I1111111 111111 II 1111
`
`sR
`
`ORIGINAL SUBMISSION
`
`000003
`
`RIMFROST EXHIBIT 1048 page 0001
`
`

`

`k
`
`Specializing in FDA Regulatory Matters
`
`19-' 'i r:' 5 9 f<CV!)
`
`I),-
`
`May 26,2007
`
`Office of Food Additive Safety (HFS-255)
`Center for Food Safety and Applied Nutrition
`Food and Drug Administration
`5 100 Paint Branch Parkway
`College Park, MD 20740-3835
`
`RE:
`
`Notification of GRAS Determination for Krill-based Lecithin in Food
`
`Dear SidMadame:
`
`In accordance with proposed 21 CFR § 170.36 (Notice of a claim for exemption based on a
`GRAS determination) published in the Federal Register (62 FR 18939-18964), I am submitting
`in triplicate, as the agent to the notifier, Enzymotec, a GRAS Notification for krill-based lecithin
`under the conditions of its intended use in food.
`
`/. 1.
`
`Please let me know if you have any questions.
`
`Edward A. S&le
`President
`
`Enclosures
`
`EAS Consulting Group, LLC
`1940 Duke Street, Suite 200, Alexandria, Virginia 22314
`(877) 327-9808 Toll Free. (703) 684-4408 Local. (703) 684-4428 Fax
`
`000004
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`RIMFROST EXHIBIT 1048 page 0002
`
`

`

`Specializing in FDA Regulatory Matters
`
`By:-- ----____________
`
`I
`
`A.
`
`GRAS Exemption Claim
`
`Claim of Exemption From the Requirement for Premarket Approval Pursuant to
`Proposed 21 CFR §170.36(~)(1) 162 FR 18938 (17 April 1997)]
`
`Krill-based lecithin has been determined to be Generally Recognized As Safe (GRAS),
`consistent with Section 201(s) of the Federal Food, Drug, and Cosmetic Act. This determination
`is based on scientific procedures as described in the following sections, under the conditions of
`its intended use in food. Therefore, the use of krill-based lecithin in food, as described below, is
`exempt from the requirement of premarket approval.
`
`Signed,
`
`Agent for:
`
`Enzymotec, Ltd
`P.O. Box 6, Migdal HaEmeq
`Israel 23 106
`
`Krill-based lecithin GRAS notification
`
`1
`
`EAS Consulting Group, LLC
`1940 Duke Street, Suite 200, Alexandria, Virginia 22314
`
`(877) 327-9808 Toll Free. (703) 684-4408 Local - (703) 684-4428 Fax
`RIMFROST EXHIBIT 1048 page 0003
`
`000005
`-
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`

`B.
`
`Name and Address of Notifier
`
`Ms. Iris Meiri-Bendek
`Regulatory Affairs Manager
`Enzymotec, Ltd
`P.O. Box 6, Migdal HaEmeq
`Israel 23 106
`
`C.
`
`Common Name of the Notifi d Substance
`
`The substance is commonly known as lecithin. Commercial lecithin is a complex mixture
`obtained from edible food sources that is characterized by the principle component phosphatidyl
`choline. The composition of both the phosphatidyl choline and the lecithin mixture may vary
`depending on the source from which it is obtained, as described below. Because the fatty acid
`composition of marine-derived substances differs from that of plants in a way significant for
`nutrition, a unique name is appropriate. In this notice, we are describing the product as krill-
`based lecithin although we have described it in previous correspondence as marine-derived
`phosphatidyl choline, or MD-PC.
`
`,- L
`
`D.
`
`Conditions of Intended Use in Food
`
`The lecithin derived from krill is intended for use as a nutrient in those foods, at levels listed
`below in Table I, that do not contain other significant sources of docosahexaenoic acid (DHA)
`or eicosapentaenoic acid (EPA) as ingredients.
`
`Krill-based lecithin GRAS notification
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`RIMFROST EXHIBIT 1048 page 0004
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`

`I,
`
`Table I
`
`Food
`
`Breakfast bars
`
`YO Krill-based Lecithin
`
`3.8
`
`Dairy product analogs (soy products) 0.6
`
`Fat spreads
`
`Milk-based beverages
`
`Yogurt
`
`Soft candy
`
`10.0
`
`0.6
`
`0.7
`
`3.3
`
`E.
`Basis for the GRAS Determination
`Pursuant to 21 CFR 5 170.30, krill-based lecithin has been determined to be GRAS on the basis
`of scientific procedures.
`
`F.
`
`Availability of Information
`
`The data and information that serve as the basis for this GRAS Notification will be sent to the
`U.S. Food and Drug Administration (FDA) upon request, or will be available for review and
`copying at reasonable times at the offices of:
`
`Ms. Iris Meiri-Bendek
`Regulatory Affairs Manager
`Enzymotec, Ltd
`P.O. Box 6, Migdal HaEmeq
`Israel 23 106
`
`Krill-based lecithin GRAS notification
`
`L
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`3
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`RIMFROST EXHIBIT 1048 page 0005
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`

`

`Should the U.S. Food and Drug Administration (FDA) have any questions or additional
`information requests regarding this notification, Enzymotec, Ltd. will supply these data and
`information.
`
`11.
`
`Detailed Information About the Identity of the Substance
`
`A. Identity
`
`Chemical or common names
`
`Phosphatidylcholine
`
`1,2-diacyl-sn-glycero-3-phosphocholine
`
`Lecithin
`
`Structure of Phosphatidylcholine
`
`Phosphatidylcholine is a phospholipid that is a major constituent of cell membranes. More than
`90% of bile phospholipids are represented by phosphatidylcholine. Phosphatidylcholine is also
`known as, PtdCho and lecithin. It is represented by the chemical structure in Figure 1 :
`
`R nnd R' = fatty acids residues
`
`0
`
`Figure 1. Phosphatidylcholine
`
`The term lecithin itself has different meanings when used in chemistry and biochemistry than
`when used commercially. Chemically, lecithin is phosphatidylcholine. Commercially, the term
`lecithin refers to a natural mixture of neutral and polar lipids containing a large fraction of
`Krill-based lecithin GRAS notification
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`RIMFROST EXHIBIT 1048 page 0006
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`

`phosphatidylcholine. Lecithin is naturally consumed through a diet containing lecithin rich
`foods such as egg yolk, soybeans, grains, wheat germ, fish, legumes, yeast, and peanuts, to name
`a few examples.
`
`Phosphatidylcholine, which is a relatively polar lipid, is present in commercial lecithin at
`concentrations ranging from 20 to 90%. Soybean, sunflower and rapeseed are the major plant
`sources of commercial lecithin with soybeans as the most common source. Plant lecithins are
`GRAS (generally recognized as safe) for use in food with no limitation other than current good
`manufacturing practice (21 CFR 184.1400). The fatty acid substituents on R and R' positions of
`phosphatidylcholine from plant and animal sources differ. The R' second or middle carbon of
`the phospholipid molecule is mainly occupied by unsaturated fatty acids.
`
`Lecithin from krill is produced in two grades, A & B, differing in the purification level of the
`phosphatidylcholine. In lecithin derived from krill, the combined DHA (docosahexaenoic acid)
`and EPA (eicosapentaenoic acid) content is approximately 14-1 8% for Grade A and 20-25% for
`Grade B.
`
`Attached in Appendix A is a comparison of the Enzymotec krill-based lecithin products for both
`Grades A and B to the phospholipid content of commercial soy lecithin (Table A-1) and a
`comparison of the fatty acid content of commercial lecithin and menhaden oil to Grades A and B
`(Table A-2). As the comparison of soy- and krill-based lecithin products shows, the overall
`compositions are essentially the same except for the fatty acids, which reflect the different
`sources. The phospholipid composition shown in Table A-1 is very similar for the other two
`sources of lecithin. The fatty acid composition of Grades A and B is similar to that of menhaden
`oil and differs from soybean lecithin fatty acid composition in having notable amounts of the
`omega-3 fatty acids, particularly EPA and DHA, as expected.
`
`Product Specifications
`
`Table I1 - Krill-based lecithin specifications
`
`Parameter
`
`Grade A
`Specification
`
`Grade B
`Specification
`
`Total phospholipids (%w/w)
`
`pv (meqKd
`Moisture (YO)
`
`Lead, cadmium, mercury
`
`Krill-based lecithin GRAS notification
`
`40-50
`
`<5.0
`
`13.0
`
`4 p p m
`
`70-95
`
`<5.0
`
`<3.0
`
`< 1 ppm
`
`5
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`B. Method of Manufacture and Compositional Analysis
`
`The source for this lecithin will be krill, which are tiny, free-swimming, shrimp-like crustaceans
`(euphausiids), which exist in large numbers in the open sea, mainly near Antarctica. The raw
`material to be extracted, krill meal, is a biomass composed of lipids, sugars and proteins. By
`using a solvent extraction process, the proteins and free sugars are removed so that only lipids
`are left. Various solvents may be used for the extraction process, all of which are of food-grade
`quality and are used and removed from the product in accordance with current good
`manufacturing practice. The resulting extract, Krill-based lecithin Grade A may be further
`processed to enrich the phospholipid fraction and obtain Grade B (see Figure 2).
`Food grade antioxidants are added to the products in accordance with good manufacturing
`practice.
`
`Table B-1 contains compositional data of several batches per each grade. Grade A includes
`phospholipids, neutral lipids and other lipids (e.g. glycolipids), while Grade B includes almost
`exclusively phospholipids, almost no neutral lipids and about 8-10% of "other" lipids. The
`"Other lipids" were calculated through subtraction of the total phospholipids and total neutral
`lipids from the total lipids. As indicated by the toluene and hexane insoluble analyses, the
`product does not include protein or free sugars. Table B-2 provides the main fatty acid
`composition for total product Grades A and B, as % fatty acids of the product (by mass) and the
`fatty acid composition of the phospholipids and the phosphatidylcholine.
`
`/r L
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`L
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`Krill-based lecithin GRAS notification
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`RIMFROST EXHIBIT 1048 page 0008
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`

`

`Figure 2. Krill-based lecithin-Manufacturing Process Diagram
`
`Krill meal
`
`Extraction
`
`Purification
`
`*
`
`Grade A
`
`Phospholipid
`enrichment
`
`Purification
`
`Grade B 0
`
`Krill-based lecithin GRAS notification
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`RIMFROST EXHIBIT 1048 page 0009
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`

`

`C. Intended use
`
`Krill-based lecithin is intended for addition to a limited number of conventional foods as a
`nutritional ingredient. It is intended for the general population at the levels identified in Table I
`to dairy products (milk drinks and yogurt types), soy products, spreads, breakfast bars, and soft
`candy. We recognize that there are Standard of Identity requirements for some of these proposed
`foods and do not intend to refer to them by the commonly recognized names such as milk,
`chocolate or yogurt.
`
`D. Levels of Addition
`
`The maximum levels of addition as shown in Table I are calculated so as not to exceed the upper
`limit of 3 giday of DHA and EPA as outlined in the menhaden oil regulation. Use is limited to
`food groups already described in 21 CFR 184.1472 (with breakfast bars considered as a cereal
`substitute) where no other significant source of DHA or EPA is added. Thus, krill-based lecithin
`will not add any DHA or EPA to food above that which is already permitted.
`
`,>.
`
`L
`
`E. Safety Assessment of Lecithin from Krill
`
`It is well established and recognized that phosphatidylcholine (lecithin) from either plant or
`animal sources is handled the same metabolically. Lecithin is absorbed into the mucosal cells of
`the small intestine, mainly in the duodenum and upper jejunum, following digestion by the
`pancreatic enzyme phospholipase A2 (Arnesjo et al., 1969; Belleville and Clement, 1969), by
`which the fatty acids in the 2 position are hydrolyzed to form lysophosphatidylcholine
`(lysolecithin) (Nieuwenhuizen et al., 1974). Following absorption by the enterocytes,
`reacylation of lysolecithin takes place in these intestinal mucosal cells, reforming
`phosphatidylcholine, while the previously released fatty acids can be further used for triglyceride
`synthesis (Tso and Fujimoto, 1994). Phosphatidylcholine is then transported by the lymphatic
`system in the form of chylomicrons to the blood and metabolized by peripheral tissues. After the
`liver takes up the chylomicron remnants, the lipids are repackaged and secreted in the very low
`density lipoproteins (VLDL) (Ginsberg, 1998; Kang and Davis, 2000). Phosphatidylcholine is
`also incorporated into cell membranes, particularly in the lung. Phosphatidylcholine is also
`metabolized to choline, fatty acids and glycerol. The fatty acids and glycerol are either oxidized
`to produce energy or become involved in lipogenesis. Choline serves as a precursor of the
`neurotransmitter acetylcholine and serum choline levels have been shown to peak between 2 to 6
`hours after oral intake of phosphatidylcholine.
`
`i
`
`Krill-based lecithin GRAS notification
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`RIMFROST EXHIBIT 1048 page 0010
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`L
`
`One possible basis for the biological actions of phosphatidylcholine administered orally is that
`the fatty acid from the 2 position is being utilized for either (a) triglyceride synthesis during the
`course of lipid absorption in the small intestinal epithelial cells; (b) for the formation of
`phosphatidylcholine for membranes in the small intestinal epithelial cells; or (c) used by other
`organs in the body. The fatty acids of phosphatidylcholine are shuffled to suit the needs of the
`cell as they change over time, or as the phosphatidylcholine "parent molecule" is transported
`from tissue to tissue, cell to cell, or perhaps even from spot to spot within a membrane. Enzymes
`(hydrolases, acyltransferases) that remove or replace (re-esterify) fatty acids at position 2 of
`phosphatidylcholine are found in the intestinal epithelial cells, the hepatocytes, and other cells of
`the body. Phosphatidylcholine is also produced endogenously; for example, the liver secretes
`between 15-20 grams of phospholipids into the intestinal lumen and, of that, over 90% is
`phosphatidylcholine (Tso ef al, 1977).
`
`In summary, there is no reason to believe, given the metabolic sequelae described above, that the
`marine-derived phosphatidylcholine and associated lipids normally present in marine organisms
`would pose any different health hazards than plant oil-derived lecithins and lipids except,
`possibly, for differences in lipid content based on the marine origin or possible contaminants
`from such a source. The following will discuss the consequences of increased consumption of
`DHA and EPA resulting from krill-based lecithin, and the possible presence of source-based
`contaminants.
`
`Recognizing that FDA has supplied tables of concentrations of menhaden oil in various foods
`consistent with safe levels of DHA and EPA, comparison of EPA + DHA concentrations in those
`foods from menhaden oil and krill-based lecithin may be done directly. In doing so, we are
`using FDA's statement in the response letter to GRN 000109 that menhaden oil contains 8%
`DHA and 14% EPA. Enzymotec concludes that the addition of krill-based lecithin to a small
`group of foods, other than baby foods, is GRAS at a level of approximately 1.5 gram per serving,
`which translates into a concentration that can be compared to that of menhaden oil, as described
`in the menhaden oil regulation. These levels are displayed in Table 111. Because Enzymotec's
`lecithin is produced in two grades, and because Grade B has a higher concentration of DHA and
`EPA, we will use Grade B as an upper limit scenario. The average composition of DHA and
`EPA in Grade B lecithin is 7.5% and 14.7 Yo, respectively. Coincidentally, this total of 22.2 % is
`essentially the same as that given by FDA (22%) for menhaden oil. Thus, we will compare
`concentrations of krill-based lecithin in foods with that of menhaden oil (see Table 111). Grade A
`is approximately 16% DHA + EPA so that will produce less DHA and EPA in the diet when
`added at 1.5 giserving. Serving sizes are taken from reference amounts in 21 CFR 101.12.
`
`Krill-based lecithin GRAS notification
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`RIMFROST EXHIBIT 1048 page 0011
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`

`

`,... -.---___^
`
`"
`
`I__^--
`
`_-
`
`Table 111
`
`Concentrations of Krill-based Lecithin and Menhaden Oil as stated in 21 CFR 184.1472
`
`Food
`
`Reference amount (21
`CFR 101.12)
`
`% Krill-based
`lecithin
`
`% Menhaden
`Oil
`
`Breakfast bars
`
`40 g
`
`Dairy product analogs (soy Not listed; milk-based
`products)
`drinks = 240 g
`
`Fat spreads
`
`15 ml; -15 g
`
`Milk-based beverages
`
`240 g
`
`Yogurt
`
`b L
`
`Soft candy
`
`225 g
`
`45 g
`
`3.8
`
`0.6
`
`10.0
`
`0.6
`
`0.7
`
`3.3
`
`5.0
`
`Fats and oils
`12.0
`
`Milk products
`5.0
`
`Milk Products
`5.0
`
`4.0
`
`The menhaden oil rule permits several additional applications where krill-based lecithin would
`not be used. The important point is that in all applications where either lecithin or menhaden oil
`might be used, the levels of lecithin (and subsequent levels of DHA+EPA) are lower than what is
`allowed from menhaden oil, sometimes much less. We agree with the limitation that krill-based
`lecithin not be used with other ingredients that are good sources of DHA or EPA; thus it will not
`be added to foods containing other significant sources of DHA or EPA as ingredients. The one
`food category discussed for krill-based lecithin that is not the subject of the menhaden oil rule is
`breakfast bars. However, these would generally substitute for cereals, which are allowed by the
`menhaden oil rule. According to 21 CFR 101.12, reference amounts for cereals range from 15 -
`55 g. At a concentration of menhaden oil of 4.0%, this would range from 0.6 to 2.2 g menhaden
`oil. Therefore, the use of krill-based lecithin in breakfast bars would simply substitute for
`breakfast cereals at a level lower than that allowed for menhaden oil. We also note that dairy
`product analogs (soy products) can come in a variety of forms such as "soy milk" or yogurt
`substitute. The important thing is that these would replace milk-based products already
`permitted in 184.1472.
`
`In sum, the use of krill-based lecithin in foods, as intended by Enzymotec, would contribute far
`less DHA + EPA than what is currently authorized from use of menhaden oil in these foods, as
`Krill-based lecithin GRAS notification
`10
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`RIMFROST EXHIBIT 1048 page 0012
`
`

`

`b
`
`listed in 184.1472, or other fish oils subject to GRAS notifications. Importantly, it does not
`contribute to any increase in cumulative DHA + EPA intake because krill-based lecithin would
`simply provide equal or less of these fatty acids than that which has already been considered for
`these foods and concluded to be safe. While use may broaden the range of products with these
`fatty acids from which a consumer may choose, such products would simply provide alternative
`products to those that are currently permitted and would not add to the current cumulative intake
`for users of such products.
`
`A second consideration is whether contaminants that might be stored in marine lipids could pose
`a risk to health. Krill have been a significant food for higher marine species and have presented
`no safety concern. Importantly, krill are very low on the food chain and would not
`bioaccumulate lipid-soluble contaminants as occurs in larger species. Nevertheless, because this
`ingredient is from the lipid fraction, we have conducted analyses for likely contaminants on two
`batches as found in Table C-1 in Appendix C. Because Grade B is made from Grade A, a simple
`calculation was performed using the exaggerated assumption that all of each contaminant would
`stay with the lecithin throughout the purification step and, thus, be concentrated by 2.5 times in
`the Grade B as compared to Grade A. This, of course, is unlikely but provides an upper-bound
`estimate. As seen, the levels are low and consistent with levels in other food ingredients.
`
`111’ L
`
`Finally, krill, being a crustacean, could contain protein that might be allergenic to individuals
`allergic to certain crustaceans. However, the processing of the lipid fraction should reduce
`proteins to a negligible level. Nevertheless, based on the requirements of the Food Allergen
`Labeling and Consumer Protection Act of 2004, the word “krill” will appear in the ingredient list
`unless it can be shown that no protein is present; a successful notification is filed demonstrating
`no allergenic protein; or a successful petition is filed demonstrating that the ingredient does not
`cause an allergic response that could pose a risk to human health.
`
`111. CONCLUSIONS
`
`In sum, based on the information provided above and the fact that the constituents of krill-based
`lecithin are commonly found in food, and because these lipids and phospholipids are essentially
`the same, and will be handled metabolically the same as those derived from plants, we conclude
`that scientific experts, generally, would recognize them to be as safe and as acceptable as plant
`lecithin and lipids. Further, we believe that there are no significant questions regarding the
`safety of krill-based lecithin that would appear to require additional safety studies, due to the
`prior consideration and acceptability by the Agency for plant-derived lecithin and other
`phospholipids and fish oil-derived omega-3 fatty acids.
`
`Krill-based lecithin GRAS notification
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`References
`
`Arnesjo B, Nilsson A, Barrowman J, Borgstrom B (1969) Intestinal digestion and absorption of
`cholesterol and lecithin in the human: Intubation studies with a fat-soluble reference substance.
`Scand J Gastroenterol. 4(8):653-665.
`
`Belleville J and Clement J (1960) Phospholipase A 2 activity of extracts of pancreatic juice and
`pancreas from humans, rats and dogs. JPhysiol (Paris). 61 Suppl 1 :87.
`
`Ginsberg HN (1998) Lipoprotein physiology. Endocrinol Metab Clin North Am. 27(3):503-5 19
`
`Kang S and Davis RA. (2000) Cholesterol and hepatic lipoprotein assembly and secretion.
`Biochim Biophys Acta. 1529(1-3):223-230.
`
`NAS IOM (National Academy of Sciences, Institute of Medicine) (1998) Dietary Reference
`Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin BI2, Pantothenic Acid,
`Biotin, and Choline. National Academies of Science Press, Washington, D.C.
`
`Nieuwenhuizen W, Kunze H, de Haas GH (1974) Phospholipase A2 bhosphatide acylhydrolase,
`EC 3.1.1.4) from porcine pancreas. Methods Enzymol. 32(Part B): 147- 154.
`
`I- L
`
`T S ~ P, B a h t JA, Simmonds WJ (1977) Role of biliary lecithin in lymphatic transport of fat.
`Gastroenterology. 73(6): 1362-1 367.
`
`Tso P and Fujimoto K. (1991) The absorption and transport of lipids by the small intestine. Brain
`Res Bull. 27(3-4):477-482.
`
`Krill-based lecithin GRAS notification
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`RIMFROST EXHIBIT 1048 page 0014
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`Appendix A:
`
`Typical phospholipid and fatty acid compositions of various lecithins
`
`Table A-1- Phospholipid composition
`
`Phospholipids
`Composition (“/w/w)
`
`Commercial
`fluid soy
`lecithin
`
`Grade B
`Grade A
`Commercial
`High Grade Soy Krill- based Krill- based
`Lecithin
`Lecithin
`Lecithin
`
`Total
`Phosphatidylcholine
`Phosphatidylethanolamine
`
`Phosphatidylinositol
`
`Lysophosphatidylcholine
`Others
`
`44
`35
`3
`1
`3
`2
`
`88
`78
`4
`0.5
`2.5
`3
`
`46
`36
`3
`2
`
`2
`3
`
`75-95
`60-85
`0-7
`1-5
`3-9
`1-6
`
`It,
`
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`RIMFROST EXHIBIT 1048 page 0015
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`

`

`Menhaden
`Oil*
`
`Grade A**
`Krill-based
`Lecithin
`
`Grade B**
`Krill-based
`Lecithin
`
`5.3
`
`7.5
`
`10.3
`
`14.7
`
`L
`
`Table A-2 - Fatty acid composition
`Fatty Acid
`Soybean
`Composition
`Lecithin*
`as % wlw of
`product
`22:6n3 (DHA)
`22:5n3
`22: 1
`205113 (EPA)
`20:4
`20: 1
`C18:4
`C18:3
`C18:2
`C18:l
`
`0.00
`0.00
`0.00
`0.00
`0.00
`0.00
`0.00
`5.14
`40.18
`10.57
`
`8.56
`4.92
`0.35
`13.17
`1.17
`1.33
`2.74
`1.49
`2.15
`14.53
`
`0.9
`
`1.5
`13.2
`
`0.8
`
`2.3
`5.8
`
`0.7
`1.2
`13.0
`1.2
`
`0'
`
`L
`
`0.9
`3.78
`2.92
`C18:O
`5.2
`10.48
`0.40
`C16:l
`15.1
`15.15
`11.98
`C16:O
`7.1
`7.96
`0.10
`C14:O
`* Source - The USDA National Nutrient Database for Standard Reference
`** Average fatty acid composition of main fatty acids
`
`Krill-based lecithin GRAS notification
`
`14
`000018
`RIMFROST EXHIBIT 1048 page 0016
`
`

`

`L
`
`Appendix B: Krill-based Lecithin -Batch data
`
`Table B-1 -Product composition
`
`Grade A
`
`Batch
`---------
`
`.
`
`44.2
`
`Lipid composition
`Total
`
`Phospholipids
`(%W/W)
`
`Phosphatidyl
`choline (PC)
`Phosphatidyl
`ethanolamine (PE)
`Phosphatidylinosito 0.8
`1 (PI)
`Lysophosphatidyl
`choline (LPC)
`Others
`
`36.8
`
`1.5
`
`2.8
`
`2.3
`
`Grade B
`
`Batch
`-----------
`
`Batch
`-----------
`
`Batch
`---------
`
`Batch
`----------
`
`Batch
`----------
`
`45.4
`
`37.3
`
`2.1
`
`1.4
`
`2.8
`
`1.9
`
`47.3
`
`33.7
`
`4.2
`
`2.1
`
`1.1
`
`6.3
`
`91.8
`
`82.5
`
`0.0
`
`1.9
`
`6.4
`
`1.1
`
`75.6
`
`60.2
`
`2.1
`
`1.9
`
`8.1
`
`3.4
`
`89.2
`
`65.1
`
`6.8
`
`4.1
`
`3.3
`
`5.3
`
`L
`
`Total
`
`52.0
`
`50.0
`
`47.3
`
`Neutral lipids
`(%W/W)
`
`Other lipids (e&
`glycolipids)
`(%W/W) *
`Toluene insoluble
`
`Hexane insoluble
`
`Diglycerides
`
`19.8
`
`13.0
`
`Monoglycerides
`
`Triglycerides
`
`Free fatty acids
`
`Free cholesterol
`
`Cholesterol esters
`
`2.0
`25.3
`
`2.9
`
`ND
`
`2.0
`
`3.8
`
`4.9
`
`25.3
`
`3.8
`
`1
`
`2.1
`
`4.5
`
`13.6
`
`2.2
`
`25.6
`
`3.2
`
`1.4
`
`1.4
`
`5.3
`
`ND
`
`ND
`
`ND
`
`ND
`
`ND
`
`ND
`
`8.0
`
`None
`
`None
`
`None
`
`None
`
`None
`
`None
`
`* calculated based on mass balance
`
`k*
`
`Krill-based lecithin GRAS notlficatlon
`
`ND
`
`ND
`
`ND
`
`0.8
`
`ND
`
`ND
`
`10.0
`
`15
`
`OOOQ19
`RIMFROST EXHIBIT 1048 page 0017
`
`

`

`L
`
`Appendix B continued: Krill Lecithin - batch data
`Table B-2 - fatty acid profile
`
`Fatty acid profile (main fatty acids)
`As %w/w of the oroduct
`DHA
`EPA
`C18:4 n3
`C18:2
`C18:l
`C18:O
`C16:l
`C16:O
`C14:O
`
`As % oftotal fatty acids on Phosoholipids
`
`,- - L
`
`DHA
`EPA
`C18:4 n3
`C 18:2
`C18:l
`C18:O
`C16:I
`C16:O
`C14:O
`
`Grade A
`
`Grade B
`
`Batch
`---------
`.
`
`Batch
`-----------
`.
`
`Batch
`162-29A
`
`Batch
`---------
`.
`
`Batch
`-----------
`.
`
`.
`
`Batch
`----------
`
`5.2
`10.7
`I .2
`1.1
`12.9
`0.8
`5.3
`14.4
`6.8
`
`14.0
`
`28.5
`1.8
`6.0
`7.0
`1.3
`2.5
`25.0
`2.2
`
`4.9
`9.7
`0.8
`1.3
`13.5
`0.9
`5.5
`16.1
`8.2
`
`14.7
`25.9
`1.4
`5.7
`13.5
`1.3
`1.7
`22.8
`1.5
`
`5.8
`10.4
`0.6
`2.2
`13.1
`0.9
`4.8
`14.7
`6.3
`
`15.8
`26.4
`1.3
`5.7
`14.1
`1.5
`1.6
`22.5
`1.5
`
`6.7
`15.4
`1 .o
`2.5
`3.4
`0.5
`1.1
`13.2
`
`1.2
`
`13.3
`30.5
`2.0
`5.8
`6.7
`1 .o
`2.1
`26.0
`2.2
`
`6.5
`13.6
`0.7
`1.1
`5.9
`0.8
`1.3
`12.0
`1.4
`
`11.2
`25.4
`1.4
`2.2
`12.2
`1.3
`2.2
`26.2
`2.3
`
`9.2
`15.2
`0.7
`3.3
`8.0
`0.8
`1.1
`13.8
`1.1
`
`12.2
`23.0
`1.4
`6.2
`14.8
`1.5
`1.9
`25.6
`1.9
`
`Krill-based lecithin GRAS notification
`
`16
`
`000020
`RIMFROST EXHIBIT 1048 page 0018
`
`

`

`As % of total fattv acids on PC
`
`DHA
`EPA
`C 18:4 n3
`C18:2
`C18:l
`C18:O
`C16:l
`C16:O
`
`C14:O
`
`Grade A
`
`Grade B
`
`Batch
`---------
`.
`
`.
`
`Batch
`----------
`
`Batch
`----------
`.
`
`.
`
`Batch
`--------
`
`Batch
`----------
`
`Batch
`----------
`
`.
`
`.
`
`13.2
`31.6
`1.7
`5.3
`6.8
`1 .o
`2.0
`24.0
`
`1.7
`
`11.7
`27.9
`1.6
`2.9
`13.0
`
`1.3
`1.9
`23.0
`1 .o
`
`13.5
`32.1
`0.3
`1.1
`13.5
`
`1.0
`1.8
`22.9
`
`1.5
`
`12.5
`30.6
`1.9
`5.2
`6.8
`
`1 .O
`2.1
`25.0
`
`1.9
`
`13.7
`12.0
`31.2
`27.7
`0 3
`1.5
`1.3
`2.2
`11.3 12.9
`
`1.1
`2.3
`25.6
`
`2.4
`
`1.2
`1.7
`22.2
`
`1.2
`
`L-
`
`Krill-based lecithin GRAS nottficatlon
`
`17
`
`000021
`RIMFROST EXHIBIT 1048 page 0019
`
`

`

`Appendix C: Chemical contaminants
`
`L
`
`Table C-1
`
`PCBs - Total
`
`PCBs -sum of
`28,52,101,118,138,153,180
`Dioxins and Furans
`WHO TEQ with DLs
`Pesticides
`
`Heavy metals
`
`Total Arsenic
`
`Inorganic Arsenic
`
`Grade A
`
`Batch
`---------
`8.5 ppb
`
`.
`
`1.5 ppb
`
`1.6 ppt
`
`Grade B (calculated
`values*)
`Batch
`---------
`.
`121.3 ppb
`
`Batch
`----------
`.
`15.4 ppb
`
`Batch
`----------
`.
`2.1 ppb
`
`0.3 ppb
`
`53.7 ppb
`
`10.7 ppb
`
`0.5 ppt
`
`53.9 ppt
`
`51.3 ppt
`
`Non
`detect e d
`
`Non
`detected
`
`3.6 ppm
`
`3.6 ppm
`
`- <9.0 ppm
`
`59.0 ppm
`
`<0.005ppm Not
`measured
`<0.05 ppm
`
`<0.05 ppm
`
`<0.0125
`ppm
`<0.125 ppm
`
`<0.005ppm
`
`0.009ppm
`
`*-
`L
`
`Lead
`
`Mercury
`
`<0.125
`PPm
`- <0.0225
`<0.0125
`PPm
`PPm
`10.125
`<0.125 ppm
`<0.05 ppm
`10.05 ppm
`Cadmium
`PPm
`* Grade B is a 2.5 fold concentrate of Grade A, thus the worse case scenario for contaminants
`would be that all of them are carried over to Grade B and therefore the levels in Grade A would
`be multiplied by 2.5.
`
`L
`
`Krill-based lecithin GRAS notification
`
`000022
`
`18
`
`RIMFROST EXHIBIT 1048 page 0020
`
`

`

`Batch --------- -Dioxins and Furans
`.
`
`345 S o u ~ a l e Drive
`Guslph ON N I G 3M5 CANADA
`Tel 519-822-2438
`Fax 519-822-2849
`
`2006481.ENZ
`
`I
`Table A: Dioxms and Funns. Oil Ippt)
`
`I 1
`I
`1
`
`I
`
`1
`
`
`
`/" i
`
`123467BHpCDF
`1234789-HpCDF
`Total HpCDFa
`
`i
`
`,
`
`~
`
`0 2
`ND(O1)
`0 2
`
`I
`1
`1 1 1
`
`1 1
`NDRiO3)
`2 2
`
`
`
`I
`
`I
`I
`1 2 1
`
`I
`I
`
`I
`I
`
`I
`
`123478-HXCdD:. .,
`123878-HxCDD
`12378PHxCDO
`I",. * r n n .
`
`123467BHpCDD
`Total HpCDDs
`
`i
`
`I
`
`..l ," .,
`
`0 3
`0 3
`
`,
`i
`
`,
`
`I
`I NDR(22)
`1 1 1
`1 5
`
`. - . . -
`
`
`
`i
`l
`I
`1
`1 1 1
`
`I
`
`I
`
`Page 1
`
`Krill-oasea iecirnin b ~
`
`noriricarion
`~ b
`
`000023
`
`I Y
`
`RIMFROST EXHIBIT 1048 page 0021
`
`

`

`345 Swlhgate Drive
`Guelph ON N1G 3M5 CANADA
`TeI 519-822-2438
`Fax 519-822-2848
`
`7 e
`
`Page 2
`
`Krill-based lecithin GRAS notification
`
`20
`
`000024
`RIMFROST EXHIBIT 1048 page 0022
`
`

`

`Batch --------- - PCBs
`.
`
`L.
`
`Krill-based lecithin GRAS notification
`
`21
`
`000025
`RIMFROST EXHIBIT 1048 page 0023
`
`

`

`L
`
`Krill-based lecithin GRAS notification
`
`22
`
`000026
`RIMFROST EXHIBIT 1048 page 0024
`
`

`

`Batch 80-63A -Pesticides
`
`WELLINGTON
`L A B O R A T O P I E S
`
`345 Southgale Onw
`GUelph ON N1G 3M5 CAN&DA
`Tal 5194224436
`Fax 519-322-2849
`
`Page 1
`
`Krill-based lecithin GRAS notification
`
`23
`
`000827
`RIMFROST EXHIBIT 1048 page 0025
`
`

`

`Batch ---------- -Dioxins and Furans
`.
`
`345 S0"vgSlS hive
`Guelph ON N1G 3M5 CANADA
`Tel 519-822-2436
`Fax 519-822-2849
`
`I
`
`I
`
`Page 1
`
`\k
`
`Krill-based lecithin GRAS notification
`
`24
`
`000028
`RIMFROST EXHIBIT 1048 page 0026
`
`

`

`345 Southgale D m
`Guelph ON N I G 3M5 CANADA
`Tsl 51W22-2436
`Fax 519-822-2849
`
`r L
`
`I '
`
`I
`
`I
`
`I
`
`
`
`I
`
`Page 2
`
`I,
`
`Krill-based lecithin GRAS notification
`
`25
`000029
`
`RIMFROST EXHIBIT 1048 page 0027
`
`

`

`Batch ---------- - PCBs
`.
`
`i
`
`Kriii-Dasea iecitnin ~ K P . > noiiricaIion
`
`RIMFROST EXHIBIT 1048 page 0028
`
`

`

`I,
`
`Krill-based lecithin GRAS notification
`
`27
`000031
`RIMFROST EXHIBIT 1048 page 0029
`
`

`

`- , -
`
`..
`. .
`
`. .
`
`Batch ---------- - Pesticides
`.
`
`k
`
`2006-643-ENZ
`-~
`... .
`Table C : Oramochlorine Pesticide* In Oil lnda or PPBL
`
`~~
`
`I
`
`QRGANOCHLORINE
`
`I
`
`1
`I
`
`~~ Lab Blaw
`
`NO(2)
`
`345 Southgate Drive
`GuelphQN N1G 3M5CANADA
`Tel 519822-2436
`FBX 519-822-2848
`
`..
`
`__
`...
`162-29D
`
`NO(3)
`
`I
`
`L
`
`Krill-based lecithin GRAS notification
`
`28
`
`Page 1
`
`000032
`RIMFROST EXHIBIT 1048 page 0030
`
`

`

`SUBMISSION END
`
`000033
`
`RIMFROST EXHIBIT 1048 page 0031
`
`