GRAS Notice (GRN) No. 893 https://www.fda.gov/food/generally-recognized-safe-gras/gras-notice-inventory. Tox• Strategi.es Innovative solutions Sound science December 3, 2019 Office of Food Additive Safety (HFS-200) Center for Food Safety and Applied Nutrition Food and Drug Administration 500 I Campus Drive College Park, MD 20740-3835 Subject: GRAS Notification-Allulose Dear Sir: On behalf of Tate & Lyle., ToxStrategies, Inc. (its agent) is submitting, for FDA review, a copy of the GRAS notification as required. The enclosed document provides notice of a claim that the food ingredient, allulose, described in the enclosed notification is exempt from the premarket approval requirement of the Federal Food, Drug, and Cosmetic Act because it has been determined to be generally recognized as safe (GRAS), based on scientific procedures, for addition to food. In addition, non-safety related data and information (marked as confidential; Exhibit 2) are attached to the GRAS notice that are to be shared with the Food Safety Inspection Service (PSIS) of the U.S. Department of Agriculture (USDA). If you have any questions or require additional information, please do not hesitate to contact me at 630-352-0303, or [email protected]. Sincerely, Donald F. Schmitt, M.P .H. Senior Managing Scientist ~~~~"YJ~(Q) DEC 6 2019 OFFICE OF FOOD ADDITIVE SAFETY ToxStrategies, Inc., 931 W. 75th St., Suite 137, PMB 255, Naperville, IL 60565 Office (630) 352-030 • www.toxstrategies.com GRAS Determination of Allulose for ·.· ;;/. ,; "i· Use as an lngredie-nt in Human Food OCTOBER 11,~2§19 .. ;·~, DEC 6 2019 OFFICE OF FOOD ADDmVE SAFETY Innovative solutions Sound science GRAS Determination of Allulose for Use as an Ingredient in Human Food SUBMITTED BY: Tate & Lyle 5450 Prairie Stone Parkway Hoffman Estates, IL 60192 SUBMITTED TO: U.S. Food and Drug Administration Center for Food Safety and Applied Nutrition Office of Food Additive Safety HFS-200 5001 Paint Branch Parkway College Park MD 20740-3835 CONTACT FOR TECHNICAL OR OTHER INFORMATION Donald F. Schmitt, MPH ToxStrategies, Inc. 931 W. 75 th St., Suite 137, PMB 255 Naperville, IL 60565 October 11, 2019 2 Table of Contents § 170.225 Part 1, GRAS Notice: Signed Statements and Certification ........................ 6 (1) GRAS Notice Submission ..................................................................................................... 6 (2) Name and Address ................................................................................................................ 6 (3) Name of Notified Substance ................................................................................................. 6 (4) Intended Use in Food ............................................................................................................ 6 (5) Statutory Basis for GRAS Determination .......................................................................... 6 (6) Premarket Approval Statement .......................................................................................... 6 (7) Availability of Information .................................................................................................. 6 (8) Data and Information Confidentiality Statement ............................................................. 7 (9) GRAS Certification .............................................................................................................. 7 (10) Name/Position of Notifier ................................................................................................... 7 (11) FSIS Statement ................................................................................................................... 7 § 170.230 Part 2, Identity, Method of Manufacture, Specifications, and Physical or Technical Effect ................................................................................................................. 8 A. Identity ............................................................................................................................... 8 C. CAS Registry Number ...................................................................................................... 8 D. Trade Name ........................................................................................................................ 8 E. Empirical Formula and Chemical Structure of Allulose ............................................... 8 F. Allulose Composition ........................................................................................................ 8 G. Manufacturing Process ..................................................................................................... 9 H. Product Specifications ..................................................................................................... 12 I. Stability Data ................................................................................................................... 15 § 170.235 Part 3, Dietary Exposure ............................................................................... 16 Current Uses ............................................................................................................................. 16 Proposed Uses ........................................................................................................................... 18 § 170.240 Part 4, Self-Limiting Levels of Use ............................................................... 22 § 170.245 Part 5, Experience Based on Common Use in Food ................................... 23 § 170.250 Part 6, GRAS Narrative ................................................................................ 24 History of Use and Regulatory Approval............................................................................... 24 Safety ......................................................................................................................................... 24 Introduction .................................................................................................. ........... .......................... ............. 24 Absorption, Distribution, Metabolism, and Excretion (ADME) ................................................ 24 Animal Studies .......................................................................................................................... 27 Acute Toxicity ............................................. .......................................................................... ...... ................... 27 Subchronic toxicity ................................................ .......................................................................... ..... ....... 2 7 Chronic toxicity ................................................................ ... .................................... ...................................... 28 Reproductive toxicity ........... .. ........................................................... .......................................................... 29 Mutagenicity /genotoxicity .................................................................................................................. .. ... 29 Human Studies ......................................................................................................................... 30 Effect on Insulinemic and Glycemic Response ...................................................................... 34 Safety Summary ....................................................................................................................... 36 Basis for the GRAS Determination ............................................................................... 3 7 Introduction .............................................................................................................................. 37 Safety Determination ............................................................................................................... 38 General Recognition of the Safety of Allulose ....................................................................... 38 3 § 170.250 Part 7, Supporting Data and Information ...........................................•....... 41 References ................................................................................................................................. 41 Appendix A Pariza and Johnson Decision Tree Appendix B COAs and Other Analytical Data Appendix C Stability Testing Data Appendix D Intake Assessment Report Exhibit I Report of Expert Panel 4 List of Acronyms ADME absorption, distribution, metabolism, and excretion AUC area under the curve bw body weight CDC Centers for Disease Control and Prevention cGMP current Good Manufacturing Practice CAS Chemical Abstracts Service CED! cumulative estimated daily intake CFR Code of Federal Regulations CFU colony-forming units COA Certificate of Analysis dpm disintegrations per minute FDA U.S. Food and Drug Administration GRAS Generally Recognized as Safe GRN Generally Recognized as Safe Notification LDso lethal dose NHANES US National Health and Nutrition Examination Survey NOAEL no-observed-adverse-effect level SCFA short-chain fatty acid USDA United States Department of Agriculture WWEIA What We Eat in America 5 § 170.225 Part 1, GRAS Notice: Signed Statements and Certification (1) GRAS Notice Submission Tate & Lyle (T&L), through its agent, ToxStrategies, Inc., hereby notifies the U.S. Food and Drug Administration (FDA) of the submission of a Generally Recognized as Safe (GRAS) notice for the use of allulose in selected foods for human