GRAS Notice (GRN) No. 761, Esterified Propoxylated Glycerol
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GRAS Notice (GRN) No. 761 https://www.fda.gov/food/generally-recognized-safe-gras/gras-notice-inventory February 20, 2018 Office ofFood Additive Safety HFS-200 Center for foodSafetyand Applied Nutrition food and Drug Administratioo 5001 Campus Drive College Park, MD, 20740 Dear Sir or Madam: Accompanying this letterisa notice pursuantto regulationsofthe Food and Orug Administration found at 21 CFR Part 170 settingforth the basis forthe conclusion reached by the submitter, Choco Finesse, LLC, that esterified propoxylated glycerol (EPG) is generally recognized as safe underthe intended conditions ofuse described in the notice. The notice is contained in a binder. In addition, we include a CD that contains a complete copyofthe notice. I hereby certify thatthe electronicfilescontained onthe flash drivewere scanned forviruses priorto submission, and thuscertified as beingvirus-free using Symantec Endpoint Protection. Sine I,/ .. (b) (6) '---'--------..... David Rowe President Phone: 317-694-3601 Email: drowe@chocofi nesse .com Ft -1 2 2 2018 z., ,..,.. ,. ; FOOD ADDITivE SAFETY GRAS NOTICE FOR ESTERIFIED PROPOXYLATED GLVCEROL {EPG) FOR USE IN SELECT COMMERCIAL FRYING APPLICATIONS Prepared for: Office of Food Additive Safety (HFS-200} Center for Food Safety and Applied Nutrition Food and Drug Administration 5001 Campus Drive College Park, MD 20740 Prepared by: Choco Finesse, LLC 5019 N. Meridian Street Indianapolis, Indiana 46208 February 20, 2018 rR1~~~~~~[Q) FEB 2 2 2018 OFFICE OF FOOD ADDmVE SAFETY GRAS Notice for Esterified Propoxylated Glycerol (EPG) for Use in Select Commercial Frying Applications TABLE OF CONTENTS Part 1. §170.225 Signed Statements and Certification ..................................................................................... 4 1.1 Name and Address of Notifier .................................................................................................. 4 1.2 Common Name of Notified Substance ..................................................................................... 4 1.3 Conditions of Use ...................................................................................................................... 5 1.4 Basis for GRAS ........................................................................................................................... 6 1.5 Availability of Information ........................................................................................................ 6 1.6 Freedom of Information Act, 5 U.S.C. 552 ................................................................................ 6 Part 2. §170.230 Identity, Method of Manufacture, Specifications, and Physical or Technical Effect ............. 7 2.1 Description ................................................................................................................................ 7 2.2 Manufacturing .......................................................................................................................... 7 2.2.1 Overview ...................................................................................................................... 7 2.2.2 Raw Material Specifications......................................................................................... 8 2.2.3 Detailed Description of the Manufacturing Process .................................................... 9 2.3 Product Specifications ............................................................................................................ 10 2.3.1 Proposed Chemical Specifications ............................................................................. 11 2.3.2 Microbiological Specifications ................................................................................... 14 2.4 Product Analysis ...................................................................................................................... 14 2.4.1 Chemical Analysis ...................................................................................................... 14 2.4.2 Microbiological Analysis ............................................................................................ 16 2.4.3 Additional Analytical Information .............................................................................. 16 Part 3. §170.235 Dietary Exposure .................................................................................................................. 19 3.1 History of Use in Food ............................................................................................................. 19 3.2 Intended Use of EPG and Levels of Use in Foods ................................................................... 19 3.3 Estimated Consumption of EPG from All Intended Conditions of Use in Food ...................... 25 3.3.1 Dietary Intake Survey ................................................................................................. 25 3.3.2 Estimated Consumption of EPG from Proposed Food-Uses ...................................... 26 3.3.3 Cumulative Intakes .................................................................................................... 28 Part 4. §170.240 Self-Limiting Levels of Use ................................................................................................... 28 Part 5. §170.245 Experience Based on Common Use in Food Before 1958 ................................................... 28 Part 6. §170.250 Narrative and Safety Information ........................................................................................ 29 6.1 Introduction ............................................................................................................................ 29 6.2 Literature Search..................................................................................................................... 30 6.3 Absorption, Distribution, Metabolism, and Excretion ............................................................ 30 6.3.1 ADME Studies ............................................................................................................ 31 6.4 Pivotal Toxicology Studies ...................................................................................................... 37 6.4.1 Repeat-Dose Toxicity ................................................................................................. 37 6.4.2 Reproductive and Developmental Toxicity Studies ................................................... 39 Choco Finesse, LLC 1 February 20, 2018 6.4.3 Genotoxicity Testing of Esterified Propoxylated Glycerol (EPG) (Bechtel, 2014) .......................................................................................................................... 40 6.5 Corroborative Evidence of Safety ........................................................................................... 45 6.5.1 Repeat-Dose Toxicity ................................................................................................. 45 6.5.2 Reproductive and Developmental Toxicity ................................................................ 51 6.5.3 Irritation and Sensitization Studies ............................................................................ 53 6.6 Clinical Safety .......................................................................................................................... 55 6.6.1 Tolerance Studies with H-EPG-05 HR/SO (9:1) .......................................................... 58 6.6.2 Tolerance Studies with EPG-05 HR/ST 45:55 (Softer Version on EPG) ...................... 58 6.7 Information Potentially Inconsistent with GRAS .................................................................... 66 6.7.1 Gastrointestinal Discomfort ....................................................................................... 66 6.7.2 Effect on Nutrient (Fat-Soluble Vitamin) Status ........................................................ 66 6.7.3 Effect on β-Carotene Levels ....................................................................................... 70 6.7.4 Effect on Serum HDL Levels ....................................................................................... 70 6.7.5 Effect on Serum Transaminase Levels ....................................................................... 73 6.8 Expert Panel Evaluation .......................................................................................................... 77 6.9 Conclusions ............................................................................................................................. 78 Part 7. §170.255 List of Supporting Data and Information ............................................................................. 79 List of Appendices Appendix 1 Certificate of Analysis – Propylene Oxide Appendix 2 Tocopherol Safety Summary Appendix 3 Estimated Daily Intake of Esterified Propoxylated Glycerol (EPG) by the U.S. Population from intended Frying Applications (2013-2014 NHANES) Appendix 4 Expert Panel Consensus Statement List of Figures and Tables Figure 2.2-1 Schematic Overview of the Manufacturing Process for EPG.................................................. 8 Figure 6.6.2.3-1 Mean Retinol Levels Over Time ............................................................................................ 62 Figure 6.6.2.3-2 Mean α-Tocopherol Levels Over Time ................................................................................. 63 Figure 6.6.2.3-3 Mean Circulating 25-OH D2 (Ergocalciferol) Levels Over Time ............................................ 64 Figure 6.6.2.3-4