SYNTHETIC ANTIOXIDANTS IN FOODS

VII. SYNTHETIC ANTIOXIDANTS IN FOODS

Many antioxidants have been evaluated for use in foods as preservatives. Whereas natural antioxidants, (e.g., vitamin E) do not withstand processes such as frying and baking, syn- thetic antioxidants can survive these processes. Four synthetic antioxidants are particularly widespread in their use in foods: BHA, BHT, propyl gallate, and 2-(1,1-dimethylethyl)- 1,4-benzenediol, also known as tertiarybutyl hydroquinone (TBHQ). Although a number of synthetic substances have been studied as food antioxidants, relatively few are approved and listed in the Code of Federal Regulations (Code of Federal Regulations, 1998a) by the Food and Drug Administration for use in the United States. The limits on types of antioxidants and allowable concentrations vary from country to country, which can be a problem in international marketing. Among the food preservatives that are allowed to be directly added to foods are the following antioxidants: Anoxomer, BHA, BHT, ethoxy- quin, 4-hydroxymethyl-2,6-di-tert-butylphenol, TBHQ, and 2,4,5-trihydroxybutyrophe- none (THBP) (Code of Federal Regulations, 1998b). The phenolic antioxidants are quite effective and are often used at concentrations of less than 0.01% (Rajalakshmi and Nara- simhan, 1996). Other compounds that function as antioxidants are approved for direct addition to food and are on the list of food additives affirmed as generally recognized as safe (GRAS). Among the most prevalent of these substances are propyl gallate, lecithin, gum or resin guaiac, and glycine. Substances classified as antioxidants, when migrat- ing from food-packaging material (limit of addition to food, 0.005%), include BHA, BHT, dilauryl thiodipropionate, distearyl thiodipropionate, gum guaiac, nordihydroguaire- tic acid, propyl gallate, thiodipropionic acid, and 2,4,5-trihydroxy butyrophenone (Code of Federal Regulations, 1998b).

A. Synthetic Antioxidants Added Directly to Food

Commercial antioxidants are prepared as solids or blends of liquid. The blends of antioxi- dants are solubilized and thus are more readily added to foods during processing. Antioxi- dant mixtures are prepared in solvents such as propylene glycol, which is odorless, taste- less, and inert. BHT, however, is insoluble in propylene glycol, and carriers such as fat or the fat derivatives mono- and diglycerides can be used. Solvents such as alcohol or acetic acid are often used as antioxidant carriers they are usually removed later by a combination of heat and vacuum (Chipault, 1962). The commercial antioxidants usually are mixtures of phenolic antioxidants and synergists.

1. Anoxomer Anoxomer is a polymeric antioxidant that is prepared by condensation polymerization of

divinylbenzene (m- and p-) with tert-butylhydroquinone, tert-butyl-phenol, hydroxyani- divinylbenzene (m- and p-) with tert-butylhydroquinone, tert-butyl-phenol, hydroxyani-

10 ppm lead, 3 ppm arsenic or 1 ppm mercury. Anoxomer may be safely used as an antioxidant in food at a level of not more than 5000 ppm based on fat and oil content of the food.

2. Butylated Hydroxyanisole Butylated hydroxy hydroxyanisole (MW, 180.24 melting point, 48–55 °C; boiling point

264–270 °C) is a mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methox- oyphenol, with the 3-isomer being 90% or more of the mixture (Fig. 3). The molecule is

a ‘‘hindered’’ phenol, and the tert-butyl group ortho or meta to the hydroxyl group serves to suppress antioxidant activity. The steric hindrance is probably responsible for the rela- tive ineffectiveness of BHA in vegetable oils because the tertiary butyl group interferes with the antioxidant activity of the phenolic structure. The steric hindrance may account for the carry-through effect of BHA in fats used in baked foods. BHA is commonly used in combination with other primary antioxidants, such as gallates, to take advantage of synergistic effects. BHA has a strong phenolic odor that becomes particularly noticeable when an oil treated with this antioxidant is subjected to high temperatures such as in baking or frying operations. This water-insoluble, white, waxy solid is soluble in fats and oils. BHA is often produced in tablet form to prevent caking. BHA effectively controls the oxidation of animal fats, but is a relatively ineffective antioxidant in most vegetable oils. It is a particularly effective antioxidant for use in palm kernel and coconut oils, which are typically used in cereal and confectionery products. BHA provides good carry-through, which is the ability to be added to food, survive processing, and remain stable in food, especially in baked products. It is the most effective of all food-approved antioxidants for protecting the flavor and color of essential oils. BHA is also added to packaging materials, either being added directly to the wax used in making waxed inner liners or applied to the packaging as an emulsion.

BHA exhibits antioxidant properties and synergism with acids, BHT, propyl gallate, hydroquinone, methionine, lecithin, thiodipropionic acid, etc. This antioxidant is used es- pecially in foods, and the American Meat Institute Foundation proposed an antioxidant mixture known as AMIF-72 that contains 20% BHA, 6% propyl gallate, and 4% citric acid in propylene glycol (Budavari, 1989).

The food additive BHA, alone or in combination with other antioxidants permitted in food for human consumption, may be safely used in or on specified foods as follows (Code of Food Regulations, 1998d):

1. Total BHA must assay at 98.5% minimum, with a minimum melting point of

48 °C.

2. BHA may be used alone or in combination with BHT, as an antioxidant in foods, as follows: food (total BHT and BHA, ppm): dehydrated potato shreds (50); active dry yeast (1000 BHA only); beverages and desserts prepared from dry mixes (2 BHA only); dry breakfast cereals (50); dry diced glazed fruit (32 BHA only); dry mixes for beverages and desserts (90 BHA only); emulsion stabilizers for shortenings (200); potato flakes (50); potato granules (10); and sweet potato flakes (50).

3. To assure safe use of the additive BHA: (1) The label of any market package of the additive shall bear, in addition to the other information required, the name of the additive. (2) When the additive is marketed in a suitable carrier, the label shall declare the percentage of the additive in the mixture. (3) The label or labeling of dry mixes for beverages and desserts shall bear adequate directions for use to provide that beverages and desserts prepared from the dry mixes contain no more than 2 ppm BHA.

3. Butylated Hydroxytoluene Butylated hydroxytoluene (2,6-di-tert-butyl-p-cresol; 2,6-bis(1,1-dimethylethyl)-4-meth-

ylphenol; MW, 220.34; melting point, 70 °C; boiling point, 265°C) is a water-insoluble, white, crystalline solid antioxidant that is more soluble in food oils and fats than is BHA (Fig. 4). BHT is soluble in toluene, methanol, ethanol, isopropanol, methyl ethyl ketone, acetone, Cellosolve, petroleum ether, benzene, and most other hydrocarbon solvents. BHT is an antioxidant for foods, animal feed, petrol products, synthetic rubbers, plastics, animal and vegetable oils, and soaps. While it is effective in animal fats, BHT is not as effective in vegetable oils. BHT is frequently used in combination with BHA in foods because the two antioxidants are synergistic in their actions. The oxidative reactions of nuts and nut products are very responsive to this combination of antioxidants.

BHT is noted for its high-temperature stability and its carry-through effect in fats or shortenings in baked food. However, BHT is less effective than BHA because of the greater steric hindrance presented by two tert-butyl groups surrounding the hydroxyl group BHT is noted for its high-temperature stability and its carry-through effect in fats or shortenings in baked food. However, BHT is less effective than BHA because of the greater steric hindrance presented by two tert-butyl groups surrounding the hydroxyl group

The food additive BHT, alone or in combination with other permitted antioxidants, may be safely used in or on specified foods as follows (Code of Federal Regulations, 1998e):

1. Total BHT must assay at 99% minimum.

2. BHT may be used alone or in combination with BHA, as an antioxidant in foods, as follows: food (total BHT and BHA, ppm)—dehydrated potato shreds (50); dry breakfast cereals (50); emulsion stabilizers for shortenings (200); po- tato flakes (50); potato granules (10); and sweet potato flakes (50).

3. To assure safe use of the additive BHT: (1) The label of any market package of the additive shall bear, in addition to the other information required, the name of the additive. (2) When the additive is marketed in a suitable carrier, the label shall declare the percentage of the additive in the mixture.

Reische et al. (1998) postulated that the synergistic mechanism of BHA and BHT involves interactions of BHA with peroxy radicals to produce a BHA phenoxy radical. The BHA phenoxy radical can then abstract a hydrogen from the hydroxyl group of BHT; BHT thus replenishes hydrogen to BHA, which regenerates its effectiveness. According to Belitz and Grosch (1987), the BHT radical then can react with a peroxy radical, thus acting as a chain terminator.

4. Ethoxyquin Ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline; MW, 217.30; boiling point,

123–125 °C) is a yellow liquid antioxidant used principally in animal feed and as an anti- degradation agent for rubber. When used in oil, ethoxyquin is primarily in the form of a radical. Dimerization of the radical will inactivate the antioxidant (Reische et al., 1998). The Code of Federal Regulations states that ethoxyquin may be safely used as an antioxi- dant for preservation of color in the production of chili powder, paprika, and ground chili at levels not to exceed 100 ppm (Code of Federal Regulations, 1998f). Although approved for limited use in human foods, ethoxyquin has long been used effectively as an antioxidant in feeds used for poultry and swine production, mainly for the protection of carotenoids. Commercial antioxidant mixtures for feeds contain both chelators and at least two effective antioxidants to prevent oxidative rancidity. Protection of feeds allows producers to achieve optimal growth rate, reproductive efficiency, and liveability in intensively produced poul- try. The recommendation of the American Soybean Association (URL http:/ /www. pacweb.net.sg/asa ) is that antioxidants be incorporated into a program comprising good manufacturing practices with appropriate quality control over ingredients, adequate rota- tion of inventory, and consumption of rations within one week of manufacture. The FDA has established tolerances for residues of ethoxyquin in or on edible products of animals as follows: 5 ppm in or on the uncooked fat of meat from animals except poultry, 3 ppm in or on the uncooked liver and fat of poultry, 0.5 ppm in or on the uncooked muscle

Extensive research has been done on the effects of feeding exotic birds ethoxyquin at 20% greater concentration than is used in normal feeds over a 5-year period and on feeding dogs over an 11-year period; dogs are the species most sensitive to potential effects of ethoxyquin. A Kaytee Avian Research Center (2000) report states that ‘‘To date, no ethoxyquin-related tissue changes have occurred, even in the 11 year feeding group. This is the only test ever conducted on ethoxyquin use in psittacine species and is now one of the longest and largest tests conducted in any specie. There is no legitimate reason to believe that any of the commercial antioxidants are a significant risk compared to the risk of unprotected food products.’’

5. 4-Hydroxymethyl-2,6-di-tert-butylphenol The food additive 4-hydroxymethyl-2,6-di-tert-butylphenol may be safely used in food

in accordance with the following proscribed conditions (Code of Federal Regulations, 1998g): (1) This food additive must have a solidification point of 140–141 °C. (2) As an antioxidant, it may be used alone or in combination with other permitted antioxidants. (3) The total amount of all antioxidants added to such food shall not exceed 0.02% of the oil or fat content of the food, including the essential oil content of the food.

6. 2-(1,1-Dimethylethyl)-1,4-Benzenediol 2-(1,1-Dimethylethyl)-1,4-benzenediol (TBHQ; MW, 166.22; boiling point, 300 °C; melt-

ing point, 126.5–128.5 °C), also known as tertiary butylhydroquinone (Fig. 5), is the most recently developed major phenolic antioxidant for food use. TBHQ is a white to light tan crystalline solid that effectively increases oxidative stability (shelf-life) of polyunsaturated food fats and oils. Features that make this antioxidant favorable are its moderate solubility (5–10%) in fats and oils, its slight (1%) water solubility and its lack of discoloration with metals, such as iron. TBHQ is the best antioxidant for protecting frying oils against oxida- tion, and it provides good carry-through to the finished product. However, TBHQ is rela- tively ineffective in baking applications. The response of vegetable oils to treatment with TBHQ is generally greater than with other approved primary antioxidants. This compound filled a need for an antioxidant for polyunsaturated oils, such as safflower seed oil. TBHQ also improves the color and stability of hydrogenated fats. TBHQ used in combination with citric acid further enhances its stabilizing properties, primarily in vegetable oils, shortenings, and animal fats. However, combination of TBHQ with propyl gallate is not permitted.

TBHQ can be safely used as an antioxidant in food in accordance with the following prescribed conditions (Code of Federal Regulations, 1998h): (1) The additive must have

a melting point of 126.5–128.5 °C. (2) TBHQ may be used as an antioxidant alone or in combination with BHA and/or BHT. (3) The total antioxidant content of a food containing the additive must not exceed 0.02% of the oil or fat content of the food, including the essential oil content of the food.

7. 2,4,5-Trihydroxybutyrophenone 2,4,5-Trihydroxybutyrophenone (THBP; MW, 196; melting point, 149–153 °C) is a tan

powder that is slightly soluble in water, moderately soluble in fats, soluble in alcohol, propylene glycol, and paraffin. This antioxidant can brown in the presence of metals. The food additive THBP may be safely used in food in accordance with the following condi- tions (Code of Federal Regulations, 1998i): (1) The additive must have a melting point of 149–153 °C. (2) THBP can be used as an antioxidant alone or in combination with other permitted antioxidants. (3) The total antioxidant content of a food containing TBHQ must not exceed 0.02% of the oil or fat content of the food, including the essential oil content of the food.

B. Antioxidants Generally Recognized as Safe

1. Propyl Gallate Propyl gallate (3,4,5-trihydroxybenzoic acid propyl ester; MW, 212.20; melting point,

150 °C; decomposes above 148°C) is a white to light gray, crystalline antioxidant that is partially soluble in water, alcohol, ether, vegetable oils, and lard (Fig. 6). Propyl gallate is used as an antioxidant in foods, fats, oils, ethers, emulsions, waxes, and transformer oils. This antioxidant is used to prevent rancidity in meat products such as rendered fats or pork sausage. The low oil solubility of propyl gallate makes this antioxidant difficult to incorporate into fats and oils, and its solubility in water makes it more likely to complex with iron and iron salts, which causes dark discoloration in some applications. Propyl gallate is usually used with citric acid to eliminate this unappealing discoloration. The low melting point of propyl gallate renders it ineffective at temperatures greater than 190 °C for frying. As a result of heat lability, propyl gallate provides little or no carry- through protection in many heat-processed foods. This is especially true when the foods are alkaline, such as in some baked goods. Propyl gallate is synergistic with BHA and

BHT, and the combined effects provide improved storage stability and carry-through pro- tection. Some countries allow the use of longer-chain esters, octyl and dodecyl gallates.

The Code of Federal Regulations (1998j) specifies propyl gallate use as follows: (1) Propyl gallate is the n-propylester of 3,4,5-trihydroxybenzoic acid. The natural occur- rence of propyl gallate has not been reported. Propyl gallate is commercially prepared by esterification of gallic acid with propyl alcohol followed by distillation to remove excess alcohol. (2) The ingredient meets the specifications of the Food Chemicals Codex, 3d ed., 1981. (3) The ingredient is used as an antioxidant. (4) The ingredient is used in food at levels not to exceed good manufacturing practice, which results in a maximum total con- tent of antioxidants of 0.02% of the fat or oil content, including the essential (volatile) oil content, of the food.

2. Gum Guaiac Gum guaiac, also known as resin guaiac (melting point, 85–90 °C) is insoluble in water

but freely soluble in alcohol, chloroform, ether, alkalis. The antioxidant properties of gum guaiac were first described by Grettie (1933) in the early 1930s and was the first antioxi- dant to be approved for use in lard (Chipault, 1962). Gum guaiac is more effective as a stabilizer of animal fats than of vegetable oils. Gum guaiac is a relatively weak antioxidant, and it has not been used to any large extent in recent years. This substance is generally recognized as safe when used in edible fats or oils in accordance with good manufacturing or feeding practice and can be used at 0.1% (equivalent antioxidant activity, 0.01%).

3. Nordihydroguaiaretic Acid Nordihydroguaiaretic acid (NDGA) is the chemical 4,4 ′-(2,3-dimethyl-1,4-butanediyl)

bis[1,2-benzenediol]. NDGA was first isolated from the creosote bush, and it occurs with gums, resins, and waxes on the surface of leaves. This white, crystalline solid has a melting point of 184–185 °C and is slightly soluble in water and dilute acid. Lundberg et al. (1944) first described its antioxidant properties, and it has been used as an antioxidant in foods, especially animal fats (Chipault, 1962). Now, however, food containing NDGA is deemed to be adulterated and in violation of the act based upon an order published in the Federal Register of April 11, 1968 (33 FR 5619).

C. Synergistic Antioxidants

Several considerations are basic to the use of phenolic antioxidant formulations in food fats and oil (Sherwin, 1989). Antioxidants are combined to take advantage of their different types of effectiveness. Specific combinations avoid or minimize solubility or color prob- lems presented by the individual antioxidants; combinations permit better control and accuracy of application; combinations enable more complete distribution or solution of antioxidants and chelating agents in fats and oils; some combinations of antioxidants are more convenient to handle than individual antioxidant compounds; and some provide syn- ergistic effects offered by some antioxidant combinations.

Over three decades ago, Chipault (1962) reviewed the then current information about antioxidant synergists. It was clear that at the time some compounds, which by themselves have very little effect on the oxidation of fats, may enhance or greatly prolong the antioxy- genic action of primary antioxidants. The mechanisms of synergism vary, and while part of the activity of synergists is due to their inactivation of prooxidant metals, they may

Many low molecular weight hydroxy acids or amino acids exhibit synergistic activ- ity. Among synergistic antioxidants are substituted mercaptopropionic acids, such as 3,3- thiodipropionic acid, phospholipids, citric acid, ascorbic acid, and phosphoric acids. As stated, mixtures of primary antioxidants, such as propyl gallate and BHA and mixtures of BHA and BHT, are used synergistically in some food systems.

1. 3,3-Thiodipropionic Acid 3,3-Thiodipropionic acid (3,3 ′-thiobis[propanonic acid]; MW, 178.20; melting point,

134 °C) is an antioxidant that is freely soluble in hot water, alcohol, and acetone. In addition to being used as a food antioxidant, it is added to plasticizers, lubricants, soap products, and polymers of ether. Thiodipropionic acid is a slightly effective antioxidant when used alone in lard, but it is a powerful synergist when used in combination with BHA (Kraybill et al., 1949).

2. Lecithin Phospholipids can function as either antioxidants or prooxidants. Most of the antioxidant

effect noted appears to result from the chelation of metal ions. Commercial lecithin is a naturally occurring mixture of the phosphatides of choline, ethanolamine, and inositol, with smaller amounts of other lipids. It is isolated as a gum following hydration of solvent- extracted soy, safflower, or corn oils. Lecithin can be bleached by hydrogen peroxide and benzoyl peroxide and dried by heating. Lecithin can be used in food with no limitation other than current good manufacturing practice.

3. Citric Acid Citric acid, 2-hydroxy-1,2,3-propane-tricarboxylic acid (MW, 192.12), is highly soluble

in water and primarily insoluble in fats. Citric acid is a natural antioxidant that is active in vegetable oils but without effect in lard, lard esters, or the purified, distilled esters of cottonseed oil. Although citric acid can counteract the prooxidant effect of iron, it can act as a synergist in the presence of a phenolic synthetic antioxidant when no metallic accelerators are present. At least two free carboxylic groups are necessary for antioxidative potency (Chipault, 1962). Although decomposed by heat, the thermal decomposition prod- ucts are also good synergists. Citric acid is listed among the specific substances affirmed as GRAS.

4. Ascorbic Acid Ascorbic acid (3-oxo-L-gulofuranolactone; MW, 176.12) is a crystalline substance that

decomposes near 160 °C. This natural antioxidant, which is extremely insoluble in fats, was first used as an antioxidant to improve the stability of mayonnaise. The synergistic antioxidant effect of ascorbic acid can be ascribed partly to the binding of metal ions. The free acid acts as a synergist with most phenolic antioxidants, but not with gallic acid (Filer et al., 1944). Ascorbic acid is among the substances affirmed as GRAS.