Agency Response Letter
GRAS Notice No. GRN 000123

Michael Russell
Chief Operating Officer
Fuji Foods, Inc.
6206 Corporate Park Drive
Browns Summit, NC 27214

Re: GRAS Notice No. GRN 000123

Dear Mr. Russell:

The Food and Drug Administration (FDA) is responding to the notice, dated January 14, 2003, 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 January 22, 2003, filed it on January 28, 2003, and designated it as GRAS Notice No. GRN 000123.

The subject of the notice is Laminaria japonica extract, prepared by the extraction of dehydrated L. japonica leaves with water. The notice informs FDA of the view of Fuji Foods Inc. (Fuji) that L. japonica extract is GRAS, through scientific procedures, for use as a flavor enhancer or flavoring agent in marinades, soups, gravies, and seasonings. The maximum amount of L. japonica extract in the final food product would be 0.08 percent, regardless of whether L. japonica extract is added directly to food or added to marinades and gravies that are subsequently applied to food; above this concentration, some foods acquire an undesirable taste.

Because L. japonica is a type of seaweed, Fuji describes generally available information about consumption of seaweed and seaweed-derived products. Seaweed is a common food in Japan, where it is consumed as a vegetable, made into tea, or present as an ingredient in foods such as soups, noodles, salads, cakes, jellies, and sauces. The mean intake of seaweed in the Japanese diet has been reported to be approximately 7 grams per person per day (g/p/d). Seaweed species that are commonly consumed in Japan include red algae such as nori (Porphyra spp.) and brown algae such as kombu (Laminaria spp.) and wakame (Undaria spp.). Fuji also describes generally available information about "kelp," which is a general term that refers to brown algae, including Laminaria spp. and Macrocystis spp. Fuji describes seaweed-derived products such as alginates, which are polysaccharides that are isolated from brown algae and added as thickening agents to foods.

L. japonica is a brown algae that is the primary species of seaweed consumed in Japan and is ranked number one worldwide by production volume of aquaculture products. L. japonica is prevalent in the cold waters of the North Atlantic and Pacific oceans. With the exception of the root, the entire plant is used as a whole food or as a source of food ingredients. FDA has affirmed that brown algae (including dried and ground or chopped L. japonica) is GRAS for use in spices, seasonings, and flavorings as a flavor enhancer or flavor adjuvant (21 CFR 184.1120).

Fuji describes the general composition of kelp reported in the literature. Kelp dry matter contains approximately 8 percent protein, 8 percent crude fiber, 55 percent carbohydrate, and 27 percent minerals. The carbohydrates in kelp include polysaccharides such as alginates, lamanarins, and fucoidans. Fuji also cites published values for the chemical composition of L. japonica, including the volatile chemical components of L. japonica. Fuji notes that L. japonica essential oil, which is a mixture of aroma compounds obtained by distillation, contains predominantly cubenol (sesquiterpene alcohol), myristic acid, and palmitic acid and that the sesquiterpene alcohol is an important contributor to kelp flavor.

Fuji describes the manufacture of two product forms of L. japonica extract - i.e., a liquid form and a powder form. To prepare the liquid form, dehydrated L. japonica is soaked in water for a minimum of 16 hours, and then briefly heated to 190 degrees F. The liquid extract is drained, filtered and centrifuged, and then heated to 185 degrees F for at least 5 minutes. Salt is added if needed to adjust the salt content to specification (13 - 14 percent) and the L. japonica leaves are discarded. The resulting liquid extract may be used as such or made into a powder by spray drying the extract with a carrier such as maltodextrin.

Fuji reports the chemical composition of liquid L. japonica extract, which contains 39 percent dissolved solids and 61 percent water. The solid material includes salt, free amino acids, carbohydrates, and minerals. Fuji presents the amino acid composition of L. japonica extract in detail and notes that the predominant amino acids are glutamic acid and aspartic acid. Fuji notes that the component of L. japonica extract that is primarily responsible for the flavor enhancing property of the extract is the sodium salt of glutamic acid (i.e. monosodium glutamate). Fuji reports the mineral composition of the extract, which contains sodium, potassium, calcium, magnesium, iron, zinc, and iodine. Fuji also provides specifications for L. japonica extract, including a specification for the iodine content (less than or equal to approximately 1600 milligrams iodine per kilogram of extract). Fuji estimates that intake of L. japonica extract from its proposed uses would be approximately 150 milligrams per person per day (mg/p/d) at the 90th percentile⁽¹⁾ and states that the use of L. japonica extract as a flavor enhancer or flavoring agent is self-limiting.

Fuji discusses generally available reports and studies relevant to the safety of L. japonica extract. Fuji cites a 1973 report by the Select Committee on GRAS Substances⁽²⁾ regarding the safety of brown algae and red algae as food ingredients. The committee concluded that there was no substantive evidence or reason to suspect a significant risk to public health from use of these ingredients as spices, seasonings, and flavorings. Fuji notes that standard toxicity studies are not found in the literature because L. japonica has a history of consumption as food, but that some studies have been conducted to evaluate potential beneficial effects of L. japonica. In this regard, Fuji describes the results of human clinical and epidemiological studies and of in vitro and animal studies that have evaluated various effects of L. japonica and other Laminaria species or their extracts.

Fuji acknowledges that excessive iodine consumption can have adverse effects at high levels but notes that such effects appear to be reversible. Based on its estimate that intake of L. japonica extract at the 90th percentile would be approximately 150 mg/p/d, and its specification that the iodine content of L. japonica extract is less than or equal to approximately 1600 milligrams iodine per kilogram of extract, Fuji estimates that intake of iodine from the consumption of L. japonica extract would be approximately 240 micrograms/p/d⁽³⁾ and notes that this intake is several-fold less than the intake that has been associated with adverse effects of iodine. Fuji also notes that FDA has approved the addition of kelp to food as a source of iodine, provided that the maximum intake of the food as may be consumed during a period of one day does not result in daily ingestion of kelp so as to provide a total amount of iodine in excess of 225 micrograms (21 CFR 172.365).

As part of its notice, Fuji includes the report of a panel of individuals (Fuji's GRAS panel) who evaluated the data and information that are the basis for Fuji's GRAS determination. Fuji considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Fuji's GRAS panel evaluated dietary exposure, identity of kelp source material, method of production, and product specifications. Fuji's GRAS panel reviewed the reported history of use of L. japonica as a foodstuff in the United States and Japan, as well as data and information from human and in vitro studies. Fuji's GRAS panel concluded that L. japonica extract, meeting food grade specifications, is GRAS for its intended use.

Potential Labeling Issues

Section 403(a) of the Federal Food, Drug and Cosmetic Act (FFDCA) provides that a food shall be deemed to be misbranded if its labeling is false or misleading in any particular. Section 403(r) of the FFDCA lays out the statutory framework for health claims. In describing information that the notifier relies on to conclude that L. japonica extract is GRAS under the conditions of its intended use, Fuji raises issues under these labeling provisions of the FFDCA. These issues include Fuji's description of animal studies suggesting that seaweeds and seaweed extracts may have beneficial effects. These issues are the purview of the Office of Nutritional Products, Labeling and Dietary Supplements (ONPLDS) in the Center for Food Safety and Applied Nutrition. The Office of Food Additive Safety neither consulted with ONPLDS on these labeling issues nor evaluated the information in Fuji's notice to determine whether it would support any claims made about L. japonica extract on the label or in labeling.

Use in Meat and Poultry Products

The intended use of L. japonica extract in products such as marinades, soups, gravies, and seasonings will result in the presence of L. japonica extract in meat and poultry products. Therefore, during its evaluation of GRN 000123, OFAS consulted with the Labeling and Consumer Protection Staff of the Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture (USDA). Under the Federal Meat Inspection Act and the Poultry Products Inspection Act, FSIS is responsible for determining the efficacy and suitability of food ingredients in meat and poultry products as well as prescribing safe conditions of use. Suitability relates to the effectiveness of the ingredient in performing the intended purpose of use and the assurance that the conditions of use will not result in an adulterated product, or one that misleads consumers.

FSIS had no objection to the use of L. japonica extract (identified as such on labeling) as a flavor enhancer and flavoring agent in marinades for meat and poultry, meat and poultry soups, gravies, and seasonings at a level not to exceed 0.08 percent by weight. FSIS notes that the addition of salt to the extract would require ingredient labeling.

Conclusions

Based on the information provided by Fuji, as well as the information in GRN 000123 and other information available to FDA, the agency has no questions at this time regarding Fuji's conclusion that L. japonica extract 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 L. japonica extract As always, it is the continuing responsibility of Fuji 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, as well as a copy of the information in your notice that conforms to the information in proposed 21 CFR 170.36(c)(1), is available for public review and copying on the homepage of the Office of Food Additive Safety (on the Internet at http://www.cfsan.fda.gov/~lrd/foodadd.html).

Sincerely,    /s/ Laura M. Tarantino, Ph.D. Acting Director Office of Food Additive Safety Center for Food Safety      and Applied Nutrition

cc: Dr. Robert Post, Director
Labeling and Consumer Protection Staff
Office of Policy, Program Development and Evaluation
Food Safety and Inspection Service
1400 Independence Ave., SW, Suite 602, Annex
Washington, DC 20250-3700

References

1. Pennington, J.A.T., S.A. Schoen, G.D. Salmon, B. Young, R.D. Johnson, and R.W. Marts, 1995. Composition of core foods in the U.S. food supply, 1982-1991. Journal of Food Composition and Analysis 8:171-217.

2. "Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickle, Silicon, Vanadium, and Zinc" (2002) Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Available online at http://www.nap.edu.

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⁽¹⁾Based on Fuji's proposed conditions of use, FDA made an independent estimate that intake of L. japonica extract would be approximately 300 mg/p/d at the 90th percentile. FDA's estimate of exposure is based on the conservative assumptions that L. japonica extract is added at the maximum use level to all soups and marinades, and that all soups and marinades would contain the extract.

⁽²⁾Several years ago, FDA contracted with the Life Sciences Research Office (LSRO) of the Federation of American Societies for Experimental Biology as part of its comprehensive review of GRAS and prior sanctioned food ingredients. To aid in that review, LSRO established the Select Committee on GRAS Substances.

⁽³⁾Based on its independent estimate of intake of L. japonica extract, FDA estimated that the concomitant intake of iodine at the 90th percentile would be approximately 460 micrograms/p/d. FDA notes that the 90th percentile value for the usual intake of iodine from food (including added or naturally-occurring iodine) also is 460 micrograms/p/d, based in part on FDA's Total Diet Study (Ref. 1) as described by the National Academy of Sciences (Ref. 2). If iodine exposure from the use of L. japonica extract is conservatively assumed to be in addition to the background dietary intake of iodine, the resultant intake approaches, but does not exceed, the tolerable upper limit of intake of iodine for adults of 1100 micrograms/p/d as described by the National Academy of Sciences (Ref. 2). (By definition, the tolerable upper limit represents the highest level of daily intake of iodine that is likely to pose no risk of adverse health effects in almost all individuals.)