Consultation Document on Health Canada's Proposal to Enable the Use of a New Food Additive, Urease, as a Food Enzyme in Wine and Sake

Notice of Proposal - Lists of Permitted Food Additives

March 11, 2013

Summary

Food additives are regulated in Canada under the Food and Drug Regulations and Marketing Authorizations (MAs) issued by the Minister of Health. Approved food additives and their permitted conditions of use are set out in the Lists of Permitted Food Additives that are incorporated by reference in the MAs. A petitioner can request that Health Canada approve a new food additive or a new condition of use for an already approved food additive by filing a food additive submission with the Department's Food Directorate. Health Canada uses this premarket approval process to determine whether the scientific data support the safety of food additives when used under specified conditions in foods sold in Canada.

Health Canada received a food additive submission seeking approval for the use of urease, obtained from Lactobacillus fermentum, in the manufacture of wine. Urease is a food enzyme that could be used to reduce the formation of ethyl carbamate, a suspected human carcinogen that can form during the wine making process. As additional data related to the ability of urease to reduce ethyl carbamate formation during sake making was also available to the Department, the scope of the original safety evaluation was expanded to include sake.

The results of Health Canada's evaluation of available scientific data support the safety and efficacy of urease when used for this purpose. Therefore, it is the intention of Health Canada to modify the List of Permitted Food Enzymes by adding the entry shown below to the list:

Rationale

Health Canada's Food Directorate has completed a pre-market safety and efficacy assessment of the enzyme urease for use in winemaking and sake making to reduce the formation of ethyl carbamate. The assessment considered toxicological, chemical, microbiological, nutritional and technical aspects of the proposal.

Ethyl carbamate is a suspected human carcinogen that can form during the fermentation of alcoholic beverages. Health Canada has set maximum levels (standards) for ethyl carbamate in certain alcoholic beverages including wines and sake.

The formation of ethyl carbamate in wine begins with arginine, an amino acid naturally present in foods. In wine, arginine is taken up by yeast as a nutrient, and if it is present in excessive amounts, it may be metabolized by the yeast to yield urea. If the resulting urea is not further metabolized and accumulates in the yeast cell above a critical concentration, the yeast release it from their cells into the wine during or at the end of fermentation. The urea can then react with the ethanol during wine fermentation to form ethyl carbamate.

Urease can reduce the formation of ethyl carbamate by hydrolysing urea to ammonia and carbon dioxide. This reduces the amount of urea that would otherwise be available to react with ethanol to form ethyl carbamate. Available scientific information indicates that urease is effective at reducing the formation of ethyl carbamate in both wine and sake. There is no health concern with the ammonia and carbon dioxide that result from the action of urease.

Health Canada reviewed the results of safety studies that were designed to specifically examine whether urease could cause harmful health effects. These studies investigated whether the consumption of urease could adversely affect the health of laboratory animals (acute and short-term oral toxicity studies) and whether urease could cause mutations (genetic toxicity studies). The data from these studies support the safety of urease, obtained from Lactobacillus fermentum, when used as proposed in the manufacturing of wine and sake.

The enzyme preparation contains the source organism Lactobacillus fermentum in a non-viable state in addition to the enzyme. Lactobacillus fermentum is a microorganism (bacterium) that can be found in a variety of foods and it has not been associated with adverse allergenic reactions. Consequently, the urease enzyme preparation from this microorganism is not considered to pose an allergenic risk when consumed in wine and sake. Urease enzyme is obtained from a non-genetically modified strain of Lactobacillus fermentum that is deemed to be non-pathogenic and non-toxicogenic.

No toxicological, microbiological or nutritional safety concerns were identified with respect to the use of urease, obtained from Lactobacillus fermentum, in wine or sake manufacture to reduce the formation of ethyl carbamate. Based on the results of the food additive submission evaluation, Health Canada's Food Directorate considers that the available data support the safety and efficacy of urease obtained from Lactobacillus fermentum under the conditions of use set out in the table above. The Department is therefore proposing to enable the use of urease as described in the table. This would provide manufacturers with another tool for enhancing the safety of their wine and sake products by reducing the formation of ethyl carbamate in these beverages.

Other Relevant Information

In Australia and New Zealand, urease obtained from Lactobacillus fermentum may be used as a processing aid in the course of manufacture of any food.

The European Union permits urease to be used in winemaking at a maximum level of 75 mg of urease preparation per litre of wine, and requires that after treatment all residual enzyme activity must be eliminated by filtering the wine.

Urease obtained from Lactobacillus fermentum has had a history of food use in Japan for the reduction of ethyl carbamate in all alcoholic beverages since 1987.

In the United States, urease enzyme preparation obtained from Lactobacillus fermentum is affirmed as generally recognized as safe (GRAS) when used for treatment of wine (which includes sake) to inhibit the formation of ethyl carbamate. The amount used to treat the wine is limited to not more than 200 mg/L and must be filtered prior to final packaging of the wine.

The Office International de la Vigne et du Vin (OIV), an intergovernmental organization consisting of 35 member countries, accepts the use of urease, obtained from Lactobacillus fermentum, in winemaking to reduce the level of urea in wine as a means to reduce the formation of ethyl carbamate.

Wine has a compositional standard (section B.02.100 [S], Division 2 of the Food and Drug Regulations. The use of urease in wine manufacturing in Canada is supported by several associations that represent this industry. Health Canada also consulted provincial and territorial liquor authorities regarding the use of urease in winemaking. The responses received indicated that there were no objections to the use of urease in the winemaking process.

The Food and Drug Regulations require that all food enzymes, including urease, used in foods sold in Canada meet the specifications for enzyme preparations prescribed in the most recent edition of the Food Chemicals Codex, a compendium of standards for purity and identity of food ingredients, including food additives, which is published by the United States Pharmacopeial Convention.

Implementation and enforcement

The proposed change will be effective the day on which they are published in the List of Permitted Food Enzymes. This will be announced via a Notice of Modification which will be published on Health Canada's website.

The Canadian Food Inspection Agency is responsible for the enforcement of the food-related aspects of the Food and Drugs Act and its associated regulations.

Contact Information

For additional information or to submit comments related to this proposal, please contact:

Bureau of Chemical Safety
251 Sir Frederick Banting Driveway
Tunney's Pasture, PL: 2202C
Ottawa, Ontario K1A 0L2

E-mail: mailto:bcs-bipc@hc-sc.gc.ca

If communicating by e-mail, please use the words "Urease Notification" in the subject line of your e-mail. Health Canada is able to consider information received by May 24 2013, 75 days from the date of this posting.