U. S. Food and Drug Administration
Center for Food Safety and Applied Nutrition
Office of Food Additive Safety
December 20, 2002

Claire L. Kruger, Ph.D., D.A.B.T.
Environ Corporation
4350 North Fairfax Drive
Suite 300
Arlington, VA 22203

Re: GRAS Notice No. GRN 000108

Dr. Kruger:

The Food and Drug Administration (FDA) is responding to the notice, dated June 21, 2002, that you submitted on behalf of T&R Chemicals, Inc. (T&R) 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 June 26, 2002, filed it on June 28, 2002, and designated it as GRAS Notice No. GRN 000108.

The subject of the notice is glycerol ester of gum rosin. The notice informs FDA of the view of T&R that glycerol ester of gum rosin is GRAS, through scientific procedures, for use in citrus oils that are added to beverages to increase the density of the citrus oil and to act as an emulsifier at a maximum level of 100 parts per million. T&R estimates that the intake of glycerol ester of gum rosin would be 43 milligrams per person per day (mg/p/d) at the mean and 75 mg/p/d at the 90th percentile.

FDA has evaluated the information that T&R discusses in its GRAS notice as well as other data and information that are available to the agency. As discussed more fully below, the notice does not provide a sufficient basis for a determination that glycerol ester of gum rosin is GRAS under the conditions of its intended use.

Data and information that T&R presents to support its GRAS determination

In evaluating whether the intended use of glycerol ester of gum rosin is GRAS, T&R presents its view that glycerol ester of gum rosin is toxicologically and chemically equivalent to glycerol ester of wood rosin. For clarity in distinguishing between these two substances, in this letter FDA refers to glycerol ester of gum rosin as "gum rosin ester" and to glycerol ester of wood rosin as "wood rosin ester."

T&R provides the report of a panel of individuals (T&R's GRAS panel) who evaluated the data and information that are the basis for T&R's GRAS determination. T&R considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. T&R's GRAS Panel concluded that no evidence exists in the available information on gum rosin ester that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when gum rosin ester is used at levels that are now current or that might reasonably be expected from its proposed use.

T&R notes that FDA has approved the following food additive uses of gum rosin ester and wood rosin ester:

• Gum rosin ester is approved for use as a direct food additive as a plasticizing agent in chewing gum (21 CFR 172.615).
• Gum rosin ester is approved for use as an indirect food additive in the manufacture of articles or components of articles intended for use in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or holding food (21 CFR 178.3870).
• Wood rosin ester is approved for use as a direct food additive (21 CFR 172.735) for use in citrus oils that are added to beverages to increase the density of the citrus oil and to act as an emulsifier at a maximum level of 100 parts per million (i.e., for the same conditions of use that T&R proposes for gum rosin ester). Wood rosin ester also is approved for use as a direct food additive as a plasticizing agent in chewing gum (21 CFR 172.615) and for use as an indirect food additive in the manufacture of articles or components of articles intended for use in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or holding food (21 CFR 178.3870).

T&R describes the manufacture of gum rosin ester from processed gum rosin. Gum rosin is obtained by extracting oleoresin gum from living pine trees (Pinus spp.) and refining it through washing, filtration and distillation. The refined gum rosin is esterified with glycerin under a nitrogen atmosphere. T&R provides specifications for gum rosin ester and notes that gum rosin ester is identified by comparing its infrared absorption against the standard provided in the Food Chemicals Codex, 4^th ed. (1996).

T&R describes generally available information about the composition of rosins, which are complex mixtures of soluble organic compounds that are derived from pine trees. Gum rosins are obtained by tapping a living pine tree to collect oleoresin (i.e., gum); wood rosins are collected by solvent extraction of aged and ground pine stump. Both gum rosins and wood rosins contain free organic acids (called resin acids) and a neutral fraction. Although the proportions of these two fractions can vary depending on both the source (i.e., the species and location of the pine tree) and the processing conditions, refined gum rosins and wood rosins generally contain approximately 90 percent resin acids and approximately 10 percent neutral fraction. The resin acids found in gum and wood rosins are C20 monocarboxylic diterpene acids that are grouped into four classes: abietane, pimarane, isopimarane, and labadane. Resin acids of the abietane, pimarane, and isopimarane classes differ only in the number and arrangement of double bonds or in the stereochemistry of the C-13 position. The neutral fraction of gum or wood rosin is composed of esters of resin acids, esters of fatty acids, and various unsaponifiable materials. The composition of the resin acid portion of the esters in the neutral fraction is similar to that of the acid fraction. The composition of the fatty acid portion of the esters in the neutral fraction is predominantly C18 or higher straight chain acids with varying degrees of unsaturation. Wood rosin contains small quantities of other organic materials that are present in the solvent extract of pine stumps and are incompletely removed by refining. Gum rosin contains other terpenes and hydrocarbons of generally high molecular weight and low volatility that are not stripped out in turpentine recovery.

T&R describes generally available information about the composition of gum rosin ester. The main component of gum rosin ester is glyceryl triabietate. However, other products may be formed, mainly as a result of incomplete esterification. T&R compares the composition of resin acids in gum rosins from various countries to that of typical wood rosin from the United States. T&R also compares typical physical and chemical properties of gum rosin to those of wood rosin. From these comparisons, T&R concludes that gum rosins are equivalent to wood rosins.

T&R describes its analysis of the physical properties, chemical properties, infrared spectra, and gas chromatography spectra of gum rosin ester and wood rosin ester. Based on this analysis, T&R concludes that gum rosin ester and wood rosin ester are comparable products.

T&R describes toxicological evaluations of gum rosin ester and wood rosin ester.

• T&R discusses memoranda, issued by FDA, associated with the agency's approval of wood rosin ester for use in citrus oils added to beverages and of gum rosin ester for use as a plasticizing agent in chewing gum. In these memoranda, FDA established a no-observed-adverse-effect level (NOAEL) for wood rosin ester based on toxicological studies conducted with wood rosin ester. FDA also concluded that, toxicologically, rosin esters from wood or gum sources are practically similar.
• T&R describes two unpublished 90-day studies conducted with gum rosin ester in rats. T&R obtained reports of these studies from a "White Paper" issued by the National Association of Chewing Gum Manufacturers and European Association of the Chewing Gum Industry (NACGM/EACGI). T&R notes that the primary study reports of these two 90-day studies were considered to be confidential business information and, thus, unavailable for review.
• T&R reports that the Joint Food and Agriculture Organization/World Health Organization's (FAO/WHO) Expert Committee on Food Additives (JECFA) reviewed the results of several unpublished pharmacokinetic studies and toxicity studies conducted with wood rosin ester. JECFA established an acceptable daily intake of 0 to 25 mg/kilogram body weight/day for the use of wood rosin ester as an emulsifier in beverages and in chewing gum based on a NOAEL established in a 13-week oral toxicity study in rats.

FDA's evaluation of the data and information in T&R's notice

Under sections 201(s) and 409 of the Federal Food, Drug, and Cosmetic Act (the FFDCA), a substance that is added to food is a food additive that requires premarket review and approval by FDA, unless the substance is generally recognized, among qualified experts, as having been generally shown to be safe under the conditions of its intended use. In the GRAS proposal, FDA proposed to establish a formal (albeit voluntary) procedure whereby a person who concludes that a use of a substance is not subject to the statutory provisions for premarket approval (because that use is GRAS) may communicate that view to FDA, the federal agency responsible for implementing those statutory provisions. The formal submission to FDA, which is known as a "GRAS notice," should be sufficient to convince qualified experts that FDA need not review the primary data that demonstrate safety.

As discussed in the GRAS proposal, a GRAS substance is distinguished from a food additive on the basis of the common knowledge about the safety of the substance for its intended use. There are two aspects to this common knowledge. First, the data and information relied on to establish safety must be generally available. Second, there must be a basis to conclude that there is consensus among qualified experts about the safety of the substance for its intended use. Neither aspect is, by itself, sufficient to satisfy the common knowledge element of the GRAS standard.

In evaluating whether the intended use of gum rosin ester is GRAS, T&R presents its view that gum rosin ester is toxicologically and chemically equivalent to wood rosin ester, that wood rosin ester is safe for use in citrus oils that are added to beverages, and that gum rosin ester therefore is also safe for use in citrus oils that are added to beverages. The basis for T&R's view includes the following:

• The view of its GRAS panel that no evidence exists in the available information on gum rosin ester that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when gum rosin ester is used at levels that are now current or that might reasonably be expected from its proposed use
• Memoranda, issued by FDA, associated with the agency's approval of wood rosin ester and gum rosin ester as food additives
• A generally available JECFA report that describes a series of unpublished studies conducted with wood rosin ester
• A generally available paper, prepared by a trade association, that reports results from studies that were conducted with gum rosin ester and that are considered to be confidential business information
• Generally available information about the composition of gum rosin and wood rosin
• Analytical data regarding the physical, chemical, and spectral properties of gum rosin ester and wood rosin ester.

During its evaluation of GRN 000108, FDA requested a copy of three generally available reports prepared by JECFA (Refs. 1-3). In two of these reports (Refs. 1 and 2), JECFA clearly states its view that gum rosin differs from wood rosin and that the toxicology of gum rosin ester is different from that of wood rosin ester. In the third report (Ref. 3), JECFA makes no comparisons between gum rosin ester and wood rosin ester.

Because the underlying data evaluated by T&R's GRAS panel are not generally available, T&R fails to satisfy the common knowledge element of the GRAS standard. In addition, because JECFA's publicly stated view about the differences between gum rosin and wood rosin contradicts T&R's view that gum rosin ester is chemically and toxicologically similar to wood rosin ester, there is no basis to conclude that there is consensus within the scientific community on a point that is central to T&R's evaluation of the safety of gum rosin ester.

Conclusions

FDA has evaluated the data and information in GRN 000108 as well as other available information. The notice does not provide a sufficient basis for a determination that glycerol ester of gum rosin is GRAS under the conditions of its intended use.

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).

References

1. Joint FAO/WHO Expert Committee on Food Additives (JECFA), forty-sixth meeting. 1996. Toxicological Evaluation of Certain Food Additives. WHO Food Additive Series 37. Geneva: World Health Organization.

2. Joint FAO/WHO Expert Committee on Food Additives (JECFA). 1997. Evaluation of Certain Food Additives and Contaminants. WHO Technical Report Series 868. Forty-sixth report of the Joint FAO/WHO Expert Committee on Food Additives. Geneva: World Health Organization.

3. Joint FAO/WHO Expert Committee on Food Additives (JECFA), forty-fourth meeting. Toxicological Evaluation of Certain Food Additives and Contaminants in Food. WHO Food Additive Series 35. Geneva: World Health Organization.