GRAS status

Maltitol, lactitol, isomalt, maltitol solutions (symps), and hydrogenated starch hydrolysates (HSH) have GRAS petitions filed with the FDA and are being sold commercially under self-determined GRAS status. Maltitol, owing to its lower negative heat of solution, is often preferred over mannitol as the... 

In 1974, a petition for affiimation of the GRAS status of miracle fmit was submitted by the Miralin Company, mainly based on the fact that miracle fmits have been consumed by humans since before 1958. In 1977, the petition was denied by the FDA. However, miraculin remains a research curiosity. Its stmcture was elucidated in 1989 (125). Another protein, curculin [151404-13-6] (126), has also been reported to exert a sweet-inducing activity similar to miraculin. 

Stannous chloride, an FDA-approved direct food additive with GRAS status, has also been extensively studied (59—62). In three FDA-sponsored studies, it was determined that stannous chloride is nonmutagenic in rats when administered orally up to 50 mg/kg to pregnant mice for ten consecutive days, stannous chloride has no discernible effect on nidation or on maternal or fetal survival and, when administered orally at 41.5 mg/kg to pregnant rabbits for 13 consecutive days, it produced no discernible effect on nidation or on maternal or fetal survival (63—65). 

Treatment of ceUulose with acids results in preferential hydrolysis in the more accessible amorphous regions and produces a product known as microcrystalline ceUulose (MCC). MCC is used to prepare fat-free or reduced-fat food products, to strengthen and stabilize food foams, as a tableting aid, and as a noncalotic bulking agent for dietetic foods. It has GRAS status. 

A commercial bacterial cellulose product (CeUulon) was recently introduced by Weyerhaeuser (12). The fiber is produced by an aerobic fermentation of glucose from com symp in an agitated fermentor (13,14). Because of a small particle diameter (10 P-m), it has a surface area 300 times greater than normal wood cellulose, and gives a smooth mouthfeel to formulations in which it is included. CeUulon has an unusual level of water binding and works with other viscosity builders to improve their effectiveness. It is anticipated that it wiU achieve GRAS status, and is neutral in sensory quaUty microcrystaUine ceUulose has similar attributes. 

Health and Safety. FEMA has examined cinnamaldehyde and estabhshed its GRAS status (No. 2286). The material has been used in some fragrance compositions, but RJEM (34) has noted its potential for sensiti2ation and limited the use in perfumes for skin contact at 1% in the formula. Eugenol and limonene have been used in conjunction with cinnamaldehyde as quenchers to neutrali2e the irritation reaction that some individuals have toward this aldehyde. 

Health and Safety. Cinnamyl alcohol has been evaluated by FEMA and given GRAS status (FEMA No. 2294). Two of its esters, cinnamyl cinnamate (FEMA No. 2298) and cinnamyl acetate (FEMA No. 2293), ate also used extensively in flavor and fragrance compositions. Cinnamyl alcohol has also been tested by RIFM (48) and found to be safe for use. There have been reported cases of irritation and several manufacturers market a desensitized alcohol for use in fragrance appHcations. 

Other ingredients were granted GRAS status individually. All of these GRAS ingredients are included in the regulations found in 21 CFR Part 182. 

Conditions of intended use. The GRAS status is determined, in part, based on the intended conditions of use of the flavoring substance through the calculation of a possible average daily intake (PADI) and a per capita exposure estimate. 

Anon. GRAS status of foods and food additives. EedRegist 1976 41 38,644. Katsuzaki, H., S. Kawakishi, and T. Osawa. Structure of novel antioxidant lignan triglucoside isolated from sesame seed. Heterocycles 1993 36(5) 933-936. 

Antioxidant-Treated Beef Patties. The effect of several primary antioxidants, PG, TBHQ, Tenox 20 (which contains TBHQ and citric acid) and Tenox 4A (which contains BHA and BHT) were also evaluated by instrumental, chemical and sensory methods for their effectiveness in raw/stored and cooked/stored beef, see Tables 1-4. These particular antioxidants were chosen based on their antioxidant effects on MFD as determined previously (14) and because of their GRAS status. Experimental samples were prepared similarly to those of the 0-and 2-day controls, except the antioxidants, either dissolved or suspended in water, were mixed into the raw ground meat. 

Vanilla flavour is not only determined and characterised by the vanillin molecule, but also by many more phenolic compounds and vanillin derivatives. Two examples of molecules that recently obtained FEMA-GRAS status are vanillyl ethyl ether and vanillin 2,3-butanediol acetal (Scheme 13.11). Vanillin can be hydrogenated to form vanillyl alcohol, which is also used in vanilla flavours. Vanillyl alcohol can be reacted with ethanol to form vanillyl ethyl ether. Vanillin can also form an acetal with 2,3-butanediol (obtained by fermentation of sugars) catalysed byp-toluene sulfonic acid in toluene. 

Some safety issues for excipients with a history of use may be addressed by citations of the clinical and nonclinical database, marketing history, or regulatory status of the compound, e.g., GRAS status as a direct food additive may support oral administration of that product up to the levels allowed in foods. 

The U.S. FDA states in the Guidance for Nonclinical Studies for Development of Pharmaceutical Excipients (2) that they will continue to consider factors such as use in previously approved products, GRAS-status, or a food additive to evaluate the safety of a new excipient. The FDA states . .. an excipient with documented prior human exposure under circumstances relevant to the proposed use may not require evaluation in a full battery of toxicology studies... FDA also states under some circumstances (e.g., similar route of administration, level of exposure, patient population, and duration of exposure) other factors can adequately qualify an excipient (2). The sponsor of a new excipient should meet with the FDA to provide information regarding the toxicology, chemistry, manufacturing, and controls necessary to evaluate a potential new excipient. 

In the past, petitioners filed petitions with FDA to review the GRAS status of a substance and affirm the substance as GRAS. In 1997, FDA proposed to replace this GRAS affirmation petition process with a proposed voluntary notification procedure where any interested party may notify FDA of the determination that a substance is... 

In a recent article, the FDA stated For excipients with a history of use, it may be possible to adequately address some or all of the safety issues through citation of the existing nonclinical and clinical database, marketing history, or regulatory status of the compound (e.g., GRAS status as a direct food additive may adequately support oral administration of that compound up to the levels permitted in foods) (25). Therefore, it appears reasonable that the FDA would consider the use safety data based on the food additive regulatory status of an excipient to evaluate the safety of the excipient. If a new excipient has undergone a food additive safety review, this may reduce the perceived risks associated with the development and use of a new excipient. 

Health and Safety. This material has a Generally Recognized As Safe (GRAS) status indicated by the Flavor and Extract Manufacturers Association for use in flavors and by the Council of Europe for use as a flavor. Benzyl alcohol satisfies the most current guidelines published by (lie International Fragrance Association (IFRA) which governs the use of fragrance materials. 

Federal Register. Sulfiting agents revocation of GRAS status for use on fruits and vegetables intended to be served or sold raw to consumers. 51(131) 25021—25026, 1988. 

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