Decision on theobromine as a supplemental ingredient in foods

Health Canada's Food and Nutrition Directorate has assessed theobromine for use as a supplemental ingredient. This is one of the ingredients the Food and Nutrition Directorate identified for further assessment as set out in Health Canada's Category Specific Guidance for Temporary Marketing Authorization: Supplemented Food.^{Footnote 1}

The assessment considered publicly available information and found the data insufficient to establish acceptable conditions for its use as a supplemental ingredient in foods.

Consequently, Health Canada is not acceding to the use of theobromine as a supplemental ingredient. While theobromine occurs naturally in some foods and has a history of use as a food ingredient (e.g., use as a flavouring), the available information is insufficient to assess the safety of theobromine for use as a supplemental ingredient. The food seller is responsible for ensuring that the sale of a food containing theobromine does not contravene section 4 of the Food and Drugs Act.

Health Canada is prepared to accept a request to reconsider this decision under the regulations for supplemented foods. The Appendix of this letter identifies the information required to support reconsideration.

For more information on Health Canada's decision on theobromine, please contact the Food and Nutrition Directorate's Submission Management and Information Unit (SMIU) (E-mail: smiu-ugdi@hc-sc.gc.ca). Please use the words "Decision on Theobromine" in the subject line of your e-mail.

Appendix – Information to support a request for Health Canada to reconsider the decision on the use of theobromine as a supplemental ingredient

General guidance

1. Characterise in detail the theobromine that is requested for use.
2. Clearly demonstrate that the toxicological and nutritional safety information apply to use of the requested theobromine as a supplemental ingredient in foods.
3. Provide full study reports of safety tests (e.g., pre-clinical and/or clinical), not summaries. The reports should provide clear, detailed characterisation of the theobromine test material and a full description of the study design, including methods used, the type and number of animals treated, the doses administered and the end-points measured. Studies should also provide detailed documentation of the test results.

Toxicological information

1. Information on the human health relevance of the laboratory animal models. This information is used to determine the applicability of the varied results of animal-based toxicological studies for theobromine proposed for addition to food as a supplemental ingredient. Depending on the results of this critical data gap, additional toxicology studies may be required, such as:
2. Repeated dose toxicity testing, in a relevant animal model, of orally administered theobromine at doses that would provide adequate evidence of safety to support its use as a supplemental ingredient in food.
3. Genotoxicity testing of theobromine. In general, a basic test battery would be comprised of two or more in vitro tests, or in vitro tests plus an in vivo test (in a relevant animal model) to evaluate genotoxic potential. In vivo studies should be conducted via the oral route of exposure.
4. Reproductive and developmental toxicity testing, in a relevant animal model, of orally administered theobromine at doses that would provide adequate evidence of safety to support its use as a supplemental ingredient, suitable for consumption by the general population, including foods that could be consumed by children and individuals who are pregnant or who are trying to become pregnant.
5. In the absence of a relevant animal model, human clinical studies, of orally administered theobromine at doses that would provide adequate evidence of safety (i.e., from both a toxicological and nutritional perspective) to support its use as a supplemental ingredient in food.

Nutritional information

1. Information that would provide adequate evidence that theobromine would not affect digestion or absorption of other nutrients, especially in the intestines, and/or information that theobromine would not pose nutritional safety concerns if foods supplemented with theobromine were to be consumed frequently over a long period of time in different food matrices.

This information is required to address the safety of theobromine for use as a supplemental ingredient in foods, not to demonstrate efficacy or to support specific health claims. For substantiation of food health claims, please see Health Canada's guidance Substantiation of Health Claims (Scientific Evidence).^{Footnote 2}