sign in sign up
<<
Home , Rennet

32904 Federal Register / Vol. 60, No. 122 / Monday, June 26, 1995 / Rules and Regulations

(a) The additive is prepared by 21 CFR PART 184 I. Introduction reacting oil in toluene with [Docket No. 84G±0257] In accordance with the procedures hydrogen peroxide and formic acid. described in § 170.35 (21 CFR 170.35), (b) It meets the following Preparations From Animal and the Ad Hoc Enzyme Technical specifications: Plant Sources; Affirmation of Gras Committee (now the Enzyme Technical Status as Direct Food Ingredients Association), c/o Miles Laboratories, (1) Epoxidized soybean oil contains Inc., 1127 Myrtle St., Elkhart, IN 46514, AGENCY: Food and Drug Administration, oxirane oxygen, between 7.0 and 8.0 submitted a petition (GRASP 3G0016) HHS. percent, as determined by the American requesting that the following enzyme Oil Chemists’ Society (A.O.C.S.) method ACTION: Final rule. preparations be affirmed as GRAS for Cd 9–57, ‘‘Oxirane Oxygen,’’ reapproved SUMMARY: The Food and Drug use in food: 1989, which is incorporated by Administration (FDA) is affirming that (1) Animal-derived enzyme reference in accordance with 5 U.S.C certain enzyme preparations derived preparations: Catalase (bovine liver); 552(a) and 1 CFR part 51. Copies are from animal and plant sources are , animal; ; rennet; rennet, available from the American Oil generally recognized as safe (GRAS) for bovine; and trypsin. (2) Plant-derived enzyme Chemists’ Society, P. O. Box 3489, use as direct food ingredients. This preparations: Bromelain; malt; and Champaign, IL 61826–3489, or may be action is a partial response to a petition papain. examined at the Division of Petition filed by the Ad Hoc Enzyme Technical (3) Microbially-derived enzyme Control (HFS–215), Center for Food Committee (now the Enzyme Technical preparations: , var. Safety and Applied Nutrition, Food and Association). The following enzyme (lipase, catalase, glucose oxidase, and Drug Administration, 1110 Vermont preparations derived from animal carbohydrase); Bacillus subtilis, var. Ave. NW., suite 1200, Washington, DC, sources are affirmed as GRAS in this (carbohydrase and mixtures); final rule: Catalase (bovine liver), or at the Office of the Federal Register, Rhizopus oryzae (carbohydrase); and animal lipase, pepsin, trypsin, and 800 North Capitol St. NW., suite 700, Saccharomyces species (carbohydrase). Washington, DC. pancreatin (as a source of protease FDA published a notice of filing of activity). The following enzyme this petition in the Federal Register of (2) The maximum iodine value is 3.0, preparations derived from plant sources as determined by A.O.C.S. method Cd April 12, 1973 (38 FR 9256), and gave are affirmed as GRAS in this final rule: interested persons an opportunity to 1–25, ‘‘Iodine Value of Fats and Oils Bromelain, ficin, and malt. Wijs Method,’’ revised 1993, which is submit comments to the Dockets DATES: Effective June 26, 1995. The incorporated by reference in accordance Management Branch (HFA–305), Food Director of the Office of the Federal and Drug Administration, rm. 1–23, with 5 U.S.C. 552(a) and 1 CFR part 51. Register approves the incorporation by The availability of this incorporation by 12420 Parklawn Dr., Rockville, MD reference in accordance with 5 U.S.C. 20857. The petition was amended by reference is given in paragraph (b)(1) of 552(a) and 1 CFR part 51 of a certain notices published in the Federal this section. publication listed in 21 CFR Register of June 12, 1973 (38 FR 15471), (3) The heavy metals (as Pb) content 184.1024(b), 184.1034(b), 184.1316(b), proposing affirmation that microbially can not be more than 10 parts per 184.1415(b), 184.1443a(b), 184.1583(b), derived enzyme preparations million, as determined by the ‘‘Heavy 184.1595(b), and 184.1914(b), effective (carbohydrase, lipase, and protease) Metals Test,’’ Food Chemicals Codex, 3d June 26, 1995. from A. oryzae are GRAS for use in ed. (1981), p. 512, Method II (with a 2- FOR FURTHER INFORMATION CONTACT: food; in the Federal Register of August gram sample and 20 microgram of lead Laura M. Tarantino, Center for Food 29, 1984 (49 FR 34305), proposing ion in the control), which is Safety and Applied Nutrition (HFS– affirmation that the enzyme incorporated by reference. Copies are 206), Food and Drug Administration, preparations ficin, obtained from 200 C St. SW., Washington, DC 20204, available from the National Academy species of the genus (fig tree), and 202–418–3090. Press, 2101 Constitution Ave. NW., Box pancreatin, obtained from bovine and porcine pancreas, are GRAS for use in 285, Washington, DC 20055, or may be SUPPLEMENTARY INFORMATION: food; and in the Federal Register of June examined at the Division of Petition Table of Contents 23, 1987 (52 FR 23607), proposing Control (HFS–215), Center for Food I. Introduction affirmation that the enzyme preparation Safety and Applied Nutrition, Food and II. Standards for GRAS Affirmation protease from A. niger is GRAS for use Drug Administration, 1110 Vermont III. Background in food. In the June 23, 1987, notice, Ave. NW., suite 1200, Washington, DC, A. FDA also noted the petitioner’s or at the Office of the Federal Register, B. Enzyme Nomenclature assertion that pectinase enzyme C. Enzyme Preparations that are the 800 North Capitol St. NW., suite 700, preparation from A. niger and lactase Washington, DC. Subject of this Document 1. Introduction enzyme preparation from A. niger are (c) The additive is used as a halogen 2. Animal-derived Enzyme Preparations included under carbohydrase enzyme stabilizer in brominated soybean oil at 3. Plant-derived Enzyme Preparations preparation from A. niger, and that a level not to exceed 1 percent. IV. Safety Evaluation invertase enzyme preparation from A. Pre-1958 History of Use in Food Saccharomyces cerevisiae and lactase Dated: June 14, 1995. B. Corroborating Evidence of Safety enzyme preparation from 1. The Enzyme Component Fred R. Shank, Kluyveromyces marxianus are both 2. Enzyme Sources and Processing Aids included under carbohydrase enzyme 3. Dietary Exposure Director, Center for Food Safety and Applied preparation from species of the genus Nutrition. V. Comments VI. Conclusions Saccharomyces. The agency further [FR Doc. 95–15349 Filed 6–23–95; 8:45 am] VII. Environmental Impact noted that, therefore, pectinase enzyme BILLING CODE 4160±01±F VIII. Economic Impact preparation from A. niger, lactase IX. References enzyme preparation from A. niger, Federal Register / Vol. 60, No. 122 / Monday, June 26, 1995 / Rules and Regulations 32905 invertase enzyme preparation from S. preparation derived from malted barley important functional properties of cerevisiae, and lactase enzyme extracts. Likewise, FDA’s determination enzymes (Ref. 6). The practical preparation from K. marxianus were to of the GRAS status of the enzyme applications of enzymes used in food be considered part of the petition. preparation pancreatin includes only processing include the conversion of Interested persons were given an the use of pancreatin as a protease. starch to sugars in brewing, the opportunity to submit comments to the II. Standards for GRAS Affirmation tenderizing of sausage casings and meat, Dockets Management Branch (address and the partial hydrolysis (breakdown) above) on each amendment. Pursuant to § 170.30 (21 CFR 170.30) of proteins that would otherwise form a After the petition was filed, the and 21 U.S.C. 321(s), general haze when beer is chilled (Ref. 7). agency published, as part of its recognition of safety may be based only comprehensive safety review of GRAS on the views of experts qualified by B. Enzyme Nomenclature substances, two GRAS affirmation scientific training and experience to Enzymes were originally known regulations that covered three of the evaluate the safety of substances principally by their trivial (common or enzyme preparations from animal and directly or indirectly added to food. The historical) names. These trivial names plant sources included in the petition. basis of such views may be either typically were based on one of two These two regulations are: (1) scientific procedures or, in the case of methods of nomenclature: (1) By the § 184.1685 Rennet (animal derived) (21 a substance used in food prior to addition of ‘‘-in’’ or ‘‘-ain’’ as a suffix to CFR 184.1685), which was published in January 1, 1958, experience based on a root indicating the source of the the Federal Register of November 7, common use in food. General enzyme (e.g., papain from papaya or 1983 (48 FR 51151) and includes the recognition of safety based upon pancreatin from pancreas); or (2) by the petitioned enzyme preparations rennet scientific procedures requires the same addition of the suffix ‘‘-ase’’ to a root and bovine rennet; and (2) § 184.1585 quantity and quality of scientific indicating the (specific Papain (21 CFR 184.1585), which was evidence as is required to obtain reactant) for the enzyme (e.g., lactase, published in the Federal Register of approval of a food additive and which acts on the substrate lactose) (Ref. October 21, 1983 (48 FR 48805). The ordinarily is based upon published 8). Some , however, have agency concludes that rennet, bovine studies, which may be corroborated by trivial names that are not based on rennet, and papain are already affirmed unpublished studies and other data and either of these two methods (e.g., as GRAS and listed in existing information (§ 170.30(b)). General trypsin). regulations and need not be addressed recognition of safety through experience In 1956, the Third International further. based on common use in food prior to Congress of the International Union of In letters to FDA (Refs. 1 and 2), the January 1, 1958, may be determined Biochemistry (IUB) organized a petitioner asserted that the enzyme without the quantity or quality of Commission on Enzymes to devise a preparation malt (amylase) includes scientific evidence required for approval systematic strategy for naming enzymes. extracts from germinated (malted) barley of a food additive regulation, and The system developed by the or ungerminated (unmalted) barley. In ordinarily is based upon generally Commission on Enzymes combined a addition, certain published references available data and information. naming system and a numbering system (Refs. 3 and 4) submitted by the For the enzyme preparations from (Ref. 8). With the exception of most petitioner describe the enzyme animal and plant sources that are the proteases, the systematic name is preparation pancreatin as a substance subject of this document, the Enzyme derived from the names of the substrate, containing the enzymes amylase, lipase, Technical Association based its request product, and type of reaction.2 The and protease. for affirmation of GRAS status on a systematic number is based on the class history of safe food use prior to 1958. In In a notice published in the Federal and subclasses to which the enzyme the preamble to a proposed rule Register of September 20, 1993 (58 FR belongs. The two classes of enzymes in amending § 170.30, which was 48889), the agency announced that the the numbering system relevant to this petitioner had requested that the published in the Federal Register of document are class 1, following enzyme preparations be July 2, 1985 (50 FR 27294) (final rule (e.g., catalase), which are active in withdrawn from the petition without published in the Federal Register of biological oxidation and reduction; and prejudice to the filing of a future May 10, 1988 (53 FR 16544)), FDA class 3, (e.g., glycosidases petition: (1) Pancreatin used for its stated that general recognition of safety (carbohydrases), , and proteases), lipase activity, (2) pancreatin used for through experience based on common which catalyze the splitting of chemical its amylase activity, and (3) amylase use in food requires a consensus on the bonds by the addition of water. derived from unmalted barley extract. In safety of the substance among the The following examples illustrate the that notice, the agency stated that, in community of experts who are qualified trivial name, functions, and Enzyme light of the petitioner’s request, any to evaluate the safety of food Commission (EC) name and number of future action by FDA on the petition ingredients. enzymes that are components of some of would not include a determination of III. Background the enzyme preparations that are the the GRAS status of these three enzyme subject of this document (Refs. 9 preparations. A. Enzymes This final rule is a partial response to through 11). Enzymes are proteins or conjugated α-amylase. Hydrolysis of α-1,4-glucan the petition and addresses only enzyme 1 proteins, produced by plants, animals, bonds in polysaccharides (starch, preparations from animal and plant and microorganisms, that function as glycogen, etc.), yielding dextrins and sources. Microbial enzyme preparations biochemical catalysts (Ref. 5). Further, oligo- and monosaccharides (1,4-α-D- will be dealt with separately in a future most enzymes are very specific in their glucan glucanohydrolase, EC 3.2.1.1). issue of the Federal Register. ability to catalyze only certain chemical Catalase. Decomposition of hydrogen Furthermore, in accordance with the reactions; this high degree of specificity peroxide (H2O2), yielding water and September 20, 1993, Federal Register and strong catalytic activity are the most notice, FDA’s determination of the 2 In general, proteolytic enzymes are not GRAS status of the enzyme preparation 1 A conjugated protein is a protein that contains sufficiently defined to apply short systematic malt includes only the enzyme a nonamino acid moiety such as a carbohydrate. names. 32906 Federal Register / Vol. 60, No. 122 / Monday, June 26, 1995 / Rules and Regulations

molecular oxygen (H2O2:H2O2 from animal or plant sources. They document, as well as their Chemical , EC 1.11.1.6). contain one or more active enzymes and Abstracts Service Registry Numbers C. Enzyme Preparations That Are the may also contain diluents, (CAS Reg. Nos.) and EC numbers as Subject of This Document preservatives, antioxidants, and other appropriate (Refs. 3, 4, and 9 through substances. Table 1 includes 11). 1. Introduction characterizing enzyme activities 3 of the The enzyme preparations that are the animal- and plant-derived enzyme subject of this document are derived preparations that are the subject of this

TABLE 1.ÐENZYME ACTIVITIES, CAS REG. NOS., AND EC NUMBERS ASSOCIATED WITH SOME ENZYME PREPARATIONS

CAS Reg. Enzyme preparation Enzyme activity No. EC No.

Catalase ...... Catalase ...... 9001±05±2 1.11.1.6 Animal lipase ...... Lipase ...... 9001±62±1 3.1.1.3 Pepsin ...... Protease ...... 9001±75±6 3.4.23.1 Trypsin ...... Protease ...... 9002±07±7 3.4.21.4 Pancreatin 1 ...... Protease ...... 8049±47±6 N/A Amylase Lipase Bromelain ...... Protease ...... 9001±00±7 3.4.22.32 Ficin ...... Protease ...... 9001±33±6 3.4.22.3 Malt 2 ...... α-amylase ...... N/A 3.2.1.1 β-amylase ...... 3.2.1.2 1 Pancreatin is identified by a CAS Reg. No. but does not have an EC number. 2 The α-amylase and β-amylase enzyme activities in malt are identified by EC number, but malt does not have a CAS Reg. No.

2. Animal-Derived Enzyme Preparations 4). These source materials for bovine aqueous extract method, the enzyme a. Sources. The animal-derived liver catalase, animal lipase, pepsin, preparation may remain in aqueous enzyme preparations that are the subject trypsin, and pancreatin were described solution, or it can be precipitated by of this document are derived from a by Tauber in 1949 (Ref. 12) and by Reed, adding a solvent such as acetone or variety of animal sources. Catalase is in Kirk and Othmer in 1957 (Ref. 13). methyl alcohol. For example, pepsin obtained from bovine liver (Ref. 9). b. Methods of manufacture. The can be prepared by the aqueous Animal lipase is obtained from the animal-derived enzyme preparations extraction of animal tissue, while edible forestomach tissue of calves, that are the subject of this document are animal lipase can be prepared by the kids, or lambs, or from animal produced either as tissue preparations tissue preparation method as well as the pancreatic tissue (Ref. 9). Pepsin is (powders) or aqueous extracts of tissues aqueous extraction method. obtained from the glandular layer of hog from edible animals (Refs. 8, 9, 12, and c. Technical effects. Pre-1958 uses in (Ref. 9). Trypsin is obtained 13). In the tissue preparation method, food of animal-derived enzyme from porcine or bovine pancreas (Ref. the animal tissue is ground with preparations are listed in Table 2, using 9). Pancreatin is also obtained from processing aids, such as sodium terminology from the cited reference(s) porcine or bovine pancreas (Refs. 3 and chloride and skim powder. In the published before or during 1958.

TABLE 2.ÐAPPLICATIONS OF ANIMAL-DERIVED ENZYMES IN FOOD PRIOR TO 1958

Technical effect or industry Enzyme preparation Enzyme activity Food categories application References

Pepsin ...... Protease ...... Beer ...... Chillproofing ...... 7, 13, 14, 15 Condiments ...... Not reported ...... 15 Evaporated milk ...... Stabilization ...... 15 Pancreatin ...... Protease ...... Milk ...... Prevention of oxidation flavor 13, 15 Milk ...... Protein hydrolysis ...... 13, 15 Evaporated milk ...... Stabilization ...... 15 Trypsin ...... Protease ...... Milk ...... Antioxidant ...... 16 Lipase ...... Lipase ...... Italian type ...... Flavor production ...... 13, 17, 18 Catalase ...... Catalase ...... Milk ...... Removal of peroxide after 13, 15 sterilization.

3. Plant-Derived Enzyme Preparations and A. bracteatus L. (Ref. 9). Ficin is germination (Ref. 19). These source obtained from the latex of species of the materials for bromelain, ficin, and malt a. Sources. Bromelain is obtained genus Ficus (fig tree) (Ref. 9). Malt is were described by Tauber in 1949 (Ref. from the pineapples Ananas comosus obtained from barley after controlled 12) and by Reed in 1957 (Ref. 13).

3 The activity of a commercial product is a units per unit weight of the product (Ref. 8). The measurement of the rate of the reaction catalyzed enzyme preparation is then diluted or concentrated by the enzyme of interest in the enzyme until the activity is within a certain desired range. preparation, and is usually expressed in activity Federal Register / Vol. 60, No. 122 / Monday, June 26, 1995 / Rules and Regulations 32907

b. Methods of manufacture. Malt is produced from germinated are removed from the extract, which is Bromelain is obtained from pineapple barley. The petition describes the concentrated, stabilized, and juice (pressed from the stems of following process for the manufacture of standardized. The resultant syrup is pineapples that remain after harvesting malt (Ref. 19). Barley is softened by a usually a brown, sweet, and viscous the fruit) by precipitation with alcohol series of steeping operations in water at liquid with a specific gravity of or ammonium sulfate (Refs. 8, 12, and 10 °C to 30 °C until the moisture content approximately 1.1 to 1.3 at 25 °C. 13). Ficin is obtained from the latex of of the kernels reaches 40 to 50 percent. c. Technical effects. Pre-1958 uses in a variety of tropical fig trees by The is then germinated under food of plant-derived enzyme precipitation with acetone or alcohol controlled conditions for a period of up preparations are listed in Table 3, using (Refs. 9, 12, and 14). to 7 days. Reducing substances are terminology from the cited reference(s) added to activate the enzymes. Solids published before or during 1958.

TABLE 3.ÐAPPLICATIONS OF PLANT-DERIVED ENZYMES IN FOOD PRIOR TO 1958

Technical effect or industry Enzyme preparation Enzyme activity Food categories application References

Malt ...... Amylase ...... Bread ...... Baking ...... 7, 14, 15 Beer ...... Mashing ...... 14, 15 Precooked baby cereals ...... Not reported ...... 15 Breakfast cereals ...... Not reported ...... 14, 15 Distilled beverages ...... Mashing ...... 15 Bromelain ...... Protease ...... Beer ...... Chillproofing ...... 13, 14, 15 Condiments ...... Not reported ...... 15 Milk ...... Protein hydrolysis ...... 15 Evaporated milk ...... Stabilization ...... 15 Meat ...... Tenderizing, softening tissue 13, 14, 15, 20 Sausage casings ...... Tenderizing ...... 14, 15 Fish ...... Condensing fish solubles ...... 15 Ficin ...... Protease ...... Meat ...... Softening ...... 20

IV. Safety Evaluation fresh fruits and and are not diphtheria toxin and certain enzymes in inactivated unless the fruits or the venom of poisonous snakes) catalyze A. Pre-1958 History of Use in Food vegetables are cooked (Refs. 6 and 21). unusual reactions that are not related to Enzymes have been used for many The enzymes that are the subject of the types of catalysis that are common years in the production and processing this document are naturally occurring in food processing and that are the of food, for example, in the baking, proteins that are ubiquitous in living subject of this document. Further, the dairy, and brewing industries (e.g., see organisms. They are derived from agency has recently noted, in the Refs. 7, 13, and 14). The consumption animals and plants that have been used context of guidance to industry of food produced using these enzymes as sources of food, and are identical or regarding the safety assessment of new has produced no evidence of an substantially similar 4 to enzymes that plant varieties, that newly introduced associated human health hazard. have been safely consumed as part of enzymes do not generally raise safety The petitioner provided generally the diet throughout human history. concerns (Ref. 22). Exceptions include available information, including Issues relevant to a safety evaluation enzymes that produce substances that published papers and review articles, of proteins from food sources are are not ordinarily digested and showing that the animal- and plant- potential toxicity and allergenicity. metabolized, or that produce toxic derived enzyme preparations that are Pariza and Foster (Ref. 6) note that very substances. The functions of the the subject of this document were few toxic agents have enzymatic enzymes that are the subject of this commonly used in food prior to 1958. properties, and those that do (e.g., document are well known; they split For example, the pre-1958 food uses proteins, carbohydrates, lipids, or other shown in Tables 2 and 3 were 4 Enzymes that have the same function and that substances (e.g., hydrogen peroxide) are identified by the same name and EC number documented in articles that were into smaller subunits that do not have published in or before 1958; the cited often differ slightly in structure and properties when they are obtained from different sources. For toxic properties and that are readily references demonstrate that the use of example, the structure of an enzyme isolated from metabolized by the human body. these enzyme preparations in a variety one tissue (such as the liver) of one animal species, The agency is not aware of any reports of foods was widely recognized by 1958. may differ slightly from that of the same enzyme isolated from a different tissue from the same of allergic reactions associated with the Therefore, the agency concludes that the species, or from the liver of another animal species. ingestion in food of the enzymes that are enzyme preparations that are the subject In part because of this variability, the diet routinely the subject of this document. There have of this document were in common use contains many thousands of different enzyme been, however, some reports of allergies in food prior to January 1, 1958. protein molecules. The concept of substantial similarity relative to food safety assessment has and primary irritations from skin B. Corroborating Evidence of Safety recently been discussed by several expert groups. contact with enzymes or inhalation of For example, a report prepared by an expert group dust from concentrated enzymes (for 1. The Enzyme Components of the Organization for Economic Co-operation and Development (OECD) concluded, in part, ‘‘[I]f a new example, proteases used in the A wide variety of enzymes has always food or food component is found to be substantially manufacture of laundry detergents) been present in human food. Moreover, equivalent to an existing food or food component, (Refs. 23 through 25). These reports many naturally occurring enzymes in it can be treated in the same manner with respect relate primarily to workers in to safety. No additional safety concerns would be the cells of animals and plants used for expected.’’ (‘‘Safety Evaluation of Foods Derived by production plants (Ref. 24) and are not food remain active after cell death. For Modern Biotechnology: Concepts and Principles,’’ relevant to an evaluation of the safety of example, active enzymes are present in OECD, 1993, Paris). ingestion of such enzymes in food. 32908 Federal Register / Vol. 60, No. 122 / Monday, June 26, 1995 / Rules and Regulations

Moreover, Pariza and Foster (Ref. 6) when produced in accordance with about hazards inherent in their use. The note that there are no confirmed reports CGMP, the plant material used in the comment stated that enzyme of primary irritations in consumers production of enzymes consists of preparations are rarely purified to any caused by enzymes used in food components that leave no residues significant degree and contain a variety processing. harmful to health in the finished food of cellular constituents and metabolic The 1977 report of the Select under normal conditions of use (Ref. 9). debris. The comment further argued Committee on GRAS substances The enzyme preparations may contain that, although enzyme preparations are concerning the plant enzyme papain substances, such as salts, preservatives, used at low levels and are inactivated (Ref. 23) supports the view that the or stabilizers, that are used in their after the treatment of food, they may ingestion of an active protease at levels preparation and purification. When elicit allergic reactions and other found in food products is not likely to used in accordance with CGMP, these biological activities which could be affect the human , processing aids are substances that are detrimental to human health. In support where many proteases already exist at acceptable for general use in foods (Ref. of this statement, the comment cited a levels adequate to digest food: 9). As always, any of these substances published scientific article (Ref. 26) In common with other proteolytic that are intended to become or become which reported that enzyme enzymes, papain digests the mucosa and functional components of the enzyme preparations from B. subtilis caused musculature of tissues in contact with the preparation must be GRAS substances temporary weight loss and aggravated active enzyme for an appreciable period. or food additives approved for use in infection in mice when injected into the Because there is no food use of papain that the manufacture of enzyme abdominal cavity and caused hemolysis could result in the enzyme preparation preparations. Therefore, the agency and hemagglutination of occurring in sufficient amount in foods to concludes that the presence of added erythrocytes in in vitro studies. Because produce these effects, this property does not substances and impurities derived from pose a dietary hazard. this article concerns microbially derived the enzyme source or introduced by enzyme preparations injected directly In summary, the enzyme components manufacturing does not present a basis into the abdominal cavity, it is not of the preparations that are the subject for concern about the safety of the relevant to this rulemaking, which of this document are identical or enzyme preparations. concerns animal- and plant-derived substantially similar to enzymes that are 3. Dietary Exposure enzyme preparations consumed by known to have been safely consumed in mouth. the diet; they do not result in the Because enzymes are highly efficient The agency also notes that under production of toxic substances; and catalysts, they are needed in only certain circumstances, applicable their use in food for many years has not minute quantities to perform their regulations already require use of an been associated with reports of function. When used in accordance with enzyme preparation in a food to be allergenicity or primary irritation. CGMP, the amounts added to food declared on the label, depending upon Therefore, the agency finds that the represent only a minute fraction of the the nature of the enzyme preparation’s presence of the enzyme components total food mass. The history of common use and technical effect in the food. does not create a basis for concern about use in food for many years of the These regulatory requirements are the safety of the enzyme preparations. enzyme preparations that are the subject discussed below. of this document has produced no The Federal Food, Drug, and Cosmetic 2. Enzyme Sources and Processing Aids evidence of an associated hazard; Act (21 U.S.C. 343(i)(2)) requires that all The agency has concluded that the further, there is no reason to believe that ingredients of multi-ingredient foods be enzyme components of enzyme use of these enzyme preparations at listed on the label of the food. By preparations do not raise safety levels needed to perform their functions regulation, FDA has exempted certain concerns; therefore, the relevant safety would raise a safety concern. Therefore, ingredients that are used only as issue becomes whether the enzyme the agency concludes that no limits processing aids from this requirement. preparations contain toxic other than CGMP are needed to ensure Sections 101.100(a)(3)(ii)(a) and contaminants. Enzyme preparations safe use. (a)(3)(ii)(c) (21 CFR 101.100(a)(3)(ii)(a) used in food processing are usually not and (a)(3)(ii)(c)) provide an exemption chemically pure but contain, in addition V. Comments from the ingredient listing requirement to the enzyme component, materials FDA received seven letters in for processing aids that are added to a that derive from the enzyme source, as response to the filing notice and none in food for their technical or functional well as from the manufacturing methods response to the amendment notices. effect during processing, but are either used to generate the finished enzyme Three comments concerned microbially removed from the food before packaging preparation. derived enzyme preparations, which or are present in the finished food at In accordance with § 170.30(h)(1), the will be addressed in a separate insignificant levels and do not have any enzyme preparations affirmed as GRAS document. Of the remaining four technical or functional effect in the in this document must comply with the comments, one came from a food finished food. Although many enzyme general requirements and additional manufacturer, two from trade preparations are used as processing aids requirements for enzyme preparations associations, and one from a consumer in food (e.g., the use of amylase in the Food Chemicals Codex, 3d ed. group. Three comments supported the preparations in the manufacture of (Ref. 9). When the animal-derived petition for GRAS affirmation of the glucose syrup and the use of protease enzyme preparations that are the subject enzyme preparations included in the preparations in the manufacture of of this document are produced in petition, stating that these enzyme protein hydrolyzates), other enzyme accordance with current good preparations have a long history of use preparations are not used solely as manufacturing practice (CGMP), they in foods such as , bread, and corn processing aids in the manufacture of are obtained from animal tissues that syrup. foods (e.g., the use of lipase comply with applicable Federal meat One comment asserted that enzyme preparations for flavor production in inspection requirements and that are preparations should not be considered cheeses and the use of protease handled in accordance with good GRAS, and their use should be declared preparations in tenderizing meat). In hygienic practices (Ref. 9). Similarly, on the label of foods to warn consumers these cases, the enzymes remain active Federal Register / Vol. 60, No. 122 / Monday, June 26, 1995 / Rules and Regulations 32909 in the finished food product, no limits other than CGMP (21 CFR substances. Compliance costs to firms functioning as an integral part of the 184.1(b)(1)). The agency further are therefore estimated to be zero. The food by enhancing body, flavor, and concludes that the general and substances that are the subject of this aroma (49 FR 29242, July 19, 1984). additional requirements for enzyme document pose no health risks to Because such effects in the finished preparations in the Food Chemicals consumers when used as intended. food remove the enzymes from the Codex, 3d ed. (1981), pp. 107–110, are Costs to consumers are therefore also ingredient listing exemption in adequate as minimum criteria for food- estimated to be zero. § 101.100(a)(3)(ii)(c), the use of such grade preparations of these enzymes. enzymes must be declared on the label. To clarify the identity of each enzyme In accordance with the Regulatory Therefore, whether a label declaration is preparation, the agency is including in Flexibility Act, FDA also has needed for the use of an enzyme §§ 184.1024(a), 184.1034(a), 184.1316(a), determined that this final rule will not preparation in a food will depend upon 184.1415(a), 184.1443a(a), 184.1583(a), have a significant adverse impact on a its function and effect in the food. 184.1595(a), and 184.1914(a), the EC substantial number of small businesses. number(s) of the enzyme preparation or IX. References VI. Conclusions of the characterizing enzyme The petitioner has provided generally activity(ies) for food use of the The following references have been available evidence demonstrating that preparation 5. In order to make clear that placed on display in the Dockets the enzyme preparations under the affirmation of the GRAS status of Management Branch (address above) consideration were in common use in these enzyme preparations is based on and may be seen by interested persons food prior to 1958. As provided for the evaluation of specific uses, the between 9 a.m. and 4 p.m., Monday under § 170.30(a) and (c)(1), FDA has agency is including in §§ 184.1024(c), through Friday. determined that this information 184.1034(c), 184.1316(c), 184.1415(c), provides an adequate basis upon which 184.1443a(c), 184.1583(c), 184.1595(c), 1. Comments of Ad Hoc Enzyme Technical to conclude that the use of these enzyme and 184.1914(c) the technical effect and Committee regarding FDA’s draft final preparations in food is generally the specific substances on which each regulations, entitled ‘‘Enzymes Proposed recognized as safe among the enzyme preparation acts, although the for Affirmation as GRAS,’’ with a letter community of experts qualified by data show no basis for a potential risk dated December 21, 1984, from Roger D. scientific training and experience to Middlekauff, Ad Hoc Enzyme Technical from any foreseeable use of these Committee, to Kenneth A. Falci, FDA. evaluate the safety of food ingredients. enzyme preparations. 2. Letter dated September 20, 1985, from This evidence of common use in food VII. Environmental Impact Roger D. Middlekauff, Enzyme Technical prior to 1958 without any reported Association, to Lawrence J. Lin, FDA. adverse effects from consumption is The agency has determined under 21 3. Monograph on ‘‘Pancreatin,’’ U.S. corroborated by the absence of any CFR 25.24(b)(7) that this action is of a Pharmacopeia, 21st revision, the United reports of toxicity resulting from use of type that does not individually or States Pharmacopeial Convention, Inc., the enzyme preparations in food since cumulatively have a significant effect on Rockville, MD, pp. 777–778, 1985. 1958, by information that the enzymes the human environment. Therefore, 4. Monograph on ‘‘Pancreatin,’’ U.S. themselves and the sources from which neither an environmental assessment Pharmacopeia, 6th supp., the United they are derived are nontoxic, and by nor an environmental impact statement States Pharmacopeial Convention, Inc., evidence that manufacturing will not is required. Rockville, MD, pp. 2595–2597, 1987. introduce impurities that will adversely 5. Morris, W., editor, The American Heritage VIII. Economic Impact affect the safety of the finished enzyme Dictionary of the English Language, preparations. Moreover, the enzyme FDA has examined the impact of this Houghton Mifflin Co., Boston, MA, p. 438, 1976. preparations that are the subject of this final rule affirming the GRAS status of 6. Pariza, M. W., and E. M. Foster, document are substantially similar to enzyme preparations from animal and plant sources under Executive Order ‘‘Determining the Safety of Enzymes enzymes naturally present in foods that Used in Food Processing,’’ Journal of have been safely consumed in the 12866 and the Regulatory Flexibility Act Food Protection, 46:453–468, 1983. human diet for centuries. (Pub. L. 96–354). Executive Order 12866 7. Reed, G., ‘‘Industrial Enzymes—Now Having evaluated the information in directs Federal agencies to assess the Speed Natural Processes,’’ Food the petition, along with other available costs and benefits of available regulatory Engineering, 24:105–109, 1952. information that related to the use of alternatives and, when regulation is 8. Scott, D., ‘‘Enzymes, Industrial,’’ these enzyme preparations, the agency necessary, to select regulatory Encyclopedia of Chemical Technology, concludes that the following enzyme approaches that maximize net benefits Mark, H. F. et al., editors, John Wiley preparations derived from animal or (including potential economic, and Sons, New York, 3d ed., 9:173–224, plant sources are GRAS under environmental, public health and safety 1978. conditions of use consistent with effects; distributive impacts; and 9. Monograph on ‘‘Enzyme Preparations,’’ Food Chemicals Codex, National CGMP: Bromelain, catalase (bovine equity). The Regulatory Flexibility Act requires Federal agencies to minimize Academy Press, Washington, DC, 3d ed., liver), ficin, animal lipase, malt, pp. 107–110, and 480–481, 1981. the economic impact of their regulations pancreatin (as a source of protease 10. IUB, ‘‘Enzyme Nomenclature 1992,’’ activity), pepsin, and trypsin. The on small businesses. Academic Press, New York, pp. 116, 307, agency is basing its conclusion on The agency finds that this final rule 346, 388, 399, 402–403, 1992. evidence of a substantial history of safe is not a significant regulatory action as 11. IUB, ‘‘Enzyme Nomenclature 1964,’’ consumption of the enzyme defined by Executive Order 12866. The Academic Press, New York, pp. 66–67, preparations in food by a significant rule requires no change in current 86–87, 126–131, 136–149, and 170–171, number of consumers prior to 1958, industry practice concerning the 1965. corroborated by the other evidence manufacture and use of these 12. Tauber, H., ‘‘The Chemistry and summarized above. Technology of Enzymes,’’ John Wiley FDA is therefore affirming that the use 5 The EC number is sufficient to define the and Sons, New York, pp. 25–26, 130– characterizing activity in the enzyme preparation. 131, 140, 145–151, 163–167, 192–193, of the enzyme preparations that are the Therefore, FDA is not including the EC systematic and 327–335, 1949. subject of this document is GRAS with name in the regulation. 32910 Federal Register / Vol. 60, No. 122 / Monday, June 26, 1995 / Rules and Regulations

13. Reed, G., ‘‘Enzymes, Industrial,’’ List of Subjects in 21 CFR Part 184 bovine liver. It is a partially purified Encyclopedia of Chemical Technology, Food ingredients, Incorporation by liquid or powder. Its characterizing Kirk, R. E. and D. F. Othmer, editors, enzyme activity is catalase (EC 1.11.1.6). Interscience Encyclopedia, Inc., New reference. Therefore, under the Federal Food, (b) The ingredient meets the general York, 1st supplemental vol., pp. 294– requirements and additional 312, 1957. Drug, and Cosmetic Act and under requirements for enzyme preparations 14. Underkofler, L. A., and W. J. Ferracone, authority delegated to the Commissioner ‘‘Commercial Enzymes—Potent of Food and Drugs and redelegated to in the Food Chemicals Codex, 3d ed. Catalyzers that Promote Quality,’’ Food the Director, Center for Food Safety and (1981), p. 110, which is incorporated by Engineering, 29:123, 125–126, 130, and Applied Nutrition, 21 CFR part 184 is reference in accordance with 5 U.S.C. 133, 1957. amended as follows: 552(a) and 1 CFR part 51. Copies are 15. Underkofler, L. A., R. R. Barton, and S. available from the National Academy S. Rennet, ‘‘Microbiological Process PART 184ÐDIRECT FOOD Press, 2101 Constitution Ave., NW., Report—Production of Microbial SUBSTANCES AFFIRMED AS Washington, DC 20418, or may be Enzymes and Their Applications,’’ GENERALLY RECOGNIZED AS SAFE examined at the Office of Premarket Applied Microbiology, 6:212–221, 1958. Approval (HFS–200), Food and Drug 16. Smythe, C. V., ‘‘Microbiological 1. The authority citation for 21 CFR Administration, 200 C St., SW., Production of Enzymes and Their part 184 continues to read as follows: Practical Applications,’’ Economic Washington, DC, and the Office of the Botany, 5:126–144, 1951. Authority: Secs. 201, 402, 409, 701 of the Federal Register, 800 North Capitol St. Federal Food, Drug, and Cosmetic Act (21 17. Harper, W. J. and J. E. Long, ‘‘Italian NW., suite 700, Washington, DC. U.S.C. 321, 342, 348, 371). . IV. Various Free (c) In accordance with § 184.1(b)(1), Amino and Fatty Acids in Commercial 2. Section 184.1024 is added to the ingredient is used in food with no Provolone Cheese,’’ Journal of Dairy subpart B to read as follows: limitation other than current good Science, 39:129–137, 1956. manufacturing practice. The affirmation 18. Long, J. E., and W. J. Harper, ‘‘Italian § 184.1024 Bromelain. of this ingredient as GRAS as a direct Cheese Ripening. VI. Effects of Different (a) Bromelain (CAS Reg. No. 9001– food ingredient is based upon the Types of Lipolytic Enzyme Preparations 00–7) is an enzyme preparation derived following current good manufacturing on the Accumulation of Various Free from the pineapples Ananas comosus practice conditions of use: Fatty and Free Amino Acids and the and A. bracteatus L. It is a white to light (1) The ingredient is used as an Development of Flavor in Provolone and tan amorphous powder. Its enzyme as defined in § 170.3(o)(9) of Romano Cheese,’’ Journal of Dairy Science, 39:245–252, 1956. characterizing enzyme activity is that of this chapter to decompose hydrogen 19. Response of the Enzyme Technical a peptide (EC 3.4.22.32). peroxide. Association to the letter dated June 26, (b) The ingredient meets the general (2) The ingredient is used in food at 1986, of Lawrence J. Lin regarding requirements and additional levels not to exceed current good GRASP 3G0016, received with a letter requirements for enzyme preparations manufacturing practice. dated October 3, 1986, from Roger D. in the Food Chemicals Codex, 3d ed. 4. Section 184.1316 is added to Middlekauff of the Enzyme Technical (1981), p. 110, which is incorporated by subpart B to read as follows: Association, to Lawrence J. Lin, FDA. reference in accordance with 5 U.S.C. § 184.1316 Ficin. 20. ‘‘List of Chemicals Approved Under Meat 552(a) and 1 CFR part 51. Copies are Inspection Act Before September 6, 1958, available from the National Academy (a) Ficin (CAS Reg. No. 9001–33–6) is Which are Exempted from the 1958 Food Press, 2101 Constitution Ave. NW., an enzyme preparation obtained from Additives Amendment of the Federal the latex of species of the genus Ficus, Food, Drug, and Cosmetic Act,’’ Food Washington, DC, or may be examined at the Office of Premarket Approval (HFS– which include a variety of tropical fig Drug Cosmetic Law Journal, 13:834–840, trees. It is a white to off-white powder. 1958. 200), Food and Drug Administration, Its characterizing enzyme activity is that 21. De Becze, G. I., ‘‘Food Enzymes,’’ Critical 200 C St. SW., Washington, DC, and the Reviews in Food Technology,’’ 1:479– Office of the Federal Register, 800 North of a peptide hydrolase (EC 3.4.22.3). 518, 1970. Capitol St. NW., suite 700, Washington, (b) The ingredient meets the general 22. FDA, ‘‘Statement of Policy: Foods DC. requirements and additional Derived from New Plant Varieties,’’ 57 (c) In accordance with § 184.1(b)(1), requirements for enzyme preparations FR 22984 at 23005; May 29, 1992. the ingredient is used in food with no in the Food Chemicals Codex, 3d ed. 23. ‘‘Evaluation of the Health Aspects of limitation other than current good (1981), p. 110, which is incorporated by Papain as a Food Ingredient,’’ Select manufacturing practice. The affirmation reference in accordance with 5 U.S.C. Committee on GRAS Substances, of this ingredient as GRAS as a direct 552(a) and 1 CFR part 51. Copies are Washington, DC, available through U.S. food ingredient is based upon the available from the National Academy Department of Commerce, National Press, 2101 Constitution Ave., NW., Technical Information Service, Order following current good manufacturing practice conditions of use: Washington, DC 20418, or may be No. PB–274–174, 1977. examined at the Office of Premarket 24. Fulwiler, R. D., ‘‘Detergent Enzymes—An (1) The ingredient is used as an Industrial Hygiene Challenge,’’ enzyme as defined in § 170.3(o)(9) of Approval (HFS–200), Food and Drug American Industrial Hygiene Association this chapter to hydrolyze proteins or Administration, 200 C St., SW., Journal, 32:73–81, 1971. polypeptides. Washington, DC, and the Office of the 25. ‘‘Enzyme-containing Laundering (2) The ingredient is used in food at Federal Register, 800 North Capitol St., Compounds and Consumer Health,’’ levels not to exceed current good NW., suite 700, Washington, DC. National Research Council/National manufacturing practice. (c) In accordance with § 184.1(b)(1), Academy of Sciences, National 3. Section 184.1034 is added to the ingredient is used in food with no Technical Information Service, subpart B to read as follows: limitation other than current good Washington, DC, Order No. PB–204–118, manufacturing practice. The affirmation 1971. § 184.1034 Catalase (bovine liver). of this ingredient as GRAS as a direct 26. Dubos, R., ‘‘Toxic Factors in Enzymes (a) Catalase (bovine liver) (CAS Reg. food ingredient is based upon the Used in Laundry Products,’’ Science, No. 9001–05–2) is an enzyme following current good manufacturing 173:259–260, 1971. preparation obtained from extracts of practice conditions of use: Federal Register / Vol. 60, No. 122 / Monday, June 26, 1995 / Rules and Regulations 32911

(1) The ingredient is used as an reference in accordance with 5 U.S.C. § 184.1595 Pepsin. enzyme as defined in § 170.3(o)(9) of 552(a) and 1 CFR part 51. Copies are (a) Pepsin (CAS Reg. No. 9001–75–6) this chapter to hydrolyze proteins or available from the National Academy is an enzyme preparation obtained from polypeptides. Press, 2101 Constitution Ave., NW., the glandular layer of hog stomach. It is (2) The ingredient is used in food at Washington, DC 20418, or may be a white to light tan powder, amber levels not to exceed current good examined at the Office of Premarket paste, or clear amber to brown liquid. Its manufacturing practice. Approval (HFS–200), Food and Drug characterizing enzyme activity is that of 5. Section 184.1415 is added to Administration, 200 C St., SW., a peptide hydrolase (EC 3.4.23.1). subpart B to read as follows: Washington, DC, and the Office of the (b) The ingredient meets the general Federal Register, 800 North Capitol St., requirements and additional § 184.1415 Animal lipase. NW., suite 700, Washington, DC. requirements for enzyme preparations (a) Animal lipase (CAS Reg. No. (c) In accordance with § 184.1(b)(1), in the Food Chemicals Codex, 3d ed. 9001–62–1) is an enzyme preparation the ingredient is used in food with no (1981), p. 110, which is incorporated by obtained from edible forestomach tissue limitation other than current good reference in accordance with 5 U.S.C. of calves, kids, or lambs, or from animal manufacturing practice. The affirmation 552(a) and 1 CFR part 51. Copies are pancreatic tissue. The enzyme of this ingredient as GRAS as a direct available from the National Academy preparation may be produced as a tissue food ingredient is based upon the Press, 2101 Constitution Ave. NW., preparation or as an aqueous extract. Its following current good manufacturing Washington, DC 20418, or may be characterizing enzyme activity is that of practice conditions of use: examined at the Office of Premarket a triacylglycerol hydrolase (EC 3.1.1.3). (1) The ingredient is used as an Approval (HFS–200), Food and Drug (b) The ingredient meets the general enzyme as defined in § 170.3(o)(9) of Administration, 200 C St. SW., requirements and additional this chapter to hydrolyze starch or Washington, DC, and the Office of the requirements for enzyme preparations starch-derived polysaccharides. Federal Register, 800 North Capitol St. in the Food Chemicals Codex, 3d ed. (2) The ingredient is used in food at NW., suite 700, Washington, DC. (1981), p. 110, which is incorporated by levels not to exceed current good (c) In accordance with § 184.1(b)(1), reference in accordance with 5 U.S.C. manufacturing practice. the ingredient is used in food with no 552(a) and 1 CFR part 51. Copies are 7. Section 184.1583 is added to limitation other than current good available from the National Academy subpart B to read as follows: manufacturing practice. The affirmation Press, 2101 Constitution Ave., NW., of this ingredient as GRAS as a direct § 184.1583 Pancreatin. Washington, DC 20418, or may be food ingredient is based upon the examined at the Office of Premarket (a) Pancreatin (CAS Reg. No. 8049– following current good manufacturing Approval (HFS–200), Food and Drug 47–6) is an enzyme preparation practice conditions of use: Administration, 200 C St., SW., obtained from porcine or bovine (1) The ingredient is used as an Washington, DC, and the Office of the pancreatic tissue. It is a white to tan enzyme as defined in § 170.3(o)(9) of Federal Register, 800 North Capitol St., powder. Its characterizing enzyme this chapter to hydrolyze proteins or NW., suite 700, Washington, DC. activity that of a peptide hydrolase (EC polypeptides. (c) In accordance with § 184.1(b)(1), 3.4.21.36). (2) The ingredient is used in food at the ingredient is used in food with no (b) The ingredient meets the general levels not to exceed current good limitation other than current good requirements and additional manufacturing practice. manufacturing practice. The affirmation requirements in the Food Chemicals 9. Section 184.1914 is added to of this ingredient as GRAS as a direct Codex, 3d ed. (1981), p. 110, which is subpart B to read as follows: food ingredient is based upon the incorporated by reference in accordance following current good manufacturing with 5 U.S.C. 552(a) and 1 CFR part 51. § 184.1914 Trypsin. practice conditions of use: Copies are available from the National (a) Trypsin (CAS Reg. No. 9002–07–7) (1) The ingredient is used as an Academy Press, 2101 Constitution Ave. is an enzyme preparation obtained from enzyme as defined in § 170.3(o)(9) of NW., Washington, DC 20418, or may be purified extracts of porcine or bovine this chapter to hydrolyze fatty acid examined at the Office of Premarket pancreas. It is a white to tan amorphous glycerides. Approval (HFS–200), Food and Drug powder. Its characterizing enzyme (2) The ingredient is used in food at Administration, 200 C St. SW., activity is that of a peptide hydrolase levels not to exceed current good Washington, DC, and the Office of the (EC 3.4.21.4). manufacturing practice. Federal Register, 800 North Capitol St. (b) The ingredient meets the general 6. Section 184.1443a is added to NW., suite 700, Washington, DC. requirements and additional subpart B to read as follows: (c) In accordance with § 184.1(b)(1), requirements for enzyme preparations the ingredient is used in food with no in the Food Chemicals Codex, 3d ed. § 184.1443a Malt. limitation other than current good (1981), p. 110, which is incorporated by (a) Malt is an enzyme preparation manufacturing practice. The affirmation reference in accordance with 5 U.S.C. obtained from barley which has been of this ingredient as GRAS as a direct 552(a) and 1 CFR part 51. Copies are softened by a series of steeping food ingredient is based upon the available from the National Academy operations and germinated under following current good manufacturing Press, 2101 Constitution Ave. NW., controlled conditions. It is a brown, practice conditions of use: Washington, DC 20418, or may be sweet, and viscous liquid or a white to (1) The ingredient is used as an examined at the Office of Premarket tan powder. Its characterizing enzyme enzyme as defined in § 170.3(o)(9) of Approval (HFS–200), Food and Drug activities are α-amylase (EC 3.2.1.1.) and this chapter to hydrolyze proteins or Administration, 200 C St. SW., β-amylase (EC 3.2.1.2). polypeptides. Washington, DC, and the Office of the (b) The ingredient meets the general (2) The ingredient is used in food at Federal Register, 800 North Capitol St. requirements and additional levels not to exceed current good NW., suite 700, Washington, DC. requirements for enzyme preparations manufacturing practice. (c) In accordance with § 184.1(b)(1), in the Food Chemicals Codex, 3d ed. 8. Section 184.1595 is added to the ingredient is used in food with no (1981), p. 110, which is incorporated by subpart B to read as follows: limitation other than current good 32912 Federal Register / Vol. 60, No. 122 / Monday, June 26, 1995 / Rules and Regulations manufacturing practice. The affirmation IASA, Pub. L. 103–382, enacted October Independent Living Services of this ingredient as GRAS as a direct 20, 1994. Section 431 was also Program and Centers for food ingredient is based upon the redesignated as section 437. As a Independent Living Program: following current good manufacturing consequence of the new legislation, General Provisions, State practice conditions of use: regulations of the Department are no Independent Living Services, (1) The ingredient is used as an longer subject to a 45-day delayed Centers for Independent Living, and enzyme as defined in § 170.3(o)(9) of effective date. This notice announces Independent Living Services for this chapter to hydrolyze proteins or the effective dates for those regulations Older Individuals Who Are Blind, polypeptides. subject to the previous statutory published August 15, 1994 (59 FR (2) The ingredient is used in food at requirement for the delayed effective 41908). levels not to exceed current good date. In the future, as a result of the new DATES: Effective date: September 29, manufacturing practice. legislation, it will not be necessary for 1994. Dated: June 14, 1995. the Department to publish a special 9. 34 CFR Part 607, final regulations for Fred. R, Shank, announcement of effective dates. the Strengthening Institutions Director, Center for Food Safety and Applied The effective date provision for each Program, published August 15, Nutrition. of the regulatory documents included in 1994 (59 FR 41914). [FR Doc. 95–15239 Filed 6–23–95; 8:45 am] the notice stated that the effective date DATES: Effective date: September 29, 1994. BILLING CODE 4160±01±P would be announced in a notice published in the Federal Register. 10. 34 CFR Part 647, final regulations for Accordingly, this notice announces the the Ronald E. McNair Postbaccalaureate Achievement DEPARTMENT OF EDUCATION following effective dates: 1. 34 CFR Part 682, final regulations for Program, published August 25, 34 CFR Parts 75, 200, 201, 364, 365, the Federal Family Education Loan 1994 (59 FR 43986). DATES: Effective date: November 7, 366, 367, 386, 388, 396, 403, 405, 406, Program, published May 17, 1994 1994. 607, 641, 647, and 682 (59 FR 25744). 11. 34 CFR Part 396, final regulations for DATES: Effective date: July 1, 1994. Training Interpreters for Individuals Announcement of Effective Dates 2. 34 CFR Part 75, final regulations for Who Are Deaf and Individuals Who Direct Grant Programs, published AGENCY: Department of Education. Are Deaf-Blind, published October June 10, 1994 (59 FR 30258). ACTION: Notice of effective dates. 14, 1994 (59 FR 52218). DATES: Effective date: July 25, 1994. DATES: Effective date: November 28, SUMMARY: Prior to its amendment by the 3. 34 CFR Part 386, final regulations for 1994. Improving America’s Schools Act of Rehabilitation Training: 1994 (IASA), section 431(d) of the Rehabilitation Long-Term Training, Dated: June 21, 1995. General Education Provisions Act published June 16, 1994 (59 FR Judith A. Winston, (GEPA) required that most Department 31060). General Counsel. of Education regulatory documents be DATES: Effective date: July 31, 1994. [FR Doc. 95–15559 Filed 6–23–95; 8:45 am] published in the Federal Register for 4. 34 CFR Part 641, final regulations for BILLING CODE 4000±01±P forty-five (45) calendar days, or longer if the Faculty Development Congress took certain adjournments, Fellowship Program, published July before they became effective. Since 1, 1994 (59 FR 34198). ENVIRONMENTAL PROTECTION future congressional adjournments DATES: Effective date: August 15, AGENCY could not be predicted with certainty 1994. when a document was published, the 5. 34 CFR Parts 403, 405, and 406, final 40 CFR Part 63 Department could not announce a regulations for the State Vocational [AD±FRL±5225±9] specific effective date at the time of and Applied Technology Education publication. This notice announces the Program, National Tech-Prep National Emission Standards for effective dates for certain regulatory Education Program, and State- Hazardous Air Pollutants for Source documents subject to the delayed Administer Tech-Prep Education Categories: Gasoline Distribution effective date requirement of section Program, published July 28, 1994 (Stage I) 431(d) prior to its amendment. (59 FR 38512). DATES: For effective dates, see DATES: Effective date: September 21, AGENCY: Environmental Protection SUPPLEMENTARY INFORMATION. 1994. Agency (EPA). FOR FURTHER INFORMATION CONTACT: 6. 34 CFR Part 388, final regulations for ACTION: Final rule; correction. Kenneth C. Depew, Division of State Vocational Rehabilitation Unit Regulations Management, Office of the In-Service Training, published SUMMARY: This document makes General Counsel, U.S. Department of August 5, 1994 (59 FR 40176). clarifications and corrects errors in the Education, Room 5112, FB–10, 600 DATES: Effective date: September 21, regulatory text of the final rule for Independence Avenue SW., 1994. National Emission Standards for Washington, DC 20202–2241; telephone: 7. 34 CFR Parts 200 and 201, final Gasoline Distribution Facilities (Bulk (202) 401–8300. regulations for the Chapter 1 Gasoline Terminals and Pipeline Individuals who use a Program in Local Educational Breakout Stations) which appeared in telecommunications device for the deaf Agencies and Chapter 1—Migrant the Federal Register on December 14, (TDD) may call the Federal Information Education Program, published 1994 (59 FR 64303). Relay Service (FIRS) at 1–800–877–8339 August 10, 1994 (59 FR 41168). EFFECTIVE DATE: December 14, 1994. between 8 a.m. and 8 p.m., Eastern time, DATES: Effective date: September 24, FOR FURTHER INFORMATION CONTACT: For Monday through Friday. 1994. general and technical information SUPPLEMENTARY INFORMATION: GEPA 8. 34 CFR Parts 364, 365, 366, and 367, concerning the final rule, contact Mr. section 431(d) was amended by the final regulations for State Stephen Shedd, Waste and Chemical