Agency Response Letter GRAS Notice No. GRN 000332
CFSAN/Office of Food Additive Safety
September 24, 2010
Jaap D. Kluifhooft
Lipid Nutrition B. V.
1521 AZ Wormerveer
Re: GRAS Notice No. GRN 000332
Dear Mr. Kluifhooft:
The Food and Drug Administration (FDA) is responding to the notice, dated March 24, 2010, that you submitted 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 March 30, 2010, filed it on March 31, 2010, and designated it as GRAS Notice No. GRN 000332.
The subject of the notice is oil from the seeds of the Korean pine (Pinus koraiensis) (Korean-pine nut oil). The notice informs FDA of the view of Lipid Nutrition B.V. (Lipid Nutrition) that Korean-pine nut oil is GRAS, through scientific procedures, for use as a replacement for other oils at a level of 3.0 grams (g) per serving in baked goods and baking mixes, beverages and beverage bases, breakfast cereals, dairy product analogs, fats and oils, grain products and pasta, milk and milk products, nuts and nut products, processed fruit and fruit juices, processed vegetables and vegetable juices, snack foods, soft candy, and soups and soup mixes. Lipid Nutrition states that the intended use of Korean-pine nut oil does not include any meat or meat-containing products.
Our use of “Korean-pine nut oil” 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. Title 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. 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, Lipid Nutrition includes the report of a panel of individuals (Lipid Nutrition’s GRAS panel) who evaluated the data and information that are the basis for Lipid Nutrition’s GRAS determination. Lipid Nutrition considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Lipid Nutrition's GRAS panel evaluated the method of manufacture, product specifications, intended uses, estimates of dietary exposure, and the available scientific literature pertaining to the safety of Korean-pine nut oil. Based on this review, Lipid Nutrition’s GRAS panel concluded that Korean-pine nut oil meeting appropriate food grade specifications is GRAS under the conditions of its intended use.
Lipid Nutrition describes the identity, composition, and method of manufacture of Korean-pine nut oil (CAS No. 84988-87-4).1 Lipid Nutrition’s Korean-pine nut oil is obtained from Korean pine (Pinus koraiensis). It is a pale yellow clear liquid that consists of a mixture of triglycerides. The primary fatty acid components are oleic, linoleic, and pinolenic acids. Pinolenic acid is an isomer of gamma-linolenic acid with a variable concentration dependent on the source of the pine nut oil.2
Lipid Nutrition provides specifications for various fatty acids, including total oleic acid (≥ 22%), total linoleic acid (≥ 44%), and pinolenic acid (≥ 14%). Lipid Nutrition also provides specifications for maximum levels of contaminants. including heavy metals and microbes. Lipid Nutrition further provides results of three batch analyses of the Korean-pine nut oil that is the subject of the notice, indicating protein content below the limit of detection (0.3%) and unsaponifiable matter of approximately 0.7%.
Lipid Nutrition states that pine nuts are heated, crushed and pressed to give cold-pressed3 oil. This crude Korean-pine nut oil is heated, and caustic soda is then added to remove the free fatty acids. The resulting oil is then neutralized with a citric acid solution and stabilized with antioxidants. The stabilized oil is passed through a mixture of bleaching earth, activated carbon, and cellulose filters to remove impurities and to improve the physical characteristics of the oil. Finally, the oil is deodorized through steam stripping procedures, packaged into containers that minimize oxidation of the product, and stored under nitrogen. The notice provides information that processing aids and antioxidants used in the manufacture of the Korean-pine nut oil are used in compliance with the United States Code of Federal Regulations.
Using 2005-2006 National Health and Nutrition Examination Surveys, Lipid Nutrition estimates that dietary intake of Korean-pine nut oil would be 8.9 grams per person per day (g/p/d) at the mean and 17.8 g/p/d at the 90th percentile. Lipid Nutrition finds that 94.6% of the United States population would be consumers of Korean-pine nut oil.
Lipid Nutrition provides published information to support the safety of Korean-pine nut oil including absorption, distribution, metabolism and elimination (ADME) studies, a subchronic oral toxicity study, a reproductive study, and a genotoxicity study. Lipid Nutrition also includes a number of published human studies intended to corroborate the safety of Korean-pine nut oil.
Lipid Nutrition discusses published ADME studies that involve either pine nut oil4 or pinolenic acid, stating that the general ADME properties of pine nut oil are comparable to those of any triglyceride. These studies include a study in pregnant rats and several in vitro studies. Lipid Nutrition concludes that Korean-pine nut oil, including the pinolenic acid component, would be absorbed, distributed, metabolized and excreted in a similar fashion as other food oils.
Lipid Nutrition discusses a published 13-week oral toxicity study conducted in male and female rats to assess the effects of dietary administration of the Korean-pine nut oil that is the subject of this notice (containing 15.3% pinolenic acid) at up to 15% of the diet, resulting in exposures of up to 8.9 grams per kilogram of bodyweight per day (g/kg bw/d) for males and 10.2 g/kg bw/d for females, respectively. Lipid Nutrition reports that Korean-pine nut oil was well-tolerated by rats and no treatment-related signs of toxicity, abnormalities in functional observational tests, adverse findings in ophthalmologic examinations, body weight, food intake, hematology, macroscopic examination and histopathological evaluation occurred. Lipid Nutrition considers that the no observed adverse effect level is the highest amount tested; 8.9 and 10.2 g/kg bw/d for males and females, respectively.
Lipid Nutrition considers reproductive issues by means of the previously mentioned published study on pregnant rats fed maritime-pine nut oil. Lipid Nutrition notes that the authors of the rat study concluded that consumption of this pine nut oil had no adverse effects on maternal or fetal health, or the levels of omega-6 and omega-3 fatty acids in fetal rat brains.
In addition, Lipid Nutrition discusses the results of two published human studies involving short-term consumption of Korean-pine nut oil or its derivatives at up to 6 g. The notifier states that no serious adverse effects were observed and concludes that Korean-pine nut oil was well-tolerated.
Lipid Nutrition concludes that the published toxicological studies as well as other data and information support the safety and general recognition of Korean-pine nut oil under the intended conditions of use. Lipid Nutrition considers that this conclusion is corroborated by published human studies.
Standards of Identity
In the notice, Lipid Nutrition states its intention to use Korean-pine nut oil 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.
The Food Allergen Labeling and Consumer Protection Act of 2004 (FALCPA) amends the Federal Food, Drug, and Cosmetic Act (FFDCA) to require that the label of a food that is or contains an ingredient that bears or contains a “major food allergen” declare the presence of the allergen (section 403(w)). FALCPA defines a “major food allergen” as one of eight foods or food groups (i.e., milk, eggs, fish, Crustacean shellfish, tree nuts,5 peanuts, wheat, and soybeans) or a food ingredient that contains protein derived from one of those foods. Issues associated with labeling food are the responsibility of ONLDS.
Potential Labeling Issues
In describing the intended use of Korean-pine nut oil and the information that Lipid Nutrition relies on to conclude that Korean-pine nut oil is GRAS under the conditions of its intended use, Lipid Nutrition raises a potential labeling issue. Lipid Nutrition cites several human studies intended to test the ability of pinolenic acid to induce satiety. Under section 403(a) of the 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. under these labeling provisions of the FFDCA. If products that contain Korean-pine nut oil 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 Korean-pine nut oil on the label or in labeling.
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 Lipid Nutrition’s notice that Korean-pine nut oil is GRAS for its intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing Korean-pine nut oil. Accordingly, this response should not be construed to be a statement that foods that contain Korean-pine nut oil, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Lipid Nutrition, as well as other information available to FDA, the agency has no questions at this time regarding Lipid Nutrition’s conclusion that Korean-pine nut oil is 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 Korean-pine nut oil. As always, it is the continuing responsibility of Lipid Nutrition 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 000332, 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
1This CAS number is associated with pine nut oil from all Pinus species
2For example, pinolenic acid comprises approximately 15% of Korean-pine nut oil, but approximately 1% of oil obtained from the seeds of the Italian stone pine (Pinus pinea), another widely consumed pine nut oil.
3“Cold-pressed” refers to oil extraction without the use of solvents.
4From maritime-pine nut oil (Pinus pinaster), containing approximately 7% pinolenic acid.
5FDA discusses tree nuts in "Guidance for Industry: Questions and Answers Regarding Food Allergens, including the Food Allergen Labeling and Consumer Protection Act of 2004"; http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/FoodLabelingNutrition/ucm059116.htm. FDA's response to question 25 of this guidance states that pine nuts are considered "tree nuts" for the purposes of section 201(qq) of the FFDCA.