Agency Response Letter GRAS Notice No. GRN 000307
CFSAN/Office of Food Additive Safety
April 23, 2010
Ms. Rosidah Radzian
Malaysian Palm Oil Board TAS America
3516 International Ct., N.W.
Washington, DC 20008
Re: GRAS Notice No. GRN 000307
Dear Ms. Rosidah Radzian:
The Food and Drug Administration (FDA) is responding to the notice, dated October 19, 2009, that Nutrasource, Inc. submitted on behalf of the Malaysian Palm Oil Board TAS America (MPOB) in accordance with the agency's proposed regulation, proposed 21 CFR 170.36 (62 FR 18938; April 17, 1997; Substances Generally Recognized as Safe (GRAS); the GRAS proposal). FDA received the notice on October 23, 2009, filed it on October 27, 2009, and designated it as GRAS Notice No. GRN 000307. In an email of January 13, 2010, Nutrasource, Inc. requested FDA respond directly to MPOB.
The subject of the notice is palm oil-derived tocols with tocotrienols (T3)1 and α-tocopherol (α-T) as the principal components (hereinafter referred to as PODT). The notice informs FDA of the view of MPOB that PODT are GRAS, through scientific procedures, for use as an ingredient as listed in Table 1.
|Food Category, Serving Size||Use Levels (milligram (mg)/ serving)|
|Margarine and spread, 1 tsp = 13.6 gram (g)||1.53||0.51|
|Designer fats and oil, 1 tsp = 13.6 g||1.53||0.51|
|Salad dressing and mayonnaise, 27.2 g||1.02||0.34|
|Potato chips and salty snacks, 30 g||1.125||0.375|
|Bakery products (breads, rolls and croissants), 30-50 g||1.125||0.375|
|Cookies and crackers, 25 g||0.94||0.31|
|RTE cereals, cereal bars, granola bars, protein bars and power bars, 30 g||5.6||1.9|
|Meal replacement and other functional beverage products (240 g) and mixes||5.4||1.8|
|Meatless meat products (soy based), 70 g||0.79||0.26|
|Meatless soups (240 g) and soup mix||2.02||0.68|
|Meatless gravies, sauces and pasta sauces, 70 g||0.68||0.22|
|Processed juice, 240 g||5.4||1.8|
|Processed fruits, juice drinks and punch, 240 g||2.7||0.9|
|Soft drinks, 240 g||1.8||0.6|
|Frozen dairy desserts and mixes, ½ C = 68 g||1.02||0.34|
|Yogurt, pudding and jello, 240 g||3.6||1.2|
|Chocolate milk, flavored milk, soy milk and products, 240 g||5.4||1.8|
|Chocolate, candy, confectionary and sweets, 43 g||1.8||0.6|
|Chewing gum, 1 stick||0.045||0.015|
21 CFR 101.4 states that all ingredients must be declared by their common or usual name. In addition, 21 CFR 102.5 outlines general principles to use when establishing common or usual names for nonstandardized foods. Our use of PODT in this letter should not be considered an endorsement or recommendation of that term as an appropriate common or usual name for the purpose of declaring the substance in the ingredient statement of foods that contain that ingredient. Issues associated with labeling and the appropriate common or usual name of a food are the responsibility of the Office of Nutrition, Labeling and Dietary Supplements (ONLDS) in the Center for Food Safety and Applied Nutrition.
As part of its notice, MPOB includes the report of a panel of individuals (MPOB's GRAS panel) who evaluated the data and information that are the basis for MPOB's GRAS determination. MPOB considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. MPOB's GRAS panel evaluated estimates of dietary exposure, method of production, and product specifications as well as published safety studies. Based on this review, MPOB's GRAS panel concluded that PODT, that meets established food grade specifications are GRAS under the conditions of their intended use.
MPOB provides information about the identity and composition of PODT. PODT are extracts of palm oil that are rich in T3 and α-T. T3 and α-T, as well as β-, γ- and δ-tocopherol, constitute a group of compounds that possess vitamin E activity. PODT are manufactured in a variety of ways to produce products that are reddish oil suspensions, dry stabilized orange powders, light amber suspensions, clear orange-color liquids, slightly viscous orange liquids, and slight orange beadlets. MPOB states that in all formulations, α-T is 20-30% of the total T3 plus α-T present (i.e., 1.5% - 80% for all formulations).
MPOB describes the method of manufacture for PODT. The starting raw material for all the varieties of PODT is crude palm oil obtained from the mesocarp of the oil palm. First, the triglycerides in crude palm oil are converted to methyl esters, which are then removed via a molecular distillation process at low temperature and under high vacuum. Alternatively, crude palm oil is degummed by reacting it with food grade phosphoric acid. The concentrated residue containing PODT is subjected to various additional processing steps to remove the remaining impurities. The resulting product is PODT in oil suspension. Additional processes are used to prepare other forms of PODT. For example, to prepare a water soluble emulsion, PODT in oil suspension is mixed with emulsifiers. To prepare a water-dispersible powder, PODT in oil suspension is mixed with a powder carrier and then dried and milled or alternatively spray dried into a powder. The notice includes the use of ingredients that either approved food additives or whose use is GRAS in all formulations of PODT.
MPOB provides specifications for PODT. These specifications include the ranges of various T3, α-T, and palm oil; limits for moisture content and impurities (e.g., phytosterols, squalene), microorganisms, lead ((less than 0.5 mg/kilogram (kg)), and added ingredients (e.g., glycerin). MPOB states that in all formulations α-T is 20-30% of the total T3 and α-T present.
MPOB estimates the daily intakes of T3 and α-T from the intended food uses of PODT using data available from the National Center for Health Statistics' 2005-6 National Health and Nutrition Examination Survey. Assuming that 100% of the products in each food category will contain the ingredient, the notifier estimates the intake at the 90th percentile level for users above 1 year of age would be 0.99 mg/kg body weight per day (mg/kg bw/d) for T3, and 0.43 mg/kg bw/d for α-T.
MPOB discusses the safety of PODT, T3 found in PODT, and tocopherols in general. The notifier discusses several published animal or human studies where the subjects received PODT (up to 5000 mg/kg bw/d for animals or 472 mg/kg bw/d for humans) or T3 (5 mg/kg bw/d for animals only) with no abnormalities or adverse effects observed. MPOB also discusses published studies of acute, subchronic, and chronic animal studies as well as human clinical studies related to tocopherols. Regarding tocopherols, the notifier notes that α-T is listed as GRAS in 21 CFR 184.1890 as an inhibitor of nitrosamine formation and as an ingredient in pump cured bacon at a level not to exceed current good manufacturing practice (cGMP). The notifier also notes that tocopherols and α-T acetate are listed as GRAS in 21 CFR 182.8890 and 182.8892, respectively, as nutrients with no other limitations than cGMP. In addition, the Food and Nutrition Board of the Institute of Medicine has set the tolerable upper intake level of α-T for adults at 17 mg/kg bw/d, assuming a 60 kg person. Based on the totality of this information, MPOB considers PODT safe for its intended use.
Standards of Identity
In the notice, MPOB states its intention to use PODT in several food categories, including foods for which standards of identity exist, located in Title 21 of the Code of Federal Regulations. We note that an ingredient that is lawfully added to food products may be used in a standardized food only if it is permitted by the applicable standard of identity.
Potential Labeling Issues
Under section 403(a) of the Federal Food, Drug, and Cosmetic Act (FFDCA), a food is misbranded if its labeling is false or misleading in any particular. Section 403(r) of the FFDCA lays out the statutory framework for the use of labeling claims that characterize the level of a nutrient in a food or that characterize the relationship of a nutrient to a disease or health-related condition. In describing the intended use of PODT and in describing the information that MPOB relies on to conclude that PODT are GRAS under the conditions of their intended use, MPOB raises a potential issue under these labeling provisions of the FFDCA. If products that contain PODT bear any claims on the label or in labeling, such claims are the purview of ONLDS. The Office of Food Additive Safety neither consulted with ONLDS on this labeling issue nor evaluated the information in your notice to determine whether it would support any claims made about PODT on the label or in labeling.
Potential Requirement for a Color Additive Petition
In its notice, MPOB describes the concentrate that it uses to prepare its PODT. As such, the use of PODT in food products may constitute the use of a color additive under section 201(t)(1) of the FFDCA and FDA's implementing regulations in 21 CFR Part 70. Under section 201(t)(1) and 21 CFR 70.3(f), the term color additive means a material that is a dye, pigment, or other substance made by a process of synthesis or similar artifice, or extracted, isolated, or otherwise derived from a vegetable, animal, mineral, or other source, and that is capable (alone or through reaction with another substance) of imparting color when added or applied to a food; except that such term does not include any material which the Secretary,2 by regulation, determines is used (or intended to be used) solely for a purpose or purposes other than coloring. Under 21 CFR 70.3(g), a material that otherwise meets the definition of color additive can be exempt from that definition on the basis that it is used or intended to be used solely for a purpose or purposes other than coloring, as long as the material is used in a way that any color imparted is clearly unimportant insofar as the appearance, value, marketability, or consumer acceptability is concerned. Given the construct of section 201(t)(1) of the FFDCA and 21 CFR 70.3(f) and (g), the use of a substance that is capable of imparting color may constitute use as a color additive in addition to use as a food additive or GRAS substance. For example, beta-carotene is both approved for use as a color additive (21 CFR 73.95) and affirmed as GRAS for use as a nutrient supplement (21 CFR 184.1245); in some food products, beta-carotene is used for both purposes. Importantly, if the use of PODT constitutes use as a color additive within the meaning of section 201(t)(1) of the FFDCA and FDA's implementing regulations in 21 CFR 70.3(f) and (g), section 721(a) of the FFDCA requires premarket review and approval of that use by FDA. Under section 402(c) of the FFDCA, a food product that contains an unapproved color additive would be deemed adulterated.3
In a telephone conference on March 23, 2010, between FDA and Nutrasource, Inc., FDA requested that MPOB present its view on whether any of the intended uses of PODT would be exempt from the definition of a color additive. In an amendment dated March 25, 2010, MPOB presented its reason for concluding that all of the intended uses of PODT would be exempt from the definition of color additive under section 201(t) of the FFDCA and FDA's implementing regulations in 21 CFR 70.3(f) and (g). Importantly, FDA's response to GRN 000307 does not include any comment by FDA about MPOB's view on this issue. If, after receipt of this letter, MPOB has any further questions about this issue, we recommend that MPOB contact the Division of Petition Review in the Office of Food Additive Safety.
Section 301(ll) of the FFDCA
The Food and Drug Administration Amendments Act of 2007, which was signed into law on September 27, 2007, amends the FFDCA to, among other things, add section 301(ll). Section 301(ll) of the FFDCA prohibits the introduction or delivery for introduction into interstate commerce of any food that contains a drug approved under section 505 of the FFDCA, a biological product licensed under section 351 of the Public Health Service Act, or a drug or a biological product for which substantial clinical investigations have been instituted and their existence made public, unless one of the exemptions in section 301(ll)(1)-(4) applies. In its review of MPOB's notice that PODT are GRAS for their intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing PODT. Accordingly, this response should not be construed to be a statement that foods that contain PODT, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by MPOB, as well as other information available to FDA, the agency has no questions at this time regarding MPOB's conclusion that PODT are GRAS under the intended conditions of use. The agency has not, however, made its own determination regarding the GRAS status of the subject use of PODT. As always, it is the continuing responsibility of MPOB to ensure that food ingredients that the firm markets are safe, and are otherwise in compliance with all applicable legal and regulatory requirements.
In accordance with proposed 21 CFR 170.36(f), a copy of the text of this letter responding to GRN 000307, as well as a copy of the information in this notice that conforms to the information in the GRAS exemption claim (proposed 21 CFR 170.36(c)(1)), is available for public review and copying via the FDA home page at http://www.fda.gov. To view or obtain an electronic copy of the text of the letter, follow the hyperlinks from the "Food" topic to the "Food Ingredients and Packaging" section to the "Generally Recognized as Safe (GRAS)" page where the GRAS Inventory is listed.
Mitchell A. Cheeseman, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
1T3 is a mixture of α-, β-, γ- and δ-tocotrienol.
2The Secretary of the Department of Health and Human Services
3We note that section 721(b)(4) of the FFDCA provides that a color additive shall be deemed to be safe and suitable for the purpose of listing under section 721(b) of the FFDCA while there is in effect a published finding of the Secretary declaring that the substance is exempt from the definition of “food additive” because of its being generally recognized by qualified experts as safe for its intended use as provided in section 201(s) of the FFDCA. Importantly, FDA’s response to GRN 000307 does not constitute a “finding of the Secretary” within the meaning of section 721(b)(4) of the FFDCA.