Ethyl Carbamate in Alcoholic Beverages and Fermented Foods - ACS

Chapter 34

Ethyl Carbamate in Alcoholic Beverages and Fermented Foods

Downloaded by RUTGERS UNIV on March 16, 2016 | http://pubs.acs.org Publication Date: February 14, 1992 | doi: 10.1021/bk-1992-0484.ch034

Gregory W. Diachenko, Benjamin J. Canas, Frank L. Joe, and Michael DiNovi Division of Food Chemistry and Technology, U.S. Food and Drug Administration, 200 C Street, SW, Washington, DC 20204

Significant research and regulatory activity have been focused on ethyl carbamate (EC) as a result of Canada's establishment of regulatory limits for E C in alcoholic beverages. Industry, academic, and government laboratories have developed analytical methods for E C and confirmed its presence in a wide variety of alcoholic beverages. Although E C is an animal carcinogen, insufficient toxicological data are available for a meaningful human risk assessment. The Food and Drug Administration has requested additional toxicological studies and established voluntary E C reduction programs with the United States wine and distilled spirits industries. These programs aim at identifying factors contributing to E C formation and reducing E C to the lowest levels that are technologically feasible. This chapter presents recent industry and government data on E C levels in alcoholic beverages and fermented foods and an initial assessment of E C intake from these sources. Results of studies conducted by industry as part of their voluntary E C reduction programs are also presented. Since December 1985, when Canada announced regulatory limits for ethyl carbamate (EC) in alcoholic beverages, considerable research and regulatory activity have been focused on this compound. The reported presence of E C in alcoholic beverages was of immediate food safety concern because it is a well-known animal carcinogen. Following the Canadian findings and regulatory action, the U.S. Food and Drug Administration (FDA) initiated a wide range of activities. These activities included a limited survey of alcoholic beverages, evaluation of E C toxicity data, assessment of other sources of E C exposure, and most important, working with industry to reduce E C levels. The current status of the toxicological evaluation can be addressed by noting the conclusion of the Cancer Assessment Committee of F D A ' s Center for Food Safety and Applied Nutrition, which stated, "... that the data were not sufficient to perform a meaningful assessment of the risk posed by urethane in alcoholic beverages..." (/). At F D A ' s request, the National Toxicology Program (NTP) has initiated toxicological This chapter not subject to U.S. copyright Published 1992 American Chemical Society Finley et al.; Food Safety Assessment ACS Symposium Series; American Chemical Society: Washington, DC, 1992.


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research to provide the data needed for a quantitative estimate of the risk due to E C in alcoholic beverages. While awaiting the results of NTP* s toxicological studies, F D A has addressed the exposure side of the risk assessment equation. The remainder of this paper will focus on providing an overview of the efforts of F D A and industry to determine E C concentrations, total E C exposure, and ways to reduce E C in alcoholic beverages to the lowest level that is technologically feasible. F D A and the Bureau of Alcohol, Tobacco, and Firearms (B ATF) initially surveyed domestic and imported alcoholic beverages for E C to confirm the Canadian reports and assess the frequency and levels of EC's occurrence. Table 1 summarizes the findings of E C in a wide range of beverages collected from January 1986 through August 1987 (2). The average levels for various product classes varied dramatically, with fruit brandy, bourbon whiskey, sherry, and sake having the highest values. These higher-level product classes also included the greatest percentages of samples that exceeded the following Canadian E C regulatory limits: 150 ppb in distilled spirits; 100 ppb in dessert wines (>14% alcohol, e.g., port and sherry); 30 ppb in table wines (< 14% alcohol); 400 ppb in fruit brandy and liqueur; and 200 ppb in sake. The U.S. data were consistent with the Canadian findings (3) and suggested the need to reduce E C levels and generate the toxicological and exposure data necessary for F D A to evaluate the risk posed by EC. To enable a more complete assessment of the total human exposure to E C , F D A (4,5) developed analytical methods and analyzed a wide variety of fermented foods. The selected foods included many that had previously been reported by Ough (6) to contain low concentrations of EC. Canas et al. (4,5) analyzed a greater number and variety of fermented foods, and their results are summarized in Tables 2 and 3. Average levels of E C were generally 25 ppb E C and no more than 1% of the volume of dessert wine would contain >90 ppb (7). Although these targets are below the Canadian regulatory limits, the commitment was also made to conduct an annual survey, and if possible, accelerate the target date or modify the goals to reduce E C levels to the greatest extent possible. To move toward attaining these goals, the wine industry supported extensive research on the mechanism of E C formation and also investigated practical measures to reduce E C levels. Ough (13) demonstrated that urea, citrulline, and carbamyl phosphate could all react with ethanol to produce EC. Several other precursors for E C formation were also investigated, and after thorough testing Ough concluded that urea, a natural by-product of yeast metabolism, is the main precursor of E C in wines (74). He also demonstrated that arginine was the major amino acid metabolized by yeast to produce urea. Any urea that is not utilized by the yeast during fermentation can then react with ethanol over time to form E C . If the juice or musk originally contained high levels of nitrogenous compounds that are metabolized by yeast before urea, more urea would remain after fermentation to form higher E C concentrations. Ough (13) also demonstrated that citrulline, another amino acid found in various grapes, is a precursor of E C in wines, although not to as great an extent as urea. Based on these research findings, the wine industry made the following recom mendations to all U.S. wineries concerning ways to minimize development of E C in wines (75; Wine Institute, personal communication, 1989): (1) encourage grape growers to minimize fertilization of vineyards, as research indicates that heavily fertilized vineyards tend to contain relatively high levels of arginine and other nitrogenous compounds; (2) analyze grapes from heavily fertilized vineyards for total α-amino acids, as research suggests that grapes exceeding 1500 ppm may develop significant E C potentials during fermentation; (3) if possible, use prise de mousse yeast to produce wine with lower levels of urea and EC, especially if the juice has high levels of total α-amino acids; and (4) fortify dessert wines at the point in fermentation when urea levels are lowest, as E C potentials are significantly affected by the urea levels at the time the fermentation is halted by fortification. A more recent E C reduction process has also been developed that recommends the addition of urease, an enzyme that removes the unmetabolized urea, to wines which contain higher postfermentation urea levels (Wine Institute, personal communication, 1989). As these recommendations for reducing E C are instituted, it is expected that average E C levels and the percentage of commercial wines with higher E C concentrations will be lowered. In 1989 the wine industry conducted its initial E C survey to establish a baseline for measuring future progress. The results of this survey are summarized in Table 6 (76). The 5 ppb mean and volume-weighted average values for the 193 samples of bottled table wines (14% alcohol were also below their 1989

Finley et al.; Food Safety Assessment ACS Symposium Series; American Chemical Society: Washington, DC, 1992.

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Table 6. Summary of 1989 Wine Industry Ethyl Carbamate Survey

Wine Class 14% alcohol

Ethyl Carbamate (ppb) Weighted % Exceeding Mean Averaged Goaf

a

Range

193

1-24

5

5

0

37

1-862

80

33

24

N

:

SOURGE Unpublshed data provided by the Wine Institute (76). N = number of samples. ^Weighted Average represents the average level computed by the Wine Institute using a weighting factor that takes into account the market share or production volume represented by each winery. Percentage of survey samples that exceeded the wine industry target goals for the 1995 harvest, which are that no more than 1 % of the volume of table wine (< 14% alcohol) would be above 2 5 ppb and no moc than 1 % of the volume of dessert wine (>14% alcohol) would be above 9 0 ppb (7). a



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Ethyl Carbamate in Alcohol and Foods

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target of 60 ppb on a volume-weighted average basis. However, because of a number of high-level samples, ranging up to 862 ppb, the mean level was more than twice the volume-weighted average that takes into account the market share represented by each winery. In this case, 24% of the 37 samples of dessert wine exceeded the 90 ppb goal for the 1995 harvest. It is important to note that these wines probably represent products that were produced before any of the previously mentioned recommendations for reducing E C levels in wine were implemented. The wine industry has been requested to reconsider their target levels based on these encouraging results. F D A has also alerted all countries that export alcoholic beverages to the U.S. of the need to develop E C programs with target goals similar to those adopted by the U.S. industry. Research papers published by workers in Britain, France, Germany, and Switzerland suggest that some progress has been made in understanding and controlling E C formation within these countries. Tanner (77), of the Swiss Federal Research Institute, has made recommendations for reducing E C in stone fruit brandies, which had the highest E C levels of any alcoholic beverage category. His first recommendation, similar to that of the U.S. industry, was to conduct more controlled distillations. This process change was probably intended to improve the efficiency of E C separation. His other recommendations were to distill the mash within 2 months and to stop crushing the stones or pits of the stone fruits. These recommendations apparently focus on reducing the release of potential E C precursors from the pits, such as cyanate and cyanic acid, which can react with vicinal dicarbonyl compounds such as diacetyl in the presence of ethanol to form EC. At this time we have no data on how effective these process recommendations have been in reducing E C levels in fruit brandy. In summary, it appears that both the U.S. distilled spirits and U.S. wine industries have made significant progress toward understanding and controlling E C formation and achieving their target goals. F D A will be involved in several future EC-related activities that will include (1) surveys of alcoholic beverages (by BATF) to monitor E C levels in commercial products; (2) monitoring results of the industries' sampling programs and progress in lowering E C levels; (3) evaluating the results of the National Toxicology Program and any other new toxicological studies, when available; and finally, (4) combining new toxicological information with updated exposure data to perform a quantitative assessment of the risk posed by E C in alcoholic beverages. F D A will also continue to work closely with the distilled spirits and wine industries in their efforts to reduce E C to the lowest levels technologically feasible. Literature Cited 1. 2.

3. 4.

Urethane in Alcoholic Beverages; Research and Survey Reports; Availability, Fed. Regist. March 23, 1990, 55, 10816-10817. Diachenko, G. W.; Canas, B. J.; Joe, F. L., Jr.; Havery, D. C. Presented at the International Office of Vine and Wine Meeting on Ethyl Carbamate, Paris, May 31, 1988. Lau, B.P.-Y.; Weber, D.; Page,D.B. J. Chromatogr. 1987, 402, 233-241. Canas, B. J.; Havery, D.C.; Robinson, L. R.; Sullivan, M. P.; Joe, F. L., Jr.; Diachenko, G. W. J. Assoc. Off. Anal. Chem. 1989, 72, 873-876.


428 5.

6. 7. 8.

9.


10. 11.

12.

13. 14. 15.

16.

17.

FOOD SAFETY ASSESSMENT Canas, B. J.; Joe, F. L., Jr.; Diachenko, G. W. Presented at the 104th Annual Meeting of the Association of Official Analytical Chemists, New Orleans, LA, September 1990; paper 126. Ough, C. S. J. Agric. Food Chem. 1976, 24, 323-328. Statistical Abstracts of the United States, U. S. Government Printing Office: Washington, DC, 1987. Frequency Distributions of the 14-Day Average Quantity ofFood Consumed by Age of Eater, Market Research Corporation of America report under FDA contract No. 223-87-2088, 1988. Foods Commonly Eaten by Individuals, U.S. Department of Agriculture Home Economics Research Report 44: Hyattsville, MD, 1982. MacKenzie, W. M.; Clyne, A. H.; MacDonald, L. S. J. Inst. Brew. 1990, 96, 223-232. Comments of the Distilled Spirits Council of the U.S. (Docket No. 86P-0482/ CP, EC File II, June 8, 1987), available from the FDA Hearing Clerk, Rockville, MD. Quarterly Reportsfromthe Distilled Spirits Council of the U.S. (Docket No. 89N-0483, letters from DISCUS to S. Delgado, July 14 and October 3, 1989 and January 30, 1990), availablefromIndustry Activities Section (HFF-326), FDA, Washington, DC. Ough, C. S. Proceedings of the Institute of Pathobiology Toxicology Forum, Aspen, CO, 1986, pp. 387-392. Ough, C. S.; Crowell, Ε. Α.; Mooney, L. A. Am. J. Enol. Vitic. 1988, 39(3), 243-249. Letter from the Wine Institute to FDA's C. Coker, dated March 10, 1989 (Docket No. 89N-0483), available from Industry Activities Section (HFF-326), FDA, Washington, DC. Letter from the Wine Institute to FDA's C. Coker, dated November 8, 1989 (Docket No. 89N-0483), availablefromthe Industry Activities Section (HFF326), FDA, Washington, DC. Tanner, H. Schweiz. Z. Obst. Weinbau 1986, 122(9), 260-262.

RECEIVED September 4, 1991


Ethyl Carbamate in Alcoholic Beverages and Fermented Foods - ACS

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