Ethyl carbamate in fermented beverages: Presence, analytical chemistry, formation mechanism, and mitigation proposals

Comprehensive Reviews in Food Science and Food Safety

Volumn 13, Issue 4, 2014, Pages 611-626

  Jiao, Zhihua ^a   Dong, Yachen ^a   Chen, Qihe ^a  

^a ZHEJIANG UNIVERSITY   (China)

Author keywords

Analytical methods; Ethyl carbamate; Formation pathways; Genotoxicity; Mitigation strategies

Indexed keywords

ARGININE; CARCINOGENS; FERMENTATION; LACTIC ACID; METABOLISM; UREA; YEAST;

ANALYTICAL METHOD; ETHYL CARBAMATE; FORMATION PATHWAYS; GENOTOXICITIES; MITIGATION STRATEGY;

BEVERAGES;

EID: 84902970278     PISSN: None     EISSN: 15414337     Source Type: Journal    
DOI: 10.1111/1541-4337.12084     Document Type: Review

References (196)

1. Adams C, van Vuuren HJ. 2010. Effect of timing of diammonium phosphate addition to fermenting grape must on the production of ethyl carbamate in wine. Am J Enol Viticult 61(1):125-9.
2. Ajtony Z, Szoboszlai N, Bencs L, Viszket E, Mihucz VG. 2013. Determination of ethyl carbamate in wine by high performance liquid chromatography. Food Chem 141(2):1301-5.
3. Alberts P, Stander MA, De Villiers A. 2011. Development of a novel solid-phase extraction, LC-MS/MS method for the analysis of ethyl carbamate in alcoholic beverages: application to South African wine and spirits. Food Addit Contam A 28(7):826-39.
4. Alcarde A, Souza LD, Bortoletto A. 2012. Ethyl carbamate kinetics in double distillation of sugar cane spirit. J Inst Brewing 118(1):27-31.
5. Alexander J, Auounsson G, Benford D, Cockburn A, Cravedi J, Doglitti E. 2007. Ethyl carbamate and hydrocyanic acid in food and beverages. Scientific opinion of the panel on contaminants. EFSA J 551:1-44.
6. An D, Ough CS. 1993. Urea excretion and uptake by wine yeasts as affected by various factors. Am J Enol Viticult 44(1):35-40.
7. Anderson N, Paul SH, Henry SM. 1943. Induction of pulmonary tumors in mice with ethyl carbamate (urethane). J Natl Cancer Inst 4:309-19.
8. Andrich L, Esti M, Moresi M. 2009a. Urea removal in model wine solutions by immobilized acid urease in a stirred bioreactor. Chem Eng Trans 17:915-20.
9. Andrich L, Esti M, Moresi M. 2009b. Urea degradation in model wine solutions by free or immobilized acid urease in a stirred bioreactor. J Agric Food Chem 57(9):3533-42.
10. Andrich L, Esti M, Moresi M. 2010. Urea degradation kinetics in model wine solutions by acid urease immobilised onto chitosan-derivative beads of different sizes. Enzyme Microb Technol 46(5):397-405.
11. Arena M, Saguir F, Manca de Nadra M. 1999. Arginine, citrulline and ornithine metabolism by lactic acid bacteria from wine. Intl J Food Microbiol 52(3):155-61.
12. Arena ME, Manca de Nadra MC. 2005. Influence of ethanol and low pH on arginine and citrulline metabolism in lactic acid bacteria from wine. Res Microbiol 156(8):858-64.
13. Azevedo Z, Couto J, Hogg T. 2002. Citrulline as the main precursor of ethyl carbamate in model fortified wines inoculated with Lactobacillus hilgardii: a marker of the levels in a spoiled fortified wine. Lett Appl Microbiol 34(1):32-6.
14. Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Bouvard V, Altieri A, Cogliano V. 2007. Carcinogenicity of alcoholic beverages. Lancet Oncol 8(4):292-3.
15. Bauchop T, Elsden S. 1960. The growth of micro-organisms in relation to their energy supply. J Microbiol 23(3):457-69.
16. 1 mice. Food Chem Toxicol 43(1):1-19.
17. Beltran G, Novo M, Rozes N, Mas A, Guillamón JM. 2004. Nitrogen catabolite repression in Saccharomyces cerevisiae during wine fermentations. FEMS Yeast Res 4(6):625-32.
18. Bertrand A. 2003. Utilizzazione dell'ureasi nel vino. In: Vivas N. Prodotti di Trattamento ed Ausiliari di Elaborazione dei Mosti e dei Vini. Reggio Emilia, Italy: Eno-one srl. p 171-92.
19. Boller T, Dürr M, Wiemken A. 1975. Characterization of a specific transport system for arginine in isolated yeast vacuoles. Eur J Biochem 54(1):81-91.
20. Brandriss MC, Magasanik B. 1980. Proline: an essential intermediate in arginine degradation in Saccharomyces cerevisiae. J Bacteriol 143(3):1403-10.
21. Brumley WC, Canas BJ, Perfetti GA, Mossoba MM, Sphon JA, Corneliussen PE. 1988. Quantitation of ethyl carbamate in whiskey, sherry, port, and wine by gas chromatography/tandem mass spectrometry using a triple quadrupole mass spectrometer. Anal Chem 60(10):975-8.
22. Bruno SNF, Vaitsman DS, Kunigami CN, Brasil MG. 2007. Influence of the distillation processes from Rio de Janeiro in the ethyl carbamate formation in Brazilian sugar cane spirits. Food Chem 104(4):1345-52.
23. Cairns T, Siegmund EG, Luke MA, Doose GM. 1987. Residue levels of ethyl carbamate in wines and spirits by gas chromatography and mass spectrometry/mass spectrometry. Anal Chem 59(17):2055-9.
24. Canas BJ, Joe Jr FL, Diachenko GW, Burns G. 1993. Determination of ethyl carbamate in alcoholic beverages and soy sauce by gas chromatography with mass selective detection: collaborative study. J AOAC Intl 77(6):1530-6.
25. Chaillou S, Champomier-Vergès M-C, Cornet M, Crutz-Le Coq A-M, Dudez A-M, Martin V, Beaufils S, Darbon-Rongère E, Bossy R, Loux V. 2005. The complete genome sequence of the meat-borne lactic acid bacterium Lactobacillus sakei 23K. Natl Biotechnol 23(12):1527-33.
26. Cheng M, Conner MK, Alarie Y. 1981. Potency of some carbamates as multiple tissue sister chromatid exchange inducers and comparison with known carcinogenic activities. Cancer Res 41(11 Part 1):4489-92.
27. Chiva R, Baiges I, Mas A, Guillamon JM. 2009. The role of GAP1 gene in the nitrogen metabolism of Saccharomyces cerevisiae during wine fermentation. J Appl Microbiol 107(1):235-44.
28. Christoph N, Bauer-Christoph C. 1998. Maßnahmen zur reduzierung des ethylcarbamatgehaltes bei der Herstellung von Steinobstbränden (II). Kleinbrennerei 50:9-13.
29. Chung SW-C, Kwong KP, Chen BL-S. 2010. Determination of ethyl carbamate in fermented foods by GC-HRMS. Chromatographia 72(5-6):571-5.
30. Claisse O, Lonvaud-Funel A. 2001. Primers and a specific DNA probe for detecting lactic acid bacteria producing 3-hydroxypropionaldehyde from glycerol in spoiled ciders. J Food Protect 64(6):833-7.
31. Conacher HBS, Page BD. 1986. Ethyl carbamate in alcoholic beverages: a Canadian case history. Proceedings of Euro Food Tox II. Switzerland: European Society of Toxicology. p 237-42.
32. Cooper T, Sumrada RA. 1983. What is the function of nitrogen catabolite repression in Saccharomyces cerevisiae? J Bacteriol 155(2):623-7.
33. Cooper TG. 1982. Nitrogen metabolism in Saccharomyces cerevisiae. In: JN Strathern, EW Jones, JR Broach, editors. The molecular biology of the yeast saccharomyces: metabolism and gene expression. Michigan: Cold Spring Harbor. p 680.
34. Cooper TG, Kovari L, Sumrada RA, Park H-D, Luche R, Kovari I. 1992. Nitrogen catabolite repression of arginase (CAR1) expression in Saccharomyces cerevisiae is derived from regulated inducer exclusion. J Bacteriol 174(1):48-55.
35. Cooper TG, Sumrada R. 1975. Urea transport in Saccharomyces cerevisiae. J Bacteriol 121(2):571-6.
36. Coulon J, Husnik JI, Inglis DL, van der Merwe GK, Lonvaud A, Erasmus DJ, van Vuuren HJ. 2006. Metabolic engineering of Saccharomyces cerevisiae to minimize the production of ethyl carbamate in wine. Am J Enol Viticult 57(2):113-24.
37. Dahabieh M, Husnik J, Van Vuuren H. 2010. Functional enhancement of sake yeast strains to minimize the production of ethyl carbamate in sake wine. J Appl Microbiol 109(3):963-73.
38. Dahabieh MS, Husnik JI, van Vuuren HJ. 2009. Functional expression of the DUR3 gene in a wine yeast strain to minimize ethyl carbamate in Chardonnay wine. Am J Enol Viticult 60(4):537-41.
39. Dahl GA, Miller JA, Miller EC. 1978. Vinyl carbamate as a promutagen and a more carcinogenic analog of ethyl carbamate. Cancer Res 38(11 Part 1):3793-804.
40. Davis RH. 1986. Compartmental and regulatory mechanisms in the arginine pathways of Neurospora crassa and Saccharomyces cerevisiae. Microbiol Rev 50(3):280-313.
41. de Orduña RM, Patchett ML, Liu S-Q, Pilone GJ. 2001. Growth and arginine metabolism of the wine lactic acid bacteria Lactobacillus buchneri and Oenococcus oeni at different pH values and arginine concentrations. Appl Environ Microb (Aem) 67(4):1657-62.
42. Deibel R. 1964. Utilization of arginine as an energy source for the growth of Streptococcus faecalis. J Bacteriol 87(5):988-92.
43. Dennis M, Howarth N, Key P, Pointer M, Massey R. 1989. Investigation of ethyl carbamate levels in some fermented foods and alcoholic beverages. Food Addit Contam 6(3):383-9.
44. Dennis M, Howarth N, Massey R, Parker I, Scotter M, Startin J. 1986. Method for the analysis of ethyl carbamate in alcoholic beverages by capillary gas chromatography. J Chromatogr A 369:193-8.
45. Dürr M, Urech K, Boller T, Wiemken A, Schwencke J, Nagy M. 1979. Sequestration of arginine by polyphosphate in vacuoles of yeast (Saccharomyces cerevisiae). Arch Microbiol 121(2):169-75.
46. Esti M, Fidaleo M, Moresi M, Tamborra P. 2007. Modeling of urea degradation in white and rose wines by acid urease. J Agric Food Chem 55(7):2590-6.
47. Famuyiwa OO, Ough C. 1991. Modification of acid urease activity by fluoride ions and malic acid in wines. Am J Enol Viticult 42(1):79-80.
48. Fauhl C, Catsburg R, Wittkowski R. 1993. Determination of ethyl carbamate in soy sauces. Food Chem 48(3):313-6.
49. Fidaleo M, Esti M, Moresi M. 2006. Assessment of urea degradation rate in model wine solutions by acid urease from Lactobacillus fermentum. J Agric Food Chem 54(17):6226-35.
50. Forkert P-G, Lee RP. 1997. Metabolism of ethyl carbamate by pulmonary cytochrome P450 and carboxylesterase isozymes: involvement of CYP2E1 and hydrolase A. Toxicol Appl Pharm 146(2):245-54.
51. Fu ML, Liu J, Chen QH, Liu XJ, He GQ, Chen JC. 2010. Determination of ethyl carbamate in Chinese yellow rice wine using high-performance liquid chromatography with fluorescence detection. Intl J Food Sci Technol 45(6):1297-302.
52. Fujinawa S, Burns G, De La Teja P. 1990a. Application of acid urease to reduction of urea in commercial wines. Am J Enol Viticult 41(4):350-4.
53. Fujinawa S, Kodama S, Todoroki H, Suzuki T. 1992. Trace urea determination in red wine and its degradation rate by acid urease. Am J Enol Viticult 43(4):362-6.
54. Fujinawa S, Todoroki H, Ohashi N, Toda J, Terasaki M. 1990b. Application of an acid urease to wine: determination of trace urea in wine. J Food Sci 55(4):1018-22.
55. Funch F, Lisbjerg S. 1988. Analysis of ethyl carbamate in alcoholic beverages. Zeitschrift für Lebensmittel-Untersuchung und Forschung 186(1):29-32.
56. Genbauffe F, Cooper T. 1986. Induction and repression of the urea amidolyase gene in Saccharomyces cerevisiae. Mol Cell Biol 6(11):3954-64.
57. Granchi L, Paperi R, Rosellini D, Vincenzini M. 1998. Strain variation of arginine catabolism among malolactic Oenococcus oeni strains of wine origin. Ital J Food Sci 10(4):351-7.
58. Grenson M. 1966. Multiplicity of the amino acid permeases in Saccharomyces cerevisiae: II. Evidence for a specific lysine-transporting system. BBA-Gen Subjects 127(2):339-46.
59. Grenson M. 1983a. Inactivation-reactivation process and repression of permease formation regulate several ammonia-sensitive permeases in the yeast Saccharomyces cerevisiae. Eur J Biochem 133(1):135-9.
60. Grenson M. 1983b. Study of the positive control of the general amino-acid permease and other ammonia-sensitive uptake systems by the product of the NPR1 gene in the yeast Saccharomyces cerevisiae. Eur J Biochem 133(1):141-4.
61. Grenson M, Crabeel M, Wiame J, Bechet J. 1968. Inhibition of protein synthesis and simulation of permease turnover in yeast. Biochem Bioph Res Commun 30(4):414-9.
62. Grenson M, Hennaut C. 1971. Mutation affecting activity of several distinct amino acid transport systems in Saccharomyces cerevisiae. J Bacteriol 105(2):477-82.
63. Grenson M, Hou C, Crabeel M. 1970. Multiplicity of the amino acid permeases in Saccharomyces cerevisiae IV. Evidence for a general amino acid permease. J Bacteriol 103(3):770-7.
64. Grenson M, Mousset M, Wiame J, Bechet J. 1966. Multiplicity of the amino acid permeases in Saccharomyces cerevisiae: I. Evidence for a specific arginine-transporting system. BBA-Gen Subjects 127(2):325-38.
65. Guengerich FP, Kim DH. 1991. Enzymic oxidation of ethyl carbamate to vinyl carbamate and its role as an intermediate in the formation of 1, N6-ethenoadenosine. Chem Res Toxicol 4(4):413-21.
66. Guengerich FP, Kim DH, Iwasaki M. 1991. Role of human cytochrome P-450 IIE1 in the oxidation of many low-molecular-weight cancer suspects. Chem Res Toxicol 4(2):168-79.
67. Ha M-S, Hu S-J, Hee R-p, Lee H, Kwon K-S, Han E-M, Kim K-M, Ko E-J, Ha S-D, Bae D-H. 2006a. Estimation of Korean adult's daily intake of ethyl carbamate through Korean commercial alcoholic beverages based on the monitoring. Food Sci Biotechnol 15(1):112-6.
68. Ha M-S, Kwon K-S, Kim M, Hee R-p, Hu S-J, Lee H, Kim K-M, Ko E-J, Ha S-D, Bae D-H. 2006b. Exposure assessment of ethyl carbamate in alcoholic beverages. J Microbiol Biotechnol 16(3):480-3.
69. Hashiguchi T, Horii S, Izu H, Sudo S. 2010. The concentration of ethyl carbamate in commercial ume (Prunus mume) liqueur products and a method of reducing it. Biosci Biotechnol Biochem (BBB) 74(10):2060-6.
70. Hasnip S, Caputi A, Crews C, Brereton P. 2004. Effects of storage time and temperature on the concentration of ethyl carbamate and its precursors in wine. Food Addit Contam 21(12):1155-61.
71. Hasnip S, Crews C, Potter N, Christy J, Chan D, Bondu T, Matthews W, Walters B, Patel K. 2007. Survey of ethyl carbamate in fermented foods sold in the United Kingdom in 2004. J Agric Food Chem 55(7):2755-9.
72. Henschke PA, Jiranek V. 1991. Hydrogen sulfide formation during fermentation: effect of nitrogen composition in model grape must. In: Davis CA, editor. Proceedings of the International Symposium on Nitrogen in Grapes and Wine. Seattle, Washington: American Society for Enology and Viticulture Publishing. p 172-84.
73. Herbert N. 1985. Nitrogen catabolite repression in yeasts and filamentous fungi. Adv Microbial Physiol 26:1-88.
74. Herbert P, Santos L, Bastos M, Barros P, Alves A. 2002. New HPLC method to determine ethyl carbamate in alcoholic beverages using fluorescence detection. J Food Sci 67(5):1616-20.
75. Horii S, Goto K. 2010. Determination of ethyl carbamate in sake using headspace solid-phase microextraction. J Inst Brew 116(2):177-81.
76. Horwitz W. 1995. Official methods of analysis of AOAC International. Association of Official Analytical Chemists. Washington: AOAC.
77. Jagerdeo E, Dugar S, Foster GD, Schenck H. 2002. Analysis of ethyl carbamate in wines using solid-phase extraction and multidimensional gas chromatography/mass spectrometry. J Agric Food Chem 50(21):5797-802.
78. Jaryj E, Lorenz K, Spangenberg B. 2008. A simple method for the quantification of urethane in spirits. J Liquid Chromatogr Related Technol 31(13):1969-76.
79. Jauniaux JC, Urrestarazu LA, Wiame J. 1978. Arginine metabolism in Saccharomyces cerevisiae: subcellular localization of the enzymes. J Bacteriol 133(3):1096-107.
80. Jonsson S, Clausen E, Raa J. 1983. Amino acid degradation by a Lactobacillus plantarum strain from fish. Syst Appl Microbiol 4(1):148-54.
81. Kakimoto S, Miyashita H, Sumino Y, Akiyama SI. 1990a. Properties of acid ureases from Lactobacillus and Streptococcus strains. Agric Biol Chem 54(2):381-6.
82. Kakimoto S, Sumino Y, Akiyama SI, Nakao Y. 1989. Purification and characterization of acid urease from Lactobacillus reuteri. Agric Biol Chem 53(4):1119-25.
83. Kakimoto S, Sumino Y, Kawahara K, Yamazaki E, Nakatsui I. 1990b. Purification and characterization of acid urease from Lactobacillus fermentum. Appl Microbiol Biotechnol 32(5):538-43.
84. Kim D, Lee T, Noh B, Lee D, Kim E. 1995. Application of acid urease to prevent ethyl carbamate formation in takju processing. Foods Biotechnol 17:469-75.
85. Kitamoto K, Oda K, Gomi K, Takahashi K. 1991. Genetic engineering of a sake yeast producing no urea by successive disruption of arginase gene. Appl Environ Microb (Aem) 57(1):301-6.
86. Kodama S, Yotsuzuka F. 1996. Acid urease: reduction of ethyl carbamate formation in sherry under simulated baking conditions. J Food Sci 61(2):304-7.
87. Konings W, Poolman B, Driessen A, Maloney PC. 1989. Bioenergetics and solute transport in Lactococci. Crit Rev Microbiol 16(6):419-76.
88. Kuensch U, Temperli A, Mayer K. 1974. Conversion of arginine to ornithine during malo-lactic fermentation in red Swiss wine. Am J Enol Viticult 25(4):191-3.
89. Lachenmeier D, Lima M, Nóbrega I, Pereira J, Kerr-Corrêa F, Kanteres F, Rehm J. 2010. Cancer risk assessment of ethyl carbamate in alcoholic beverages from Brazil with special consideration to the spirits cachaça and tiquira. BMC Cancer 10(1):266.
90. Lachenmeier DW. 2005. Rapid screening for ethyl carbamate in stone-fruit spirits using FTIR spectroscopy and chemometrics. Anal Bioanal Chem 382(6):1407-12.
91. Lachenmeier DW, Frank W, Kuballa T. 2005a. Application of tandem mass spectrometry combined with gas chromatography to the routine analysis of ethyl carbamate in stone-fruit spirits. Rapid Commun Mass Spectrom 19(2):108-12.
92. Lachenmeier DW, Kanteres F, Kuballa T, López MG, Rehm J. 2009. Ethyl carbamate in alcoholic beverages from Mexico (tequila, mezcal, bacanora, sotol) and Guatemala (cuxa): market survey and risk assessment. Intl J Environ Res Public Health 6(1):349-60.
93. Lachenmeier DW, Nerlich U, Kuballa T. 2006. Automated determination of ethyl carbamate in stone-fruit spirits using headspace solid-phase microextraction and gas chromatography-tandem mass spectrometry. J Chromatogr A 1108(1):116-20.
94. Lachenmeier DW, Schehl B, Kuballa T, Frank W, Senn T. 2005b. Retrospective trends and current status of ethyl carbamate in German stone-fruit spirits. Food Addit Contam 22(5):397-405.
95. Lafuente L, Fabre S. 2000. Stone fruit spirits: reduction of the ethyl carbamate content. Revue des Oenologues et des Techniques Vitivinicoles et Oenologiques 96:27-30.
96. Latt SA. 1974. Sister chromatid exchanges, indices of human chromosome damage and repair: detection by fluorescence and induction by mitomycin C. Proc Natl Acad Sci USA 71(8):3162-6.
97. LCBO (Liquor Control Board of Ontario). 2006. Information supplied by the Liquor Control Board of Ontario. LCBO Corporate Communications, 55 Lake Shore Boulevard, East Toronto, ONM5E 1A4.
98. Le Kim YK, Koh E, Chung HJ, Kwon H. 2000. Determination of ethyl carbamate in some fermented Korean foods and beverages. Food Addit Contam 17(6):469-75.
99. Liu J, Xu Y, Nie Y, Zhao GA. 2012. Optimization production of acid urease by Enterobacter sp. in an approach to reduce urea in Chinese rice wine. Bioprocess Biosyst Eng 35(4):651-7.
100. Liu S, Davis C, Brooks J. 1995b. Growth and metabolism of selected lactic acid bacteria in synthetic wine. Am J Enol Viticult 46(2):166-74.
101. Liu S, Pritchard G, Hardman M, Pilone G. 1995a. Occurrence of arginine deiminase pathway enzymes in arginine catabolism by wine lactic acid bacteria. Appl Environ Microbiol 61(1):310-6.
102. Liu SQ, Pilone G. 1998. A review: arginine metabolism in wine lactic acid bacteria and its practical significance. J Appl Microbiol 84(3):315-27.
103. Liu SQ, Pritchard G, Hardman M, Pilone G. 1994. Citrulline production and ethyl carbamate (urethane) precursor formation from arginine degradation by wine lactic acid bacteria Leuconostoc oenos and Lactobacillus buchneri. Am J Enol Viticult 45(2):235-42.
104. Liu SQ, Pritchard G, Hardman M, Pilone G. 1996. Arginine catabolism in wine lactic acid bacteria: is it via the arginine deiminase pathway or the arginase-urease pathway? J Appl Microbiol 81(5):486-92.
105. Liu Y, Dong B, Qin Z, Yang N, Lu Y, Yang L, Chang F, Wu Y. 2011. Ethyl carbamate levels in wine and spirits from markets in Hebei Province, China. Food Addit Contam 4(1):1-5.
106. Löhnertz O, Prior B, Bleser M, Linsenmeier A. 2000. Influence of N-supply and soil management on the nitrogen composition of grapes. Proceedings of XXV International Horticultural Congress, Part 2: Mineral Nutrition and Grape and Wine Quality; Brussels, Belgium, 2-7 August 1998.
107. Lu D, Wang G, Xiong L, Wen Y. 2009. Rapid determination of ethyl carbamate in alcoholic beverages with GC/MS coupling with supported liquid-liquid extration. J Chin Mass Spectrom Soc 30:145-8.
108. Ma YP, Deng FQ, Chen DZ, Sun SW. 1995. Determination of ethyl carbamate in alcoholic beverages by capillary multi-dimensional gas chromatography with thermionic specific detection. J Chromatogr A 695(2):259-65.
109. Madrera RR, Valles BS. 2009. Determination of ethyl carbamate in cider spirits by HPLC-FLD. Food Control 20(2):139-43.
110. Magasanik B. 1992. Regulation of nitrogen utilization. In: Jones EW, Pringle JR, Broach JR, editors. The molecular and cell biology of the yeast Saccharomyces cerevisiae: gene expression. N.Y.: Cold Spring Harbor Laboratory Publishing. p 283-317.
111. Manca De Nadra MC, Pesce de Ruiz Holgado AA, Oliver G. 1988. Arginine dihydrolase pathway in Lactobacillus buchneri: a review. Biochimie 70(3):367-74.
112. Matile P, Wiemken A. 1967. The vacuole as the lysosome of the yeast cell. Arch Mikrobiol 56(2):148-55.
113. Messenguy F, Dubois E. 2000. Regulation of arginine metabolism in Saccharomyces cerevisiae: a network of specific and pleiotropic proteins in response to multiple environmental signals. Food Sci Biotechnol 38(4):277-85.
114. Messenguy F, Penninckx M, Wiame JM. 1971. Interaction between arginase and ornithine carbamoyltransferase in Saccharomyces cerevisiae. Eur J Biochem 22(2):277-86.
115. Messenguy F, Wiame JM. 1969. The control of ornithinetranscarbamylase activity by arginase in Saccharomyces cerevisiae. FEBS Lett 3(1):47-9.
116. Middelhoven W. 1964. The pathway of arginine breakdown in Saccharomyces cerevisiae. Bba-Gen Subjects 93(3):650-2.
117. Middelhoven W. 1968. The derepression of arginase and of ornithine transaminase in nitrogen-starved baker's yeast. Bba-Gen Subjects 156(2):440-3.
118. Middelhoven W. 1970. Induction and repression of arginase and ornithine transaminase in baker's yeast. Antonie Van Leeuwenhoek Intl J 36(1):1-19.
119. Mildau G, Preuß A, Frank W, Heering W. 1987. Ethylcarbamat (Urethan) in alkoholischen Getränken: verbesserte analyse und lichtabhängige bildung. Dtsch Lebensm Rundsch 83:69-74.
120. Miller JA, Miller EC. 1983. The metabolic activation and nucleic acid adducts of naturally-occurring carcinogens: recent results with ethyl carbamate and the spice flavors safrole and estragole. Brit J Cancer 48(1):1-15.
121. Mills DA, Rawsthorne H, Parker C, Tamir D, Makarova K. 2005. Genomic analysis of Oenococcus oeni PSU-1 and its relevance to winemaking. FEMS Microbiol Rev 29(3):465-75.
122. Mira de Orduña R, Liu SQ, Patchett M, Pilone G. 2000. Ethyl carbamate precursor citrulline formation from arginine degradation by malolactic wine lactic acid bacteria. FEMS Microbiol Lett 183(1):31-5.
123. Mirvish SS. 1968. The carcinogenic action and metabolism of urethan and N-hydroxyurethan. Adv Cancer Res 11:1-42.
124. Miyagawa K, Sumida M, Nakao M, Harada M, Yamamoto H, Kusumi T, Yoshizawa K, Amachi T, Nakayama T. 1999. Purification, characterization, and application of an acid urease from Arthrobacter mobilis. J Biotechnol 68(2):227-36.
125. Monteiro FF, Bisson LF. 1991. Amino acid utilization and urea formation during vinification fermentations. Am J Enol Viticult 42(3):199-208.
126. Morita H, Toh H, Fukuda S, Horikawa H, Oshima K, Suzuki T, Murakami M, Hisamatsu S, Kato Y, Takizawa T. 2008. Comparative genome analysis of Lactobacillus reuteri and Lactobacillus fermentum reveal a genomic island for reuterin and cobalamin production. DNA Res 15(3):151-61.
127. Nomeir A, Ioannou Y, Sanders J, Matthews H. 1989. Comparative metabolism and disposition of ethyl carbamate (urethane) in male Fischer 344 rats and male B6C3F1 mice. Toxicol Appl Pharm 97(2):203-15.
128. Office Internationale de la Vigne & du Vin. 1990. Recueil des Mè thodes Internationales D́analyse des Vins. Paris: OIV.
129. Ohsumi Y, Anraku Y. 1981. Active transport of basic amino acids driven by a proton motive force in vacuolar membrane vesicles of Saccharomyces cerevisiae. J Biol Chem 256(5):2079-82.
130. Ough C. 1991. Influence of nitrogen compounds in grapes on ethyl carbamate formation in wines. In: American Society for Enology and Viticulture, editor. Proceedings of the International Symposium on Nitrogen in Grapes and Wine. Seattle, Washington: Washington Publishing. p 165-71.
131. Ough C, Stevens D, Sendovski T, Huang Z, An D. 1990. Factors contributing to urea formation in commercially fermented wines. Am J Enol Viticult 41(1):68-73.
132. Ough C, Trioli G. 1988. Urea removal from wine by an acid urease. Am J Enol Viticult 39(4):303-7.
133. Ough CS. 1976. Ethyl carbamate in fermented beverages and foods. I. Naturally occurring ethylcarbamate. J Agric Food Chem 24(2):323-8.
134. Pandey V. 1980. Interdependence of glucose and arginine catabolism in Streptococcus faecalis R. ATCC 8043. Biochem Biophys Res Commun 96(4):1480-7.
135. Park HD, Shin MC, Woo IS. 2001. Antisense-mediated inhibition of arginase (CAR1) gene expression in Saccharomyces cerevisiae. J Biosci Bioeng 92(5):481-4.
136. Park KK, Liem A, Stewart BC, Miller JA. 1993. Vinyl carbamate epoxide, a major strong electrophilic, mutagenic and carcinogenic metabolite of vinyl carbamate and ethyl carbamate (urethane). Carcinogenesis 14(3):441-50.
137. Patrignani F, Ndagijimana M, Belletti N, Gardini F, Vernocchi P, Lanciotti R. 2012. Biogenic amines and ethyl carbamate in primitivo wine: survey of their concentrations in commercial products and relationship with the use of malolactic starter. J Food Protect 75(3):591-6.
138. Penninckx M, Wiame J-M. 1976. Affinity of arginase for ornithine carbamoyltransferase in Saccharomyces cerevisiae. J Mol Biol 104(4):819-31.
139. Perestrelo R, Petronilho S, Câmara JS, Rocha SM. 2010. Comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry combined with solid-phase microextraction as a powerful tool for quantification of ethyl carbamate in fortified wines. The case study of Madeira wine. J Chromatogr A 1217(20):3441-5.
140. Plutowska B, Wardencki W. 2007. Aromagrams-aromatic profiles in the appreciation of food quality. Food Chem 101(2):845-72.
141. Polychroniadou E, Kanellaki M, Iconomopoulou M, Koutinas A, Marchant R, Banat I. 2003. Grape and apple wines volatile fermentation products and possible relation to spoilage. Bioresour Technol 87(3):337-9.
142. Poolman B, Driessen A, Konings W. 1987a. Regulation of arginine-ornithine exchange and the arginine deiminase pathway in Streptococcus lactis. J Bacteriol 169(12):5597-604.
143. Poolman B, Driessen A, Konings WN. 1987b. Regulation of solute transport in streptococci by external and internal pH values. Microbiol Rev 51(4):498-508.
144. Ramos F, Thuriaux P, Wiame J, Bechet J. 1970. The participation of ornithine and citrulline in the regulation of arginine metabolism in Saccharomyces cerevisiae. Eur J Biochem 12(1):40-7.
145. Roberts GT, Allen JW. 1980. Tissue-specific induction of sister chromatid exchanges by ethyl carbamate in mice. Environ Mol Mutagen 2(1):17-26.
146. Romero SV, Reguant C, Bordons A, Masqué MC. 2009. Potential formation of ethyl carbamate in simulated wine inoculated with Oenococcus oeni and Lactobacillus plantarum. Intl J Food Sci Technol 44(6):1206-13.
147. Russell JB, Cook GM. 1995. Energetics of bacterial growth: balance of anabolic and catabolic reactions. Microbiol Rev 59(1):48-62.
148. Sakano K, Oikawa S, Hiraku Y, Kawanishi S. 2002. Metabolism of carcinogenic urethane to nitric oxide is involved in oxidative DNA damage. Free Radical Biol Med 33(5):703-14.
149. Salaman M, Roe F. 1953. Incomplete carcinogens: ethyl carbamate (urethane) as an initiator of skin tumour formation in the mouse. Br J Cancer 7(4):472-81.
150. Salmon AG, Zeise L. 1991. Risks of carcinogenesis from urethane exposure. Florida: CRC Press. p 115
151. Sato T, Ohsumi Y, Anraku Y. 1984. An arginine/histidine exchange transport system in vacuolar-membrane vesicles of Saccharomyces cerevisiae. J Biol Chem 259(18):11509-11.
152. Schehl B, Senn T, Lachenmeier DW, Rodicio R, Heinisch JJ. 2007. Contribution of the fermenting yeast strain to ethyl carbamate generation in stone fruit spirits. Appl Microbiol Biotechnol 74(4):843-50.
153. Selvamurugan C, Lavanya A, Sivasankar B. 2007. A comparative study on immobilization of urease on different matrices. J Sci Ind Res India 66(8):655-9.
154. Sen N, Seaman S, Weber D. 1992. A method for the determination of methyl carbamate and ethyl carbamate in wines. Food Addit Contam 9(2):149-60.
155. Shimkin MB, Stoner GD. 1975. Lung tumors in mice: application to carcinogenesis bioassay. Adv Cancer Res 21:1-58.
156. Skipper HE, Bennett LL, Bryan CE, White L, Newton MA, Simpson L. 1951. Carbamates in the chemotherapy of leukemia VIII. Over-all tracer studies on carbonyl-labeled urethan, methylene-labeled urethan, and methylene-labeled ethyl alcohol. Cancer Res 11(1):46-51.
157. Sponholz W. 1992. The breakdown of arginine by lactic acid bacteria and its relation to ethylcarbamate production. Biol Oggi 6:15-24.
158. Steinkraus K. 2002. Fermentations in world food processing. Compr Rev Food Sci Food Saf 1(1):23-32.
159. Strathern JN, Jones EW, Broach JR. 1982. The molecular biology of the yeast Saccharomyces: metabolism and gene expression. N.Y.: Cold Spring Harbor Laboratory Publishing.
160. Subramanian K, Weiss RL, Davis RH. 1973. Use of external, biosynthetic, and organellar arginine by Neurospora. J Bacteriol 115(1):284-90.
161. Suizu T, Iimura Y, Gomi K, Takahashi K, Hara S, Yoshizawa K, Tamura G. 1990. Construction of urea non-producing yeast Saccharomyces cerevisiae by disruption of the car1 gene. Agric Biol Chem 54(2):537-9.
162. Sumrada R, Cooper TG. 1978. Control of vacuole permeability and protein degradation by the cell cycle arrest signal in Saccharomyces cerevisiae. J Bacteriol 136(1):234-46.
163. Sumrada R, Gorski M, Cooper T. 1976. Urea transport-defective strains of Saccharomyces cerevisiae. J Bacteriol 125(3):1048-56.
164. Suzuki K, Benno Y, Mitsuoka T, Takebe S, Kobashi K, Hase J. 1979. Urease-producing species of intestinal anaerobes and their activities. Appl Environ Microb (Aem) 37(3):379-82.
165. Takebe S, Kobashi K. 1988. Acid urease from Lactobacillus of rat intestine. Chem Pharm Bull 36(2):693-9.
166. Tannenbaum A. 1964. Contribution of urethan studies to the understanding of carcinogenesis. Natl Cancer Inst Monogr 14:341-56.
167. Tempest D, Neijssel O. 1992. Physiological and energetic aspects of bacterial metabolite overproduction. FEMS Microbiol Lett 100(1):169-76.
168. Thibon C, Marullo P, Claisse O, Cullin C, Dubourdieu D, Tominaga T. 2008. Nitrogen catabolic repression controls the release of volatile thiols by Saccharomyces cerevisiae during wine fermentation. Fems Yeast Res 8(7):1076-86.
169. Thompson J, Harr RJ, Donkersloot JA. 1990. N5-(l-1-Carboxyethyl)-l-ornithine: NADP +oxidoreductase in Streptococcus lactis: distribution, constitutivity, and regulation. Curr Microbiol 20(4):239-44.
170. Thorgeirsson UP, Dalgard DW, Reeves J, Adamson RH. 1994. Tumor incidence in a chemical carcinogenesis study of nonhuman primates. Regul Toxicol Pharm 19(2):130-51.
171. Trioli G, Ough C. 1989. Causes for inhibition of an acid urease from Lactobacillus fermentus. Am J Enol Viticult 40(4):245-52.
172. US Food and Drug Administration. 1997. Ethyl carbamate preventative action manual. center for food safety and applied nutrition. Available from: http://www.fda.gov/downloads/food/foodborneillnesscontaminants/ucm119802.pdf. Accessed 2004.
173. Uthurry C, Lepe J, Lombardero J, Garcia Del Hierro J. 2006. Ethyl carbamate production by selected yeasts and lactic acid bacteria in red wine. Food Chem 94(2):262-70.
174. Vahl M. 1993. A survey of ethyl carbamate in beverages, bread and acidified milks sold in Denmark. Food Addit Contam 10(5):585-92.
175. Vissers S, Urrestarazu LA, Jauniaux JC, Wiame JM. 1982. Inhibition of ornithine carbamoyltransferase by arginase among yeasts: correlation with energy production, subcellular localization and enzyme synthesis. Microbiology 128(6):1235-47.
176. Vrancken G, Rimaux T, Weckx S, De Vuyst L, Leroy F. 2009. Environmental pH determines citrulline and ornithine release through the arginine deiminase pathway in Lactobacillus fermentum IMDO 130101. Intl J Food Microbiol 135(3):216-22.
177. Walker G, Winterlin W, Fouda H, Seiber J. 1974. Gas chromatographic analysis of urethane (ethyl carbamate) in wine. J Agric Food Chem 22(6):944-7.
178. Weiss RL. 1973. Intracellular localization of ornithine and arginine pools in Neurospora. J Biol Chem 248(15):5409-13.
179. Whitney P, Cooper T. 1972. Urea carboxylase and allophanate hydrolase two components of adenosine triphosphate: urea amido-lyase in Saccharomyces cerevisiae. J Biol Chem 247(5):1349-53.
180. Whiton R, Zoecklein B. 2002. Determination of ethyl carbamate in wine by solid-phase microextraction and gas chromatography/mass spectrometry. Am J Enol Viticult 53(1):60-3.
181. Wiame J. 1974. Evolving of arginase-ornithine carbamoyltransferase interaction. Proceedings of the 9th FEBS Meeting 1974. Budapest: Publishing House of the Hungarian Academy of Sciences.
182. Wibowo D, Eschenbruch R, Davis C, Fleet G, Lee T. 1985. Occurrence and growth of lactic acid bacteria in wine: a review. Am J Enol Viticult 36(4):302-13.
183. Wiemken A, Nurse P. 1973. Isolation and characterization of the amino-acid pools located within the cytoplasm and vacuoles of Candida utilis. Planta 109(4):293-306.
184. Wiemken A, Schellenberg M, Urech K. 1979. Vacuoles: the sole compartments of digestive enzymes in yeast (Saccharomyces cerevisiae)? Arch Microbiol 123(1):23-35.
185. Woo I, Kim I, Yun U, Chung S, Rhee I, Choi S, Park H. 2001. An improved method for determination of ethyl carbamate in Korean traditional rice wine. J Ind Microbiol Biotechnol 26(6):363-8.
186. Wu P, Pan X, Wang L, Shen X, Yang D. 2012. A survey of ethyl carbamate in fermented foods and beverages from Zhejiang, China. Food Control 23(1):286-8.
187. Yamazaki E, Kurasawa T, Kakimoto S, Sumino Y, Nakatstui I. 1990. Characteristics of acid urease from Streptococcus mitior. Agric Biol Chem 54(9):2433-5.
188. Yoshiuchi K, Watanabe M, Nishimura A. 2000. Breeding of a non-urea-producing sake yeast with killer character using a kar1-1 mutant as a killer donor. J Ind Microbiol Biotechnol 24(3):203-9.
189. Zhang Y, Ren Y, Zhang Y. 2009. New research developments on acrylamide: analytical chemistry, formation mechanism, and mitigation recipes. Chem Rev 109(9):4375-97.
190. Zhang Y, Zhang J. 2008. Optimization of headspace solid-phase microextraction for analysis of ethyl carbamate in alcoholic beverages using a face-centered cube central composite design. Anal Chim Acta 627(2):212-8.
191. Zhao X, Du G, Zou H, Fu J, Zhou J, Chen J. 2013a. Progress in preventing the accumulation of ethyl carbamate in alcoholic beverages. Trends Food Sci Technol 32(2):97-107.
192. Zhao X, Zou H, Fu J, Chen J, Zhou J, Du G. 2013b. Nitrogen regulation involved in the accumulation of urea in Saccharomyces cerevisiae. Yeast 30(11): 437-47.
193. Zhou J, Chen S, Wang J. 2008. Research on orientedly immobilized urease via concanavalin A. Chin J Biotechnol 24(4):617-21.
194. Zimmerli B, Baumann U, Nägeli P, Battaglia R. 1986. Occurrence and formation of ethylcarbamate (urethane) in fermented foods. Some preliminary results. Proceedings of Euro Food Tox II, Zürich. p 243.
195. Zimmerli B, Schlatter J. 1991. Ethyl carbamate: analytical methodology, occurrence, formation, biological activity and risk assessment. Mutat Res-Genet Toxicol Environ 259(3):325-50.
196. Zotta T, Ricciardi A, Rossano R, Parente E. 2008. Urease production by Streptococcus thermophilus. Food Microbiol 25(1):113-9.