrapolation of vinyl acetate inhalation risk. Inhal Toxicol 13(5):377-396. Glatt, CM; Ewane, KA; Nabb, DL; et al. (2004) In vitro gene expression profiling of hepatotoxins using DNA microarrays. Toxicologist 78(1-S):404. Ub, I. (1983). Effect of vinyl acetate on the microsomal enzyme activity of the liver of rats. Przegl Lek 40(6):515-516. (Polish) 4.5.2.1. MUTAGENICITY Bartsch, H; Malaveille, C; Montesano, R; et al. (1976) Predictive value of tissue-mediated mutagenicity assays to assess the carcinogenic risk of chemicals. IARC (Internal Agency for Research on Cancer) Sci Publ 12:467-491. Bartsch, H; Malaveille, C; Barbin, A; et al. (1979) Mutagenic and alkylating metabolites of halo- ethylenes, chlorobutadienes and dichlorobutenes produced by rodent or human liver tissues: Evidence for oxirane formation by P450-linked microsomal mono-oxygenases. Arch Toxicol 41:249-277. Bartsch, H; Malaveille, C; Camus, A-M; et al. (1980) Validation and comparative studies on 180 chemicals with S. typhimurium strains and V79 Chinese hamster cells in the presence of various metabolizing systems. Mutat Res 76:1-50. Brams, A; Buchet, JP; Crutzen-Fayt, MC; et al. (1987) A comparative study, with 40 chemicals, of the efficiency of the Salmonella assay and the SOS chromotest (kit procedure). Toxicol Lett A-13 DRAFT - DO NOT CITE OR QUOTE ------- 38:123-133. Em inert, B; Biinger, J; Keuch, K; et al. (2006) Mutagenicity of cytochrome P450 2E1 substrates in the Ames test with the metabolic competent S. typhimurium .strain YG7108pin3ERb5. Toxicology 228:66-76. Florin, I; Rutberg, L; Curvall, M; et al. (1980) Screening of tobacco smoke constituents for mutagenicity using the Ames' test. Toxicology 15:219—232. Helander, A. (1991) Increased frequency of acetaldehyde-induced sister-chromatid exchanges in human-lymphocytes treated with an aldehyde dehydrogenase inhibitor. Mutat Res 264(3): 103- 107. Hengstler, JG; Bogdanffy, MS; Bolt, HM; et al. (2003) Challenging dogma: thresholds for genotoxic carcinogens? The case of vinyl acetate. Annu Rev Pharmacol Toxicol 43:485-520. Jantunen, K., Maki-Paakkanen, J; Norppa, H. (1986) Induction of chromosome aberrations by styrene and vinyl acetate in cultured human lymphocytes: dependence on erythrocytes. Mutat Res 159(1-2). Kim, JS; Kim, YJ; Kim, TY; et al. (2005) Association of ALDH2 polymorphism with sensitivity to acetaldehyde-induced micronuclei and facial flushing after alcohol intake. Toxicology 210(2- 3):169-174. Kuykendall, JR; Taylor, ML; Bogdanffy, MS. (1993) DNA-protein crosslink formation in isolated rat nasal epithelial cells exposed to vinyl acetate and acetaldehyde [abstract]. Presented at 84th Annual Meeting of the American Association for Cancer Research, Orlando, FL. Kuykendall, JR; Bogdanffy, MS. (1992) Reaction kinetics of DNA-histone crosslinking by vinyl acetate and acetaldehyde. Carcinogenesis 13(11):2095—2100. Lahdetie, J. (1988) Effects of vinyl acetate and acetaldehyde on sperm morphology and meiotic micronuclei in mice. Mutat Res 202:171-178. Lahdetie, J. (1990) Genotoxicity assays of vinyl acetate and acetaldehyde in male germ cells of mice. Mutat Res 234:389-390. Lambert, B; Chen, Y; He, S-M; et al. (1985) DNA cross-links in human leucocytes treated with vinyl acetate and acetaldehyde in vitro. Mutat Res: DNA Repair 146:301-303. Lijinsky, W; Andrews, AW. (1980) Mutagenicity of vinyl compounds in Salmonella typhimurium. Teratog Carcinog Mutagen 1:259-267. Maki-Paakkanen, J; Norppa, H. (1987) Induction of micronuclei by vinyl acetate in mouse bone marrow cells and cultured human lymphocytes. Mutat Res 190(1):41—45. McCann, J; Choi, E; Yamasaki, E; Ames, BN. (1975) Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals. PNAS 72:5 135-5 139. A-14 DRAFT - DO NOT CITE OR QUOTE ------- Monsanto Company. (1989) Health effects assessment for vinyl acetate at the Decatur plant 7 (final report) with attachment and cover letter dated 12/28/89. EPA/OTS; doc 8 #86-900000050. Norppa, H; Maki-Paakkanen, J; Jantunen, K; et al. (1988) Mutagenicity studies on styrene and vinyl acetate. Ann NY Acad Sci 534:671-678. Simon, P; Ottenwalder, H; Bolt, HM. (1985) Vinyl acetate: DNA-binding assay in vivo. Toxicol Lett 27(1-3): 115-120. Vainio, H; Waters, HM; Norppa, H. (1985) Mutagenicity of selected organic solvents. Scand J Work Environ Health 11:75-82. 4.5.2.2. GENOTOXICITY AND CLASTOGENICITY Bogdanffy, MS; Valentine, R. (2003) Differentiating between local cytotoxicity, mitogenesis, and genotoxicity in carcinogen risk assessments: the case of vinyl acetate. Toxicol Lett 140- 141:83-98. Bolt, HM. (1988) Roles of etheno-DNA adducts in tumorigenicity of olefins. Crit Rev Toxicol 18(4):299-309. Bolt, HM. (2003) Genotoxicity-threshold or not? Introduction of cases of industrial chemicals. Toxicol Lett 140-141:43-51. Brooks, PJ. (2005) DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis. Alcohol 35(3): 187-193. He, S-M; Lambert, B. (1985) Induction and persistence of SCE-inducing damage in human lymphocytes exposed to vinyl acetate and acetaldehyde in vitro. Mutat Res 158:201-208. Hengstler, JG; Bogdanffy, MS; Bolt, HM; et al. (2003) Challenging dogma: thresholds for genotoxic carcinogens? The case of vinyl acetate. Annu Rev Pharmacol Toxicol 43:485-520. Kuykendall, JR.; Bogdanffy, MS (1992). Reaction kinetics of DNA-histone crosslinking by vinyl acetate and acetaldehyde. Carcinogenesis 13:2095-2100. Kuykendall, JR.; Taylor, ML; Bogdanffy, MS. (1993) Cytotoxicity and DNA-protein crosslink formation in rat nasal tissues exposed to vinyl acetate are carboxylesterase-mediated. Toxicol Appl Pharmacol 123:283-292. Maki-Paakkanen, J; Norppa, H. (1987) Induction of micronuclei by vinyl acetate in mouse bone marrow cells and cultured human lymphocytes. Mutat Res 190:41-45. Monsanto Company. (1989) Health effects assessment for vinyl acetate at the Decatur plant 7 (final report) with attachment and cover letter dated 12/28/89. EPA/OTS; doc 8 #86-900000050. Norppa, H; Tursi, F. (1984) Erythrocyte-mediated metabolic activation detected by SCE, in: Sister chromatid exchanges: 25 years of experimental research, partb: genetic toxicology and A-15 DRAFT - DO NOT CITE OR QUOTE ------- human studies. Basic Life Sci 29B:547-559. Norppa, H; Tursi, F; Pfaffli, P; et al. (1985) Chromosome damage induced by vinyl acetate through in vitro formation of acetaldehyde in human lymphocytes and Chinese hamster ovary cells. Cancer Res 45:4816-4821. Norppa, H; Maki-Paakkanen, J; Jantunen, K; et al. (1988) Mutagenicity studies on styrene and vinyl acetate. Ann NY Acad Sci 534:671-678. Simon, P; Epe, B; Schiffmann, D; et al. (1986) Synthesis and genotoxicity of acetoxyoxirane the epoxide of vinyl acetate. J Biochem Toxicol 1:43-56. Sipi, P; Jarventaus, H; Norppa, H. (1992) Sister-chromatid exchanges induced by vinyl esters and respective carboxylic acids in cultured human lymphocytes. Mutat Res 279(2):75-82. Takeshita, T; Iijima, S; Higurashi, M. (1986) Vinyl acetate-induced sister chromatid exchanges in murine bone marrow cells. Proceedings of the Japan Academy, Series B Physical and Biological Sciences 62:239-242. Tucker, JD; Auletta, A; Cimino, MC; et al. (1993) Sister-chromatid exchange: second report of the Gene-Tox Program. Mutat Res 297(2): 101-180. Union Carbide Corporation. (1989a) Lymphatic and hematopoietic tissue cancer in a chemical manufacturing environment and a mortality study of men assigned to ethylene oxide production or other related chemical manufacturing with letter 08/17/89. Union Carbide Corporation, Danbury, CT; 89-890000225; OTS0513414-3. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS05134143. Union Carbide Corporation. (1989b) Lymphatic and hematopoietic tissue cancer in a chemical manufacturing environment with attached tables and cover letter dated 02/21/89. Union Carbide Corporation, Danbury, CT; 89-890000005; 89890000092; OTS0513414-2. Available online at https://ntrl.ntis.gov/search/TRLProductDetail.aspx?ABBR=OTS05134142. 4.5.2.3. INTRACELLULAR ACIDIFICATION FOLLOWING EXPOSURE TO VINYL ACETATE AND OTHER NON-GENOTOXIC STUDIES Buoen, LC. (1975) Foreign-body tumorigenesis: in vitro isolation and expansion of preneoplastic clonal cell populations. J Natl Cancer Inst 55(3):721-3. Feron, VJ. (1991) Aldehydes - occurrence, carcinogenic potential, mechanism of action and risk assessment. Mutat Res 259(3-4):363-385. Genter, M. (2004) Olfactory mucosal metabolic enzymes: modulation of toxic endpoints based on distribution, induction, and age-and species variables. Toxicologist 78(1-S): 193. Laib, RJ; Bolt, HM. (1986) Vinyl acetate a structural analog of vinyl carbamate fails to induce enzyme altered foci in rat liver. Carcinogenesis 7:841-843 Lantz, RC; Orozco, J; Bogdanffy, MS. (2003) Vinyl acetate decreases intracellular pH in rat A-16 DRAFT - DO NOT CITE OR QUOTE ------- nasal epithelial cells. Toxicol Sci 75(2):423-432. Nakamoto, T; Wagner, M; Melvin, JE; et al. (2005) Vinyl acetate induces intracellular acidification in mouse oral buccal epithelial cells. Toxicol Lett 158(2): 116—121. Roberts, ES; Wong, VA; McManus, BE; et al. (2005) Hydrogen sulfide exposure causes intracellular acidification of rat nasal respiratory epithelial cells. Toxicol Sci 84(1-S):192. Roberts, ES; Soucy, NV; Bonner, AM; et al. (2006) Normal gene expression in male and female Sprague Dawley rat nasal respiratory and olfactory epithelia. Toxicol Sci 90(1-S): 133. Slikker, JW, Andersen, ME; Bogdanffy, MS; et al. (2004) Dose-dependent transitions in mechanisms of toxicity: case studies. Toxicol Appl Pharmacol 201(3):226-294. Union Carbide Corporation. (1992) Initial submission: letter from Union Carbide Corp to U.S. EPA regarding an in vitro viral oncogenesis study of vinyl acetate in hamster embryo cells with cover letter dated 08/27/92. Union Carbide Corporation, Danbury, CT; EPA-OTS-88- 920009502; OTS0571158. Available online at http s: //ntrl. nti s. gov/ search/TRLProductDetail. aspx? ABBR=OT S0571158. Valentine, R; Bamberger, JR; Szostek, B; et al. (2002) Time- and concentration-dependent increases in cell proliferation in rats and mice administered vinyl acetate in drinking water. Toxicol Sci 67:190-197. 4.6. SYNTHESIS OF MAJOR NONCANCER EFFECTS 4.6.1. Oral 4.6.2. Inhalation 4.6.3. Mode of Action Information 4.7. EVALUATION OF CARCINOGENICITY 4.7.1. Summary of Overall Weight of Evidence 4.7.2. Synthesis of Human, Animal, and Other Supporting Evidence 4.7.3. Mode-of-Action Information 4.8. SUSCEPTIBLE POPULATIONS AND LIFE STAGES 5. DOSE-RESPONSE ASSESSMENTS 5.1. ORAL REFERENCE DOSE (RfD) 5.1.1. Choice of Principal Study and Critical Effect—with Rationale and Justification 5.1.2. Methods of Analysis—Including Models (PBPK, BMD, etc.) 5.1.3. RfD Derivation—Including Application of Uncertainty Factors (UFs) 5.1.4. RfD Comparison Information [Note: include this section only if multiple "RjDs " have been developed] 5.1.5. Previous RfD Assessment [Note: include a short description of the previous assessment or provide text to indicate that an RfD was not previously on IRIS] 5.2. INHALATION REFERENCE CONCENTRATION (RfC) 5.2.1. Choice of Principal Study and Critical Effect—with Rationale and Justification 5.2.2. Methods of Analysis—Including Models (PBPK, BMD, etc.) 5.2.3. RfC Derivation—Including Application of Uncertainty Factors (UFs) A-17 DRAFT - DO NOT CITE OR QUOTE ------- 5.2.4. RfC Comparison Information [Note: include this section only if multiple "RfCs" have been developed] 5.2.5. Previous RfC Assessment [Note: include a short description of the previous assessment or text to indicate that an RfC was not previously on IRIS] 5.3 UNCERTAINTIES IN THE ORAL REFERENCE DOSE AND INHALATION REFERENCE CONCENTRATION 5.4. CANCER ASSESSMENT 5.4.1. Choice of Study/Data—with Rationale and Justification 5.4.2. Dose-response Data 5.4.3. Dose Adjustments and Extrapolation Method(s) [Note: include rationale for choice of method(s), and implications, if any, of MO A information on quantitation] 5.4.4. Oral Slope Factor and Inhalation Unit Risk 5.4.5. Uncertainties in Cancer Risk Values 5.4.6. Previous Cancer Assessment [Note: include a short description of the previous cancer quantitation or provide text to indicate that cancer quantitation was not previously on IRIS] 6. MAJOR CONCLUSIONS IN THE CHARACTERIZATION OF HAZARD AND DOSE RESPONSE 6.1. HUMAN HAZARD POTENTIAL 6.2. DOSE RESPONSE A-18 DRAFT - DO NOT CITE OR QUOTE ------- |