In Safety Testing We Trust: Strengthening Natural Evaluation

William Troy

*Editor’s Note: This paper has been republished from the IFEAT World newsletter

For 56 years the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) has served as the primary, independent body evaluating the safety of flavor ingredients. This Expert Panel evaluates flavor ingredients to determine if they can be considered “Generally Recognized As Safe” (GRAS) for their intended use as flavor ingredients, consistent with the 1958 Food Additives Amendment to the Federal Food, Drug and Cosmetic Act. Currently, the FEMA Expert Panel has determined more than 2,800 flavor ingredients have met the criteria for GRAS status under conditions of intended use as flavor ingredients.

Since its inception, the FEMA GRAS program has continued apace with new materials being reviewed and added to the list, as well as updated reevaluations of materials that already had GRAS status. In addition to conducting reviews for chemically defined individual ingredients, the Expert Panel has also regularly evaluated and updated the scientific approaches used in its review processes.

In 2004 the Expert Panel published its updated process specifically for the safety evaluation of Natural Flavor Complexes (NFCs). NFCs are mixtures of naturally-occurring chemicals, which have been obtained by subjecting botanical materials to various physical separation techniques, such as extraction or distillation. The resulting products, for example essential oils, represent the aroma components of these natural products. The FEMA Expert Panel’s approach to evaluating the safety of a natural flavor complex is similar to that outlined by the Joint WHO/FAO Expert Committee on Food Additives (JECFA) as published in their technical report series following the 2003 and 2004 meetings. It begins with an understanding of the chemical composition of each commercial product, followed by a review of the history of dietary use. The NFCs are then grouped into classes having structural similarity and a toxicological review proceeds. If the available data supports the safety in use of the NFC its GRAS status is confirmed.

Defining NFCs

In 2014 flavor industry discussions began to focus on the need for a systematic GRAS re-review program that would concentrate solely on NFCs. A key driver in this discussion was the International Federation of Essential Oils and Aroma Trades (IFEAT), whose major focus is on NFCs. IFEAT was joined by FEMA and the International Organization of the Flavor Industry (IOFI) and within the next year, an agreement was reached for a robust scientific review program for these materials. By this agreement, project support is provided by IFEAT and IOFI; IOFI scientific staff takes the lead in driving the program, working collaboratively with IFEAT scientific support and with FEMA scientific staff who assemble the available data for the actual GRAS reviews by the Expert Panel.

This program makes specific use of the so-called “Naturals Paradigm”a represented in the Panel’s 2004 publication [1]. The basic premise of the FEMA Expert Panel’s Naturals Paradigm is the evaluation of an essential oil based on its chemical composition. By organizing the chemical constituents into congeneric groups of similar chemical and toxicological properties, the risk posed by each congeneric group can be considered separately.

Essential oils are chemical mixtures and, for most essential oils, the analytical technology exists so their composition can be accurately determined and evaluated for safety. This approach is scientifically based, transparent and comprehensive to assure the commercially relevant NFCs destined for consumer exposure are the materials evaluated. It also allows for evaluation of mixtures, such as those derived from botanicals, which may display variability due to source country and harvesting time and conditions. During the course of its evaluation the Panel also reviews and considers the results of toxicological testing conducted on the NFC itself, which can also be useful despite this potential variability. The current FEMA GRAS list contains about 350 NFCs, and it has been determined that 250 of these would be appropriate for GRAS re-affirmation. The 100 or so materials that would not be included in this review are categorized as whole spices, leaves and gums—which are already GRAS—as well as newer NFCs that were reviewed when the naturals paradigm was developed in 2004.

Using the results of global poundage surveys conducted regularly by FEMA to track flavor material use, the NFCs are prioritized for reevaluation with the highest use materials being in the highest priority grouping. Materials having known biological activity also receive high priority attention. A request for compositional data is sent to the entire industry for each group of materials; the scope of this request maximizes the opportunity for assembling a robust data package. Then the so-called congeneric groupings of the NFCs are created based on materials having individual components of similar structural classes. FEMA scientific staff next assembles all available safety data for these groups and, together with composition data, all information is provided to the Expert Panel for its review.

If the Panel determines that additional information is needed to complete its review, FEMA scientific staff organizes the necessary testing or information gathering. Finally, the results of the Panel review are published in an appropriate peer-reviewed journal.

Breakdown of Review Program

The re-affirmation program is planned to complete the review of about 50 materials per year, with a five-year timeline for overall project completion. A total of 149 materials are scheduled to have Panel review completed by the first quarter of 2018 with two more groups following that in subsequent years. The first group of materials (49 total) to be reviewed was the citrus products, broken down as follows: lemon (six); orange, high volume (13); orange, moderate volume (14); lime (six); grapefruit (five); and petitgrain (five). As of this writing, the Panel review of these was completed and a document for publication is in final stages of preparation.

The second group review is in progress, with the call for data being completed and the data being prepared for review by the Panel. There are five groups of materials (total 44) being addressed: mint (13); cinnamon (eight); alkoxybenzene-containing oils (including basil oil, nutmeg oil, allspice oil, etc.) (14); eugenol (seven); and two unique materials, walnut hull extract and haw bark extract. A draft document for publication is expected in mid-2017.

Finally, a third call for data has just been issued for a disparate group of some 56 NFCs materials, all of them FEMA GRAS. The same pattern of data collection, review and publication will be followed with the latter scheduled for mid-2018.

Assuring Safety

The outcome of this program will clearly strengthen the safety support for both the natural products themselves and for those consumer products in which they are contained. It may also allow for critical decisions to be made about future usage patterns for some NFCs. If, for example, there are some low usage materials with gaps in the supporting data, industry members will have to decide whether to invest in generating the additional data. Likewise, it may be possible that, for some high usage materials, additional data points are recommended to supplement the data support dossiers that already exist.

With the conclusion of this program, those naturally occurring flavoring materials that have been in such long use will have all undergone the same rigorous safety review. The review is in accordanance with updated processes for scrutiny, as the synthetic flavor materials that must have each qualified for inclusion in the FEMA GRAS list. This is a major step for the flavor industry, and a testimony to its commitment to the assurance of safety of its materials.

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