Notice of Modification to the List of Permitted Food Enzymes  to Enable  
the Use of Urease  as a Food Enzyme in Wine and Sake   
Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch     1 
  
Notice of Modification to the List of Permitted 
Food Enzymes  to Enable the Use of Urease as a 
Food Enzyme in Wine and Sake  
 
Notice of Modification – Lists of Permitted Food Additives  
Reference Number: [NOM/ADM -0016] 
 
 
 September 3 , 2013   
Notice of Modification to the List of Permitted Food Enzymes  to Enable  
the Use of Urease  as a Food Enzyme in Wine and Sake   
Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch     2 Summary  
 
Food additives are regulated in Canada under Marketing Authorizations  (MAs) issued by the 
Minister of Health and the Food and Drug Regulations.  Approved food additives and their 
permitted conditions of use are set out in the Lists of Permitted Food Add itives  that are 
incorporated by reference in the MAs.  A petitioner can request that Health Canada approve a 
new 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 the enzyme 
urease obtained from Lactobacillus fermentum  in the manufacture of wine to reduce the 
formation of ethyl carbamate.  Ethyl carbamate is a suspected human carcinoge n that can form 
during the manufacture of wine . As additional data related to the ability of urease to reduce ethyl 
carbamate formation during the manufacture of sake 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 as set out in the table below. Since this is a food additive that was 
not previously permitted for use i n Canada, Health Canada published, on March 11, 2013, a 
Notice of Proposal to e nable the use of a new food additive, urease, as a food enzyme in wine 
and sake  and requested comments on the proposal.  Since n o new scientific information was 
submitted to the Department as a result of this publication , and s ince the conclusions of the 
evaluation remain as described in the publication, Health Canada has modified the List of 
Permitted Food Enzymes  as indicated below.   
 
Modification to the List of Permitted Food Enzymes  
 
Item 
No. Column 1  
Additive  Column 2  
Permitted 
Source  Column 3  
Permitted in or 
Upon  Column 4  
Maximum Level of Use and 
Other Conditions  
U.1 Urease  Lactobacillus 
fermentum  Sake; Wine  Good Manufacturing Practice  
 
Rationale  
 
Health Canada's Food Directorate completed a pre -market safety and efficacy assessment of the 
enzyme urease for use in the manufacture of wine and sake  to reduce the formation of ethyl 
carbamate. The assessment considered toxicological, chemical, microbiological, nutritional and 
technical aspects of urease when used as set out in the table above.  
  
Notice of Modification to the List of Permitted Food Enzymes  to Enable  
the Use of Urease  as a Food Enzyme in Wine and Sake   
Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch     3 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 wine and sake.  
 
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 availabl e 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 res ult from the action of urease.  
 
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 co nditions of use set out in the table above. The 
Department has therefore enabled the use of urease as described above. This will provide 
manufacturers with another tool for enhancing the safety of their wine and sake products by 
reducing the formation of e thyl carbamate in these beverages.  
 
Other Relevant Information  
 
Urease is permitted for use in wine  manufacturing  in Australia, the European Union, New 
Zealand and the United States.  
 
Wine has a compositional standard set out in section B.02.100 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 the ma nufacture of wine. The responses received 
indicated that there were no objections to the use of urease in the manufacture of wine.  
 
The Food and Drug Regulations  require that all food enzymes, including urease, used as food 
additives meet the specification s for enzyme preparations prescribed in the most recent edition of 
the Food Chemicals Codex (FCC) .  The FCC is a compendium of standards for purity and 
identity of food ingredients, including food additives, which is published by the United States 
Pharmaco peial Convention.  
  
Notification – Summary of Comments   
 
In response to the Notice of Proposal to e nable the use of urease as a food enzyme in wine and 
sake, published on March 11, 2013 , Health Canada did not receive any objections or new 
scientific information.   
 
 
   
Notice of Modification to the List of Permitted Food Enzymes  to Enable  
the Use of Urease  as a Food Enzyme in Wine and Sake   
Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch     4  
Implementation and Enforcement  
 
The above modification came into force on September  3, 2013 , the day it was published in the 
List of Permitted Food Enzymes . 
 
The Canadian Food Inspection Agency is responsible for the enforcement of the Food and Drugs 
Act and its associated regulations with respect to foods.  
 
Contact Information  
Health Canada's Food Directorate is committed to reviewing any new scientific information on 
the safety in use of any food additive, including urease. Anyone wishing to submit new scientific 
information on the use of this additive or to submit any inquiries may do so in writing, by regular 
mail or electronically. If you wish to contact the Food Directorate electronically, please use the 
words " urease " in the subject line of your e -mail. 
 
   Bureau of Chemical Safety  
   251 Sir Frederick Banting Driveway  
   Tunney’s Pasture, PL: 2202C  
   Ottawa, Ontario K1A 0 K9 
   E-mail:  bcs-bipc@hc -sc.gc.ca