CFR-2000-title21-part 170

21Part 170 to 199Revised as of April 1, 2000

Food and Drugs

Containing a Codification of documentsof general applicability and future effect

As of April 1, 2000

With Ancillaries

Published byOffice of the Federal RegisterNational Archives and RecordsAdministration

As a Special Edition of the Federal Register

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U.S. GOVERNMENT PRINTING OFFICE

WASHINGTON : 2000

For sale by U.S. Government Printing OfficeSuperintendent of Documents, Mail Stop: SSOP, Washington, DC 204029328

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iii

Table of ContentsPage

Explanation ................................................................................................ v

Title 21:

Chapter IFood and Drug Administration, Department of Healthand Human Services (Continued) ................................................. 3

Finding Aids:

Material Approved for Incorporation by Reference ............................ 571

Table of CFR Titles and Chapters ....................................................... 585

Alphabetical List of Agencies Appearing in the CFR ......................... 603

Redesignation Table ............................................................................ 613

List of CFR Sections Affected ............................................................. 615

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iv

Cite this Code: CFR

To cite the regulations inthis volume use title,part and section num-ber. Thus, 21 CFR 170.3refers to title 21, part170, section 3.


vExplanation

The Code of Federal Regulations is a codification of the general and permanentrules published in the Federal Register by the Executive departments and agen-cies of the Federal Government. The Code is divided into 50 titles which representbroad areas subject to Federal regulation. Each title is divided into chapterswhich usually bear the name of the issuing agency. Each chapter is further sub-divided into parts covering specific regulatory areas.

Each volume of the Code is revised at least once each calendar year and issuedon a quarterly basis approximately as follows:

Title 1 through Title 16..............................................................as of January 1Title 17 through Title 27 .................................................................as of April 1Title 28 through Title 41 ..................................................................as of July 1Title 42 through Title 50.............................................................as of October 1

The appropriate revision date is printed on the cover of each volume.

LEGAL STATUS

The contents of the Federal Register are required to be judicially noticed (44U.S.C. 1507). The Code of Federal Regulations is prima facie evidence of the textof the original documents (44 U.S.C. 1510).

HOW TO USE THE CODE OF FEDERAL REGULATIONS

The Code of Federal Regulations is kept up to date by the individual issuesof the Federal Register. These two publications must be used together to deter-mine the latest version of any given rule.

To determine whether a Code volume has been amended since its revision date(in this case, April 1, 2000), consult the ``List of CFR Sections Affected (LSA),''which is issued monthly, and the ``Cumulative List of Parts Affected,'' whichappears in the Reader Aids section of the daily Federal Register. These two listswill identify the Federal Register page number of the latest amendment of anygiven rule.

EFFECTIVE AND EXPIRATION DATES

Each volume of the Code contains amendments published in the Federal Reg-ister since the last revision of that volume of the Code. Source citations forthe regulations are referred to by volume number and page number of the FederalRegister and date of publication. Publication dates and effective dates are usu-ally not the same and care must be exercised by the user in determining theactual effective date. In instances where the effective date is beyond the cut-off date for the Code a note has been inserted to reflect the future effectivedate. In those instances where a regulation published in the Federal Registerstates a date certain for expiration, an appropriate note will be inserted followingthe text.

OMB CONTROL NUMBERS

The Paperwork Reduction Act of 1980 (Pub. L. 96511) requires Federal agenciesto display an OMB control number with their information collection request.


vi

Many agencies have begun publishing numerous OMB control numbers as amend-ments to existing regulations in the CFR. These OMB numbers are placed asclose as possible to the applicable recordkeeping or reporting requirements.

OBSOLETE PROVISIONS

Provisions that become obsolete before the revision date stated on the coverof each volume are not carried. Code users may find the text of provisions ineffect on a given date in the past by using the appropriate numerical list ofsections affected. For the period before January 1, 1986, consult either the Listof CFR Sections Affected, 19491963, 19641972, or 19731985, published in seven sep-arate volumes. For the period beginning January 1, 1986, a ``List of CFR SectionsAffected'' is published at the end of each CFR volume.

INCORPORATION BY REFERENCE

What is incorporation by reference? Incorporation by reference was establishedby statute and allows Federal agencies to meet the requirement to publish regu-lations in the Federal Register by referring to materials already published else-where. For an incorporation to be valid, the Director of the Federal Registermust approve it. The legal effect of incorporation by reference is that the mate-rial is treated as if it were published in full in the Federal Register (5 U.S.C.552(a)). This material, like any other properly issued regulation, has the forceof law.

What is a proper incorporation by reference? The Director of the Federal Registerwill approve an incorporation by reference only when the requirements of 1 CFRpart 51 are met. Some of the elements on which approval is based are:

(a) The incorporation will substantially reduce the volume of material pub-lished in the Federal Register.

(b) The matter incorporated is in fact available to the extent necessary toafford fairness and uniformity in the administrative process.

(c) The incorporating document is drafted and submitted for publication inaccordance with 1 CFR part 51.

Properly approved incorporations by reference in this volume are listed in theFinding Aids at the end of this volume.

What if the material incorporated by reference cannot be found? If you have anyproblem locating or obtaining a copy of material listed in the Finding Aids ofthis volume as an approved incorporation by reference, please contact the agencythat issued the regulation containing that incorporation. If, after contacting theagency, you find the material is not available, please notify the Director of theFederal Register, National Archives and Records Administration, Washington DC20408, or call (202) 5234534.

CFR INDEXES AND TABULAR GUIDES

A subject index to the Code of Federal Regulations is contained in a separatevolume, revised annually as of January 1, entitled CFR INDEX AND FINDING AIDS.This volume contains the Parallel Table of Statutory Authorities and AgencyRules (Table I). A list of CFR titles, chapters, and parts and an alphabeticallist of agencies publishing in the CFR are also included in this volume.

An index to the text of ``Title 3The President'' is carried within that volume.The Federal Register Index is issued monthly in cumulative form. This index

is based on a consolidation of the ``Contents'' entries in the daily Federal Reg-ister.

A List of CFR Sections Affected (LSA) is published monthly, keyed to therevision dates of the 50 CFR titles.


vii

REPUBLICATION OF MATERIAL

There are no restrictions on the republication of material appearing in theCode of Federal Regulations.

INQUIRIES

For a legal interpretation or explanation of any regulation in this volume,contact the issuing agency. The issuing agency's name appears at the top ofoddnumbered pages.

For inquiries concerning CFR reference assistance, call 2025235227 or writeto the Director, Office of the Federal Register, National Archives and RecordsAdministration, Washington, DC 20408.

SALES

The Government Printing Office (GPO) processes all sales and distribution ofthe CFR. For payment by credit card, call 2025121800, MF, 8 a.m. to 4 p.m.e.s.t. or fax your order to 2025122233, 24 hours a day. For payment by check,write to the Superintendent of Documents, Attn: New Orders, P.O. Box 371954,Pittsburgh, PA 152507954. For GPO Customer Service call 2025121803.

ELECTRONIC SERVICES

The full text of the Code of Federal Regulations, the LSA (List of CFR SectionsAffected), The United States Government Manual, the Federal Register, PublicLaws, Weekly Compilation of Presidential Documents and the Privacy Act Com-pilation are available in electronic format at www.access.gpo.gov/nara (``GPO Ac-cess''). For more information, contact Electronic Information DisseminationServices, U.S. Government Printing Office. Phone 2025121530, or 8882936498(tollfree). Email, [email protected].

The Office of the Federal Register also offers a free service on the NationalArchives and Records Administration's (NARA) World Wide Web site for publiclaw numbers, Federal Register finding aids, and related information. Connectto NARA's web site at www.nara.gov/fedreg. The NARA site also contains linksto GPO Access.

RAYMOND A. MOSLEY,

Director,

Office of the Federal Register.

April 1, 2000.


ix

THIS TITLE

Title 21FOOD AND DRUGS is composed of nine volumes. The parts in thesevolumes are arranged in the following order: Parts 199, 100169, 170199, 200299,300499, 500599, 600799, 8001299 and 1300end. The first eight volumes, containingparts 11299, comprise Chapter IFood and Drug Administration, Department ofHealth and Human Services. The ninth volume, containing part 1300 to end, in-cludes Chapter IIDrug Enforcement Administration, Department of Justice, andChapter IIIOffice of National Drug Control Policy. The contents of these vol-umes represent all current regulations codified under this title of the CFR asof April 1, 2000.

Redesignation tables for Chapter IFood and Drug Administration appear inthe Finding Aids section for the volumes containing parts 170199 and 500599.

For this volume, Jonn V. Lilyea was Chief Editor. The Code of Federal Regula-tions publication program is under the direction of Frances D. McDonald, assistedby Alomha S. Morris.


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1Title 21Food andDrugs

(This book contains parts 170 to 199)

Part

CHAPTER IFood and Drug Administration, Department ofHealth and Human Services (Continued) ........................... 170

CROSS REFERENCES: Food Safety and Inspection Service, Department of Agriculture: SeeMeat and Poultry Inspection, 9 CFR chapter III.Federal Trade Commission: See Commercial Practices, 16 CFR chapter I.United States Customs Service, Department of the Treasury: See Customs Duties, 19 CFR

chapter I.Internal Revenue Service, Department of the Treasury: See Internal Revenue, 26 CFR chap-

ter I.Bureau of Alcohol, Tobacco, and Firearms, Department of the Treasury: See Alcohol, To-

bacco Products and Firearms, 27 CFR chapter I.

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3CHAPTER IFOOD AND DRUGADMINISTRATION, DEPARTMENT OF HEALTH

AND HUMAN SERVICES (CONTINUED)(Parts 170 to 199)

EDITORIAL NOTE: The Food and Drug Administration published a document at 49 FR 41019,Oct. 19, 1984, establishing July 1, 1987, as a uniform effective date for compliance for regula-tions affecting the labeling of food products. At 51 FR 34085, Sept. 25, 1986, FDA establishedJanuary 1, 1989 as a new uniform effective date for compliance. The new uniform effectivedate will apply only to final FDA food labeling regulations published after July 1, 1986, andbefore January 1, 1988. At 55 FR 276, Jan. 4, 1990, FDA established January 1, 1993 as a newuniform effective date for compliance. The new uniform effective date will apply only to finalFDA food labeling regulations published after January 1, 1990 and before January 1, 1992.

SUBCHAPTER BFOOD FOR HUMAN CONSUMPTION (CON'T.)

Part Page170 Food additives ......................................................... 5171 Food additive petitions ........................................... 21172 Food additives permitted for direct addition to

food for human consumption ................................ 26173 Secondary direct food additives permitted in food

for human consumption ....................................... 111174 Indirect food additives: General .............................. 140175 Indirect food additives: Adhesives and components

of coatings ............................................................ 141176 Indirect food additives: Paper and paperboard com-

ponents ................................................................. 183177 Indirect food additives: Polymers ........................... 220178 Indirect food additives: Adjuvants, production

aids, and sanitizers ............................................... 339179 Irradiation in the production, processing and han-

dling of food ......................................................... 429180 Food additives permitted in food or in contact

with food on an interim basis pending additionalstudy .................................................................... 435

181 Prior-sanctioned food ingredients ........................... 440182 Substances generally recognized as safe ................. 444184 Direct food substances affirmed as generally recog-

nized as safe ......................................................... 457


421 CFR Ch. I (4100 Edition)

Part Page186 Indirect food substances affirmed as generally rec-

ognized as safe ...................................................... 556189 Substances prohibited from use in human food ...... 561190 Dietary supplements ............................................... 566191199 [Reserved]


5SUBCHAPTER BFOOD FOR HUMAN CONSUMPTION

PART 170FOOD ADDITIVES

Subpart AGeneral Provisions

Sec.170.3 Definitions.170.6 Opinion letters on food additive sta-

tus.170.10 Food additives in standardized foods.170.15 Adoption of regulation on initiative

of Commissioner.170.17 Exemption for investigational use

and procedure for obtaining authoriza-tion to market edible products from ex-perimental animals.

170.18 Tolerances for related food additives.170.19 Pesticide chemicals in processed

foods.

Subpart BFood Additive Safety

170.20 General principles for evaluating thesafety of food additives.

170.22 Safety factors to be considered.170.30 Eligibility for classification as gen-

erally recognized as safe (GRAS).170.35 Affirmation of generally recognized

as safe (GRAS) status.170.38 Determination of food additive sta-

tus.170.39 Threshold of regulation for sub-

stances used in foodcontact articles.

Subpart CSpecific Administrative Rulingsand Decisions

170.45 Fluorine-containing compounds.170.50 Glycine (aminoacetic acid) in food for

human consumption.170.60 Nitrites and/or nitrates in curing pre-

mixes.

AUTHORITY: 21 U.S.C. 321, 341, 342, 346a, 348,371.

SOURCE: 42 FR 14483, Mar. 15, 1977, unlessotherwise noted.


170.3 Definitions.For the purposes of this subchapter,

the following definitions apply:(a) Secretary means the Secretary of

Health and Human Services.(b) Department means the Department

of Health and Human Services.(c) Commissioner means the Commis-

sioner of Food and Drugs.(d) As used in this part, the term act

means the Federal Food, Drug, andCosmetic Act approved June 25, 1936, 52

Stat. 1040 et seq., as amended (21 U.S.C.301392).

(e)(1) Food additives includes all sub-stances not exempted by section 201(s)of the act, the intended use of whichresults or may reasonably be expectedto result, directly or indirectly, eitherin their becoming a component of foodor otherwise affecting the characteris-tics of food. A material used in the pro-duction of containers and packages issubject to the definition if it may rea-sonably be expected to become a com-ponent, or to affect the characteristics,directly or indirectly, of food packed inthe container. ``Affecting the charac-teristics of food'' does not include suchphysical effects, as protecting contentsof packages, preserving shape, and pre-venting moisture loss. If there is nomigration of a packaging componentfrom the package to the food, it doesnot become a component of the foodand thus is not a food additive. A sub-stance that does not become a compo-nent of food, but that is used, for exam-ple, in preparing an ingredient of thefood to give a different flavor, texture,or other characteristic in the food,may be a food additive.

(2) Uses of food additives not requiringa listing regulation. Substances used infood-contact articles (e.g., food-pack-aging and food-processing equipment)that migrate, or may be expected tomigrate, into food at such negligiblelevels that they have been exemptedfrom regulation as food additives under 170.39.

(f) Common use in food means a sub-stantial history of consumption of asubstance for food use by a significantnumber of consumers.

(g) The word substance in the defini-tion of the term ``food additive'' in-cludes a food or food component con-sisting of one or more ingredients.

(h) Scientific procedures include thosehuman, animal, analytical, and otherscientific studies, whether published orunpublished, appropriate to establishthe safety of a substance.

(i) Safe or safety means that there isa reasonable certainty in the minds of


621 CFR Ch. I (4100 Edition) 170.3

competent scientists that the sub-stance is not harmful under the in-tended conditions of use. It is impos-sible in the present state of scientificknowledge to establish with completecertainty the absolute harmlessness ofthe use of any substance. Safety maybe determined by scientific proceduresor by general recognition of safety. Indetermining safety, the following fac-tors shall be considered:

(1) The probable consumption of thesubstance and of any substance formedin or on food because of its use.

(2) The cumulative effect of the sub-stance in the diet, taking into accountany chemically or pharmacologicallyrelated substance or substances in suchdiet.

(3) Safety factors which, in the opin-ion of experts qualified by scientifictraining and experience to evaluate thesafety of food and food ingredients, aregenerally recognized as appropriate.

(j) The term nonperishable processedfood means any processed food not sub-ject to rapid decay or deteriorationthat would render it unfit for consump-tion. Examples are flour, sugar, cere-als, packaged cookies, and crackers.Not included are hermetically sealedfoods or manufactured dairy productsand other processed foods requiring re-frigeration.

(k) General recognition of safety shallbe determined in accordance with 170.30.

(l) Prior sanction means an explicitapproval granted with respect to use ofa substance in food prior to September6, 1958, by the Food and Drug Adminis-tration or the United States Depart-ment of Agriculture pursuant to theFederal Food, Drug, and Cosmetic Act,the Poultry Products Inspection Act,or the Meat Inspection Act.

(m) Food includes human food, sub-stances migrating to food from food-contact articles, pet food, and animalfeed.

(n) The following general food cat-egories are established to group spe-cific related foods together for the pur-pose of establishing tolerances or limi-tations for the use of direct humanfood ingredients. Individual food prod-ucts will be included within these cat-egories according to the detailed clas-sifications lists contained in Exhibit

33B of the report of the National Acad-emy of Sciences/National ResearchCouncil report, ``A Comprehensive Sur-vey of Industry on the Use of FoodChemicals Generally Recognized asSafe'' (September 1972), which is incor-porated by reference. Copies are avail-able from the National Technical Infor-mation Service (NTIS), 5285 Port RoyalRd., Springfield, VA 22161, or availablefor inspection at the Office of the Fed-eral Register, 800 North Capitol Street,NW., suite 700, Washington, DC 20408:

(1) Baked goods and baking mixes, in-cluding all ready-to-eat and ready-to-bake products, flours, and mixes re-quiring preparation before serving.

(2) Beverages, alcoholic, includingmalt beverages, wines, distilled liq-uors, and cocktail mix.

(3) Beverages and beverage bases,nonalcoholic, including only special orspiced teas, soft drinks, coffee sub-stitutes, and fruit and vegetable fla-vored gelatin drinks.

(4) Breakfast cereals, includingready-to-eat and instant and regularhot cereals.

(5) Cheeses, including curd and wheycheeses, cream, natural, grating, proc-essed, spread, dip, and miscellaneouscheeses.

(6) Chewing gum, including all forms.(7) Coffee and tea, including regular,

decaffeinated, and instant types.(8) Condiments and relishes, includ-

ing plain seasoning sauces and spreads,olives, pickles, and relishes, but notspices or herbs.

(9) Confections and frostings, includ-ing candy and flavored frostings,marshmallows, baking chocolate, andbrown, lump, rock, maple, powdered,and raw sugars.

(10) Dairy product analogs, includingnondairy milk, frozen or liquid cream-ers, coffee whiteners, toppings, andother nondairy products.

(11) Egg products, including liquid,frozen, or dried eggs, and egg dishesmade therefrom, i.e., egg roll, egg fooyoung, egg salad, and frozen multi-course egg meals, but not fresh eggs.

(12) Fats and oils, including mar-garine, dressings for salads, butter,salad oils, shortenings and cookingoils.

(13) Fish products, including all pre-pared main dishes, salads, appetizers,


7Food and Drug Administration, HHS 170.3

frozen multicourse meals, and spreadscontaining fish, shellfish, and otheraquatic animals, but not fresh fish.

(14) Fresh eggs, including cookedeggs and egg dishes made only fromfresh shell eggs.

(15) Fresh fish, including only freshand frozen fish, shellfish, and otheraquatic animals.

(16) Fresh fruits and fruit juices, in-cluding only raw fruits, citrus, melons,and berries, and home-prepared ``ades''and punches made therefrom.

(17) Fresh meats, including only freshor home-frozen beef or veal, pork, lambor mutton and home-prepared freshmeat-containing dishes, salads, appe-tizers, or sandwich spreads made there-from.

(18) Fresh poultry, including onlyfresh or home-frozen poultry and gamebirds and home-prepared fresh poultry-containing dishes, salads, appetizers, orsandwich spreads made therefrom.

(19) Fresh vegetables, tomatoes, andpotatoes, including only fresh andhome-prepared vegetables.

(20) Frozen dairy desserts and mixes,including ice cream, ice milks, sher-bets, and other frozen dairy dessertsand specialties.

(21) Fruit and water ices, includingall frozen fruit and water ices.

(22) Gelatins, puddings, and fillings,including flavored gelatin desserts,puddings, custards, parfaits, pie fill-ings, and gelatin base salads.

(23) Grain products and pastas, in-cluding macaroni and noodle products,rice dishes, and frozen multicoursemeals, without meat or vegetables.

(24) Gravies and sauces, including allmeat sauces and gravies, and tomato,milk, buttery, and specialty sauces.

(25) Hard candy and cough drops, in-cluding all hard type candies.

(26) Herbs, seeds, spices, seasonings,blends, extracts, and flavorings, includ-ing all natural and artificial spices,blends, and flavors.

(27) Jams and jellies, home-prepared,including only home-prepared jams,jellies, fruit butters, preserves, andsweet spreads.

(28) Jams and jellies, commercial, in-cluding only commercially processedjams, jellies, fruit butters, preserves,and sweet spreads.

(29) Meat products, including allmeats and meat containing dishes, sal-ads, appetizers, frozen multicoursemeat meals, and sandwich ingredientsprepared by commercial processing orusing commercially processed meatswith home preparation.

(30) Milk, whole and skim, includingonly whole, lowfat, and skim fluidmilks.

(31) Milk products, including flavoredmilks and milk drinks, dry milks, top-pings, snack dips, spreads, weight con-trol milk beverages, and other milk or-igin products.

(32) Nuts and nut products, includingwhole or shelled tree nuts, peanuts, co-conut, and nut and peanut spreads.

(33) Plant protein products, includingthe National Academy of Sciences/Na-tional Research Council ``reconstitutedvegetable protein'' category, and meat,poultry, and fish substitutes, analogs,and extender products made from plantproteins.

(34) Poultry products, including allpoultry and poultry-containing dishes,salads, appetizers, frozen multicoursepoultry meals, and sandwich ingredi-ents prepared by commercial proc-essing or using commercially processedpoultry with home preparation.

(35) Processed fruits and fruit juices,including all commercially processedfruits, citrus, berries, and mixtures;salads, juices and juice punches, con-centrates, dilutions, ``ades'', and drinksubstitutes made therefrom.

(36) Processed vegetables and vege-table juices, including all commer-cially processed vegetables, vegetabledishes, frozen multicourse vegetablemeals, and vegetable juices and blends.

(37) Snack foods, including chips,pretzels, and other novelty snacks.

(38) Soft candy, including candy bars,chocolates, fudge, mints, and otherchewy or nougat candies.

(39) Soups, home-prepared, includingmeat, fish, poultry, vegetable, andcombination home-prepared soups.

(40) Soups and soup mixes, includingcommercially prepared meat, fish,poultry, vegetable, and combinationsoups and soup mixes.

(41) Sugar, white, granulated, includ-ing only white granulated sugar.


821 CFR Ch. I (4100 Edition) 170.3

(42) Sugar substitutes, includinggranulated, liquid, and tablet sugarsubstitutes.

(43) Sweet sauces, toppings, and syr-ups, including chocolate, berry, fruit,corn syrup, and maple sweet sauces andtoppings.

(o) The following terms describe thephysical or technical functional effectsfor which direct human food ingredi-ents may be added to foods. They areadopted from the National Academy ofSciences/National Research Council na-tional survey of food industries, re-ported to the Food and Drug Adminis-tration under the contract title `ÀComprehensive Survey of Industry onthe Use of Food Chemicals GenerallyRecognized as Safe'' (September 1972),which is incorporated by reference.Copies are available from the NationalTechnical Information Service (NTIS),5285 Port Royal Rd., Springfield, VA22161, or available for inspection at theOffice of the Federal Register, 800North Capitol Street, NW., suite 700,Washington, DC 20408:

(1) `Ànticaking agents and free-flowagents'': Substances added to finelypowdered or crystalline food productsto prevent caking, lumping, or agglom-eration.

(2) `Àntimicrobial agents'': Sub-stances used to preserve food by pre-venting growth of microorganisms andsubsequent spoilage, including fungi-stats, mold and rope inhibitors, and theeffects listed by the National Academyof Sciences/National Research Councilunder ``preservatives.''

(3) `Àntioxidants'': Substances usedto preserve food by retarding deteriora-tion, rancidity, or discoloration due tooxidation.

(4) ``Colors and coloring adjuncts'':Substances used to impart, preserve, orenhance the color or shading of a food,including color stabilizers, color fixa-tives, color-retention agents, etc.

(5) ``Curing and pickling agents'':Substances imparting a unique flavorand/or color to a food, usually pro-ducing an increase in shelf life sta-bility.

(6) ``Dough strengtheners'': Sub-stances used to modify starch and glu-ten, thereby producing a more stabledough, including the applicable effectslisted by the National Academy of

Sciences/National Research Councilunder ``dough conditioner.''

(7) ``Drying agents'': Substances withmoisture-absorbing ability, used tomaintain an environment of low mois-ture.

(8) `Èmulsifiers and emulsifiersalts'': Substances which modify sur-face tension in the component phase ofan emulsion to establish a uniform dis-persion or emulsion.

(9) `Ènzymes'': Enzymes used to im-prove food processing and the qualityof the finished food.

(10) ``Firming agents'': Substancesadded to precipitate residual pectin,thus strengthening the supporting tis-sue and preventing its collapse duringprocessing.

(11) ``Flavor enhancers'': Substancesadded to supplement, enhance, or mod-ify the original taste and/or aroma of afood, without imparting a char-acteristic taste or aroma of its own.

(12) ``Flavoring agents and adju-vants'': Substances added to impart orhelp impart a taste or aroma in food.

(13) ``Flour treating agents'': Sub-stances added to milled flour, at themill, to improve its color and/or bakingqualities, including bleaching and ma-turing agents.

(14) ``Formulation aids'': Substancesused to promote or produce a desiredphysical state or texture in food, in-cluding carriers, binders, fillers, plasti-cizers, film-formers, and tableting aids,etc.

(15) ``Fumigants'': Volatile sub-stances used for controlling insects orpests.

(16) ``Humectants'': Hygroscopic sub-stances incorporated in food to pro-mote retention of moisture, includingmoisture-retention agents and anti-dusting agents.

(17) ``Leavening agents'': Substancesused to produce or stimulate produc-tion of carbon dioxide in baked goodsto impart a light texture, includingyeast, yeast foods, and calcium saltslisted by the National Academy ofSciences/National Research Councilunder ``dough conditioners.''

(18) ``Lubricants and release agents'':Substances added to food contact sur-faces to prevent ingredients and fin-ished products from sticking to them.


9Food and Drug Administration, HHS 170.6

(19) ``Non-nutritive sweeteners'': Sub-stances having less than 2 percent ofthe caloric value of sucrose per equiva-lent unit of sweetening capacity.

(20) ``Nutrient supplements'': Sub-stances which are necessary for thebody's nutritional and metabolic proc-esses.

(21) ``Nutritive sweeteners'': Sub-stances having greater than 2 percentof the caloric value of sucrose perequivalent unit of sweetening capacity.

(22) ``Oxidizing and reducing agents'':Substances which chemically oxidizeor reduce another food ingredient,thereby producing a more stable prod-uct, including the applicable effect list-ed by the National Academy ofSciences/National Research Councilunder ``dough conditioners.''

(23) ``pH control agents'': Substancesadded to change or maintain activeacidity or basicity, including buffers,acids, alkalies, and neutralizingagents.

(24) ``Processing aids'': Substancesused as manufacturing aids to enhancethe appeal or utility of a food or foodcomponent, including clarifyingagents, clouding agents, catalysts, floc-culents, filter aids, and crystallizationinhibitors, etc.

(25) ``Propellants, aerating agents,and gases'': Gases used to supply forceto expel a product or used to reduce theamount of oxygen in contact with thefood in packaging.

(26) ``Sequestrants'': Substanceswhich combine with polyvalent metalions to form a soluble metal complex,to improve the quality and stability ofproducts.

(27) ``Solvents and vehicles'': Sub-stances used to extract or dissolve an-other substance.

(28) ``Stabilizers and thickeners'':Substances used to produce viscous so-lutions or dispersions, to impart body,improve consistency, or stabilize emul-sions, including suspending and body-ing agents, setting agents, jellyingagents, and bulking agents, etc.

(29) ``Surface-active agents'': Sub-stances used to modify surface prop-erties of liquid food components for avariety of effects, other than emulsi-fiers, but including solubilizing agents,dispersants, detergents, wettingagents, rehydration enhancers, whip-

ping agents, foaming agents, and de-foaming agents, etc.

(30) ``Surface-finishing agents'': Sub-stances used to increase palatability,preserve gloss, and inhibit discolora-tion of foods, including glazes, polishes,waxes, and protective coatings.

(31) ``Synergists'': Substances used toact or react with another food ingre-dient to produce a total effect differentor greater than the sum of the effectsproduced by the individual ingredients.

(32) ``Texturizers'': Substances whichaffect the appearance or feel of thefood.

[42 FR 14483, Mar. 15, 1977, as amended at 47FR 11835, Mar. 19, 1982; 53 FR 16546, May 10,1988; 54 FR 24896, June 12, 1989; 60 FR 36595,July 17, 1995]

170.6 Opinion letters on food addi-tive status.

(a) Over the years the Food and DrugAdministration has given informalwritten opinions to inquiries as to thesafety of articles intended for use ascomponents of, or in contact with,food. Prior to the enactment of theFood Additives Amendment of 1958(Pub. L. 85929; Sept. 6, 1958), theseopinions were given pursuant to sec-tion 402(a)(1) of the Federal Food,Drug, and Cosmetic Act, which reads inpart: ``A food shall be deemed to beadulterated if it bears or contains anypoisonous or deleterious substancewhich may render it injurious tohealth''.

(b) Since enactment of the Food Ad-ditives Amendment, the Food and DrugAdministration has advised such in-quirers that an article:

(1) Is a food additive within themeaning of section 201(s) of the act; or

(2) Is generally recognized as safe(GRAS); or

(3) Has prior sanction or approvalunder that amendment; or

(4) Is not a food additive under theconditions of intended use.

(c) In the interest of the publichealth, such articles which have beenconsidered in the past by the Food andDrug Administration to be safe underthe provisions of section 402(a)(1), or tobe generally recognized as safe fortheir intended use, or to have priorsanction or approval, or not to be food


10

21 CFR Ch. I (4100 Edition) 170.10

additives under the conditions of in-tended use, must be reexamined in thelight of current scientific informationand current principles for evaluatingthe safety of food additives if their useis to be continued.

(d) Because of the time span in-volved, copies of many of the letters inwhich the Food and Drug Administra-tion has expressed an informal opinionconcerning the status of such articlesmay no longer be in the file of the Foodand Drug Administration. In the ab-sence of information concerning thenames and uses made of all the articlesreferred to in such letters, their safetyof use cannot be reexamined. For thisreason all food additive status opinionsof the kind described in paragraph (c)of this section given by the Food andDrug Administration are hereby re-voked.

(e) The prior opinions of the kind de-scribed in paragraph (c) of this sectionwill be replaced by qualified and cur-rent opinions if the recipient of eachsuch letter forwards a copy of each tothe Department of Health and HumanServices, Food and Drug Administra-tion, Center for Food Safety and Ap-plied Nutrition, 200 C Street SW.,Washington, DC 20204, along with acopy of his letter of inquiry, on or be-fore July 23, 1970.

(f) This section does not apply to foodadditive status opinion letters per-taining to articles that were consideredby the Food and Drug Administrationto be food additives nor to articles in-cluded in regulations in parts 170through 189 of this chapter if the arti-cles are used in accordance with the re-quirements of such regulations.

[42 FR 14483, Mar. 15, 1977, as amended at 54FR 24896, June 12, 1989]

170.10 Food additives in standard-ized foods.

(a) The inclusion of food ingredientsin parts 170 through 189 of this chapterdoes not imply that these ingredientsmay be used in standardized foods un-less they are recognized as optional in-gredients in applicable food standards.Where a petition is received for theissuance or amendment of a regulationestablishing a definition and standardof identity for a food under section 401of the Act, which proposes the inclu-

sion of a food additive in such defini-tion and standard of identity, the pro-visions of the regulations in this partshall apply with respect to the infor-mation that must be submitted withrespect to the food additive. Since sec-tion 409(b)(5) of the Act requires thatthe Secretary publish notice of a peti-tion for the establishment of a food-ad-ditive regulation within 30 days afterfiling, notice of a petition relating to adefinition and standard of identityshall also be published within thattime limitation if it includes a request,so designated, for the establishment ofa regulation pertaining to a food addi-tive.

(b) If a petition for a definition andstandard of identity contains a pro-posal for a food-additive regulation,and the petitioner fails to designate itas such, the Commissioner, upon deter-mining that the petition includes aproposal for a food-additive regulation,shall so notify the petitioner and shallthereafter proceed in accordance withthe regulations in this part.

(c) A regulation will not be issued al-lowing the use of a food additive in afood for which a definition and stand-ard of identity is established, unless itsissuance is in conformity with section401 of the Act or with the terms of atemporary permit issued under 130.17of this chapter. When the contemplateduse of such additive complies with theterms of a temporary permit, the foodadditive regulation will be conditionedon such compliance and will expirewith the expiration of the temporarypermit.

170.15 Adoption of regulation on ini-tiative of Commissioner.

(a) The Commissioner upon his owninitiative may propose the issuance ofa regulation prescribing, with respectto any particular use of a food additive,the conditions under which such addi-tive may be safely used. Notice of suchproposal shall be published in the FED-ERAL REGISTER and shall state the rea-sons for the proposal.

(b) Action upon a proposal made bythe Commissioner shall proceed as pro-vided in part 10 of this chapter.

[42 FR 14486, Mar. 15, 1977, as amended at 42FR 15673, Mar. 22, 1977]


11

Food and Drug Administration, HHS 170.19

170.17 Exemption for investigationaluse and procedure for obtaining au-thorization to market edible prod-ucts from experimental animals.

A food additive or food containing afood additive intended for investiga-tional use by qualified experts shall beexempt from the requirements of sec-tion 409 of the Act under the followingconditions:

(a) If intended for investigational usein vitro or in laboratory research ani-mals, it bears a label which statesprominently, in addition to the otherinformation required by the act, thewarning:

Caution. Contains a new food additive forinvestigational use only in laboratory re-search animals or for tests in vitro. Not foruse in humans.

(b) If intended for use in animalsother than laboratory research animalsand if the edible products of the ani-mals are to be marketed as food, per-mission for the marketing of the edibleproducts as food has been requested bythe sponsor, and authorization hasbeen granted by the Food and Drug Ad-ministration in accordance with 511.1of this chapter or by the Department ofAgriculture in accordance with 9 CFR309.17, and it bears a label which statesprominently, in addition to the otherinformation required by the Act, thewarning:

Caution. Contains a new food additive foruse only in investigational animals. Not foruse in humans.

Edible products of investigational animalsare not to be used for food unless authoriza-tion has been granted by the U.S. Food andDrug Administration or by the U.S. Depart-ment of Agriculture.

(c) If intended for nonclinical labora-tory studies in food-producing animals,the study is conducted in compliancewith the regulations set forth in part 58of this chapter.

[42 FR 14483, Mar. 15, 1977, as amended at 43FR 60021, Dec. 22, 1978]

170.18 Tolerances for related food ad-ditives.

(a) Food additives that cause similaror related pharmacological effects willbe regarded as a class, and in the ab-sence of evidence to the contrary, as

having additive toxic effects and willbe considered as related food additives.

(b) Tolerances established for suchrelated food additives may limit theamount of a common component thatmay be present, or may limit theamount of biological activity (such ascholinesterase inhibition) that may bepresent or may limit the total amountof related food additives that may bepresent.

(c) Where food additives from two ormore chemicals in the same class arepresent in or on a food, the tolerancefor the total of such additives shall bethe same as that for the additive hav-ing the lowest numerical tolerance inthis class, unless there are availablemethods that permit quantitative de-termination of the amount of each foodadditive present or unless it is shownthat a higher tolerance is reasonablyrequired for the combined additives toaccomplish the physical or technicaleffect for which such combined addi-tives are intended and that the highertolerance will be safe.

(d) Where residues from two or moreadditives in the same class are presentin or on a food and there are availablemethods that permit quantitative de-termination of each residue, the quan-tity of combined residues that arewithin the tolerance may be deter-mined as follows:

(1) Determine the quantity of eachresidue present.

(2) Divide the quantity of each res-idue by the tolerance that would applyif it occurred alone, and multiply by100 to determine the percentage of thepermitted amount of residue present.

(3) Add the percentages so obtainedfor all residues present.

(4) The sum of the percentage shallnot exceed 100 percent.

170.19 Pesticide chemicals in proc-essed foods.

When pesticide chemical residuesoccur in processed foods due to the useof raw agricultural commodities thatbore or contained a pesticide chemicalin conformity with an exemptiongranted or a tolerance prescribed undersection 408 of the Act, the processedfood will not be regarded as adulter-ated so long as good manufacturingpractice has been followed in removing


12

21 CFR Ch. I (4100 Edition) 170.20

any residue from the raw agriculturalcommodity in the processing (such asby peeling or washing) and so long asthe concentration of the residue in theprocessed food when ready to eat is notgreater than the tolerance prescribedfor the raw agricultural commodity.But when the concentration of residuein the processed food when ready to eatis higher than the tolerance prescribedfor the raw agricultural commodity,the processed food is adulterated unlessthe higher concentration is permittedby a tolerance obtained under section409 of the Act. For example, if fruitbearing a residue of 7 parts per millionof DDT permitted on the raw agricul-tural commodity is dried and a residuein excess of 7 parts per million of DDTresults on the dried fruit, the dehy-drated fruit is adulterated unless thehigher tolerance for DDT is authorizedby the regulations in this part. Foodthat is itself ready to eat, and whichcontains a higher residue than allowedfor the raw agricultural commodity,may not be legalized by blending ormixing with other foods to reduce theresidue in the mixed food below the tol-erance prescribed for the raw agricul-tural commodity.

Subpart BFood Additive Safety 170.20 General principles for evalu-

ating the safety of food additives.(a) In reaching a decision on any pe-

tition filed under section 409 of theAct, the Commissioner will give fullconsideration to the specific biologicalproperties of the compound and theadequacy of the methods employed todemonstrate safety for the proposeduse, and the Commissioner will beguided by the principles and proceduresfor establishing the safety of food addi-tives stated in current publications ofthe National Academy of Sciences-Na-tional Research Council. A petitionwill not be denied, however, by reasonof the petitioner's having followed pro-cedures other than those outlined inthe publications of the National Acad-emy of Sciences-National ResearchCouncil if, from available evidence, theCommissioner finds that the proce-dures used give results as reliable as,or more reliable than, those reasonablyto be expected from the use of the out-

lined procedures. In reaching a deci-sion, the Commissioner will give dueweight to the anticipated levels andpatterns of consumption of the additivespecified or reasonably inferrable. Forthe purposes of this section, the prin-ciples for evaluating safety of additivesset forth in the abovementioned publi-cations will apply to any substancethat may properly be classified as afood additive as defined in section201(s) of the Act.

(b) Upon written request describingthe proposed use of an additive and theproposed experiments to determine itssafety, the Commissioner will advise aperson who wishes to establish thesafety of a food additive whether he be-lieves the experiments planned willyield data adequate for an evaluationof the safety of the additive.

170.22 Safety factors to be consid-ered.

In accordance with section409(c)(5)(C) of the Act, the followingsafety factors will be applied in deter-mining whether the proposed use of afood additive will be safe: Except whereevidence is submitted which justifiesuse of a different safety factor, a safetyfactor in applying animal experimen-tation data to man of 100 to 1, will beused; that is, a food additive for use byman will not be granted a tolerancethat will exceed 1100th of the maximumamount demonstrated to be withoutharm to experimental animals.

170.30 Eligibility for classification asgenerally recognized as safe(GRAS).

(a) General recognition of safety maybe based only on the views of expertsqualified by scientific training and ex-perience to evaluate the safety of sub-stances directly or indirectly added tofood. The basis of such views may be ei-ther (1) scientific procedures or (2) inthe case of a substance used in foodprior to January 1, 1958, through expe-rience based on common use in food.General recognition of safety requirescommon knowledge about the sub-stance throughout the scientific com-munity knowledgeable about the safetyof substances directly or indirectlyadded to food.


13


(b) General recognition of safetybased upon scientific procedures shallrequire the same quantity and qualityof scientific evidence as is required toobtain approval of a food additive regu-lation for the ingredient. General rec-ognition of safety through scientificprocedures shall ordinarily be basedupon published studies which may becorroborated by unpublished studiesand other data and information.

(c)(1) General recognition of safetythrough experience based on commonuse in food prior to January 1, 1958,may be determined without the quan-tity or quality of scientific proceduresrequired for approval of a food additiveregulation. General recognition of safe-ty through experience based on com-mon use in food prior to January 1,1958, shall be based solely on food useof the substance prior to January 1,1958, and shall ordinarily be based upongenerally available data and informa-tion. An ingredient not in common usein food prior to January 1, 1958, mayachieve general recognition of safetyonly through scientific procedures.

(2) A substance used in food prior toJanuary 1, 1958, may be generally rec-ognized as safe through experiencebased on its common use in food whenthat use occurred exclusively or pri-marily outside of the United States ifthe information about the experienceestablishes that the use of the sub-stance is safe within the meaning ofthe act (see 170.3(i)). Common use infood prior to January 1, 1958, that oc-curred outside of the United Statesshall be documented by published orother information and shall be corrobo-rated by information from a second,independent source that confirms thehistory and circumstances of use of thesubstance. The information used todocument and to corroborate the his-tory and circumstances of use of thesubstance must be generally available;that is, it must be widely available inthe country in which the history of usehas occurred and readily available tointerested qualified experts in thiscountry. Persons claiming GRAS sta-tus for a substance based on its com-mon use in food outside of the UnitedStates should obtain FDA concurrencethat the use of the substance is GRAS.

(d) The food ingredients listed asGRAS in part 182 of this chapter or af-firmed as GRAS in part 184 or 186.1 ofthis chapter do not include all sub-stances that are generally recognizedas safe for their intended use in food.Because of the large number of sub-stances the intended use of which re-sults or may reasonably be expected toresult, directly or indirectly, in theirbecoming a component or otherwise af-fecting the characteristics of food, it isimpracticable to list all such sub-stances that are GRAS. A food ingre-dient of natural biological origin thathas been widely consumed for its nutri-ent properties in the United Statesprior to January 1, 1958, without knowndetrimental effects, which is subjectonly to conventional processing aspracticed prior to January 1, 1958, andfor which no known safety hazard ex-ists, will ordinarily be regarded asGRAS without specific inclusion inpart 182, part 184 or 186.1 of this chap-ter.

(e) Food ingredients were listed asGRAS in part 182 of this chapter during19581962 without a detailed scientificreview of all available data and infor-mation relating to their safety. Begin-ning in 1969, the Food and Drug Admin-istration has undertaken a systematicreview of the status of all ingredientsused in food on the determination thatthey are GRAS or subject to a priorsanction. All determinations of GRASstatus or food additive status or priorsanction status pursuant to this reviewshall be handled pursuant to 170.35,170.38, and 180.1 of this chapter. Affir-mation of GRAS status shall be an-nounced in part 184 or 186.1 of thischapter.

(f) The status of the following foodingredients will be reviewed and af-firmed as GRAS or determined to be afood additive or subject to a prior sanc-tion pursuant to 170.35, 170.38, or 180.1 of this chapter:

(1) Any substance of natural biologi-cal origin that has been widely con-sumed for its nutrient properties in theUnited States prior to January 1, 1958,without known detrimental effect, forwhich no health hazard is known, andwhich has been modified by processesfirst introduced into commercial use


14

21 CFR Ch. I (4100 Edition) 170.30

after January 1, 1958, which may rea-sonably be expected significantly toalter the composition of the substance.

(2) Any substance of natural biologi-cal origin that has been widely con-sumed for its nutrient properties in theUnited States prior to January 1, 1958,without known detrimental effect, forwhich no health hazard is known, thathas had significant alteration of com-position by breeding or selection afterJanuary 1, 1958, where the change maybe reasonably expected to alter the nu-tritive value or the concentration oftoxic constituents.

(3) Distillates, isolates, extracts, andconcentration of extracts of GRAS sub-stances.

(4) Reaction products of GRAS sub-stances.

(5) Substances not of a natural bio-logical origin, including those forwhich evidence is offered that they areidentical to a GRAS counterpart ofnatural biological origin.

(6) Substances of natural biologicalorigin intended for consumption forother than their nutrient properties.

(g) A food ingredient that is notGRAS or subject to a prior sanction re-quires a food additive regulation pro-mulgated under section 409 of the actbefore it may be directly or indirectlyadded to food.

(h) A food ingredient that is listed asGRAS in part 182 of this chapter or af-firmed as GRAS in part 184 or 186.1 ofthis chapter shall be regarded as GRASonly if, in addition to all the require-ments in the applicable regulation, italso meets all of the following require-ments:

(1) It complies with any applicablefood grade specifications of the FoodChemicals Codex, 2d Ed. (1972), or, ifspecifically indicated in the GRAS af-firmation regulation, the Food Chemi-cals Codex, 3d Ed. (1981), which are in-corporated by reference, except thatany substance used as a component ofarticles that contact food and affirmedas GRAS in 186.1 of this chapter shallcomply with the specifications therein,or in the absence of such specifications,shall be of a purity suitable for its in-tended use. Copies may be obtainedfrom the National Academy Press, 2101Constitution Ave. NW., Washington,DC 20418, or may be examined at the

Office of the Federal Register, 800North Capitol Street, NW., suite 700,Washington, DC 20408.

(2) It performs an appropriate func-tion in the food or food-contact articlein which it is used.

(3) It is used at a level no higher thannecessary to achieve its intended pur-pose in that food or, if used as a compo-nent of a food-contact article, at alevel no higher than necessary toachieve its intended purpose in that ar-ticle.

(i) If a substance is affirmed as GRASin part 184 or 186.1 of this chapter withno limitation other than good manu-facturing practice, it shall be regardedas GRAS if its conditions of use are notsignificantly different from those re-ported in the regulation as the basis onwhich the GRAS status of the sub-stance was affirmed. If the conditionsof use are significantly different, suchuse of the substance may not be GRAS.In such a case a manufacturer may notrely on the regulation as authorizingthe use but must independently estab-lish that the use is GRAS or must usethe substance in accordance with afood additive regulation.

(j) If an ingredient is affirmed asGRAS in part 184 or 186.1 of this chap-ter with specific limitation(s), it maybe used in food only within such limi-tation(s) (including the category offood(s), the functional use(s) of the in-gredient, and the level(s) of use). Anyuse of such an ingredient not in fullcompliance with each such establishedlimitation shall require a food additiveregulation.

(k) Pursuant to 170.35, a food ingre-dient may be affirmed as GRAS in part184 or 186.1 of this chapter for a spe-cific use(s) without a general evalua-tion of use of the ingredient. In addi-tion to the use(s) specified in the regu-lation, other uses of such an ingredientmay also be GRAS. Any affirmation ofGRAS status for a specific use(s), with-out a general evaluation of use of theingredient, is subject to reconsider-ation upon such evaluation.

(l) New information may at any timerequire reconsideration of the GRASstatus of a food ingredient. Any changein part 182, part 184, or 186.1 of this


15


chapter shall be accomplished pursuantto 170.38.

[42 FR 14483, Mar. 15, 1977, as amended at 49FR 5610, Feb. 14, 1984; 53 FR 16546, May 10,1988]

170.35 Affirmation of generally recog-nized as safe (GRAS) status.

(a) The Commissioner, either on hisinitiative or on the petition of an in-terested person, may affirm the GRASstatus of substances that directly orindirectly become components of food.

(b)(1) If the Commissioner proposeson his own initiative that a substanceis entitled to affirmation as GRAS, hewill place all of the data and informa-tion on which he relies on public file inthe office of the Dockets ManagementBranch and will publish in the FEDERALREGISTER a notice giving the name ofthe substance, its proposed uses, andany limitations proposed for purposesother than safety.

(2) The FEDERAL REGISTER notice willallow a period of 60 days during whichany interested person may review thedata and information and/or file com-ments with the Dockets ManagementBranch. Copies of all comments re-ceived shall be made available for ex-amination in the Dockets ManagementBranch's office.

(3) The Commissioner will evaluateall comments received. If he concludesthat there is convincing evidence thatthe substance is GRAS as described in 170.30, he will publish a notice in theFEDERAL REGISTER listing the sub-stance as GRAS in part 182, part 184, orpart 186 of this chapter, as appropriate.

(4) If, after evaluation of the com-ments, the Commissioner concludesthat there is a lack of convincing evi-dence that the substance is GRAS andthat it should be considered a food ad-ditive subject to section 409 of the Act,he shall publish a notice thereof in theFEDERAL REGISTER in accordance with 170.38.

(c)(1) Persons seeking the affirmationof GRAS status of substances as pro-vided in 170.30(e), except those subjectto the NAS/NRC GRAS list survey (36FR 20546; October 23, 1971), shall submita petition for GRAS affirmation pursu-ant to part 10 of this chapter. Such pe-tition shall contain information to es-tablish that the GRAS criteria as set

forth in 170.30 (b) or (c) have been met,in the following form:

(i) Description of the substance, in-cluding:

(a) Common or usual name.(b) Chemical name.(c) Chemical Abstract Service (CAS)

registry number.(d) Empirical formula.(e) Structural formula.(f) Specifications for food grade ma-

terial, including arsenic and heavymetals. (Recommendation for anychange in the Food Chemicals Codexmonograph should be included whereapplicable.)

(g) Quantitative compositions.(h) Manufacturing process (excluding

any trade secrets).(ii) Use of the substance, including:(a) Date when use began.(b) Information and reports or other

data on past uses in food.(c) Foods in which used, and levels of

use in such foods, and for what pur-poses.

(iii) Methods for detecting the sub-stance in food, including:

(a) References to qualitative andquantitative methods for determiningthe substance(s) in food, including thetype of analytical procedures used.

(b) Sensitivity and reproducibility ofsuch method(s).

(iv) Information to establish the safe-ty and functionality of the substancein food. Published scientific literature,evidence that the substance is identicalto a GRAS counterpart of natural bio-logical origin, and other data may besubmitted to support safety. Any ad-verse information or consumer com-plaints shall be included. Complete bib-liographic references shall be providedwhere a copy of the article is not pro-vided.

(v) A statement signed by the personresponsible for the petition that to thebest of his knowledge it is a represent-ative and balanced submission that in-cludes unfavorable information, as wellas favorable information, known tohim pertinent to the evaluation of thesafety and functionality of the sub-stance.

(vi) If nonclinical laboratory studiesare involved, additional informationand data submitted in support of filedpetitions shall include, with respect to


16

21 CFR Ch. I (4100 Edition) 170.38

each nonclinical study, either a state-ment that the study was conducted incompliance with the requirements setforth in part 58 of this chapter, or, ifthe study was not conducted in compli-ance with such regulations, a briefstatement of the reason for the non-compliance.

(vii) [Reserved](viii) A claim for categorical exclu-

sion under 25.30 or 25.32 of this chap-ter or an environmental assessmentunder 25.40 of this chapter.

(2) Within 30 days after the date offiling the petition, the Commissionerwill place the petition on public file inthe office of the Dockets ManagementBranch and will publish a notice of fil-ing in the FEDERAL REGISTER givingthe name of the petitioner and a briefdescription of the petition includingthe name of the substance, its proposeduse, and any limitations proposed forreasons other than safety. A copy ofthe notice will be mailed to the peti-tioner at the time the original is sentto the FEDERAL REGISTER.

(3) The notice of filing in the FED-ERAL REGISTER will allow a period of 60days during which any interested per-son may review the petition and/or filecomments with the Dockets Manage-ment Branch. Copies of all commentsreceived shall be made available for ex-amination in the Dockets ManagementBranch's office.

(4) The Commissioner will evaluatethe petition and all available informa-tion including all comments received.If the petition and such informationprovide convincing evidence that thesubstance is GRAS as described in 170.30 he will publish an order in theFEDERAL REGISTER listing the sub-stance as GRAS in part 182, part 184, orpart 186 of this chapter, as appropriate.

(5) If, after evaluation of the petitionand all available information, the Com-missioner concludes that there is alack of convincing evidence that thesubstance is GRAS and that it shouldbe considered a food additive subject tosection 409 of the Act, he shall publisha notice thereof in the FEDERAL REG-ISTER in accordance with 170.38.

(6) The notice of filing in the FED-ERAL REGISTER will request submissionof proof of any applicable prior sanc-tion for use of the ingredient under

conditions different from those pro-posed to be determined to be GRAS.The failure of any person to come for-ward with proof of such an applicableprior sanction in response to the noticeof filing will constitute a waiver of theright to assert or rely on such sanctionat any later time. The notice of filingwill also constitute a proposal to estab-lish a regulation under part 181 of thischapter, incorporating the same provi-sions, in the event that such a regula-tion is determined to be appropriate asa result of submission of proof of suchan applicable prior sanction in re-sponse to the notice of filing.

(Information collection requirements wereapproved by the Office of Management andBudget under control number 09100132)

[42 FR 14488, Mar. 15, 1977, as amended at 50FR 7492, Feb. 22, 1985; 50 FR 16668, Apr. 26,1985; 53 FR 16547, May 10, 1988; 62 FR 40599,July 29, 1997]

170.38 Determination of food addi-tive status.

(a) The Commissioner may, in ac-cordance with 170.35(b)(4) or (c)(5),publish a notice in the FEDERAL REG-ISTER determining that a substance isnot GRAS and is a food additive sub-ject to section 409 of the Act.

(b)(1) The Commissioner, on his owninitiative or on the petition of any in-terested person, pursuant to part 10 ofthis chapter, may issue a notice in theFEDERAL REGISTER proposing to deter-mine that a substance is not GRAS andis a food additive subject to section 409of the Act. Any petition shall includeall relevant data and information ofthe type described in 171.130(b). TheCommissioner will place all of the dataand information on which he relies onpublic file in the office of the DocketsManagement Branch and will includein the FEDERAL REGISTER notice thename of the substance, its known uses,and a summary of the basis for the de-termination.

(2) The FEDERAL REGISTER notice willallow a period of 60 days during whichany interested person may review thedata and information and/or file com-ments with the Dockets ManagementBranch. Copies of all comments shallbe made available for examination inthe Dockets Management Branch's of-fice.


17


(3) The Commissioner will evaluateall comments received. If he concludesthat there is a lack of convincing evi-dence that the substance is GRAS or isotherwise exempt from the definitionof a food additive in section 201(s) ofthe Act, he will publish a notice there-of in the FEDERAL REGISTER. If he con-cludes that there is convincing evi-dence that the substance is GRAS, hewill publish an order in the FEDERALREGISTER listing the substance asGRAS in part 182, part 184, or part 186of this chapter, as appropriate.

(c) A FEDERAL REGISTER notice deter-mining that a substance is a food addi-tive shall provide for the use of the ad-ditive in food or food contact surfacesas follows:

(1) It may promulgate a food additiveregulation governing use of the addi-tive.

(2) It may promulgate an interimfood additive regulation governing useof the additive.

(3) It may require discontinuation ofthe use of the additive.

(4) It may adopt any combination ofthe above three approaches for dif-ferent uses or levels of use of the addi-tive.

(d) If the Commissioner of Food andDrugs is aware of any prior sanctionfor use of the substance, he will con-currently propose a separate regulationcovering such use of the ingredientunder part 181 of this chapter. If theCommissioner is unaware of any suchapplicable prior sanction, the proposedregulation will so state and will re-quire any person who intends to assertor rely on such sanction to submitproof of its existence. Any regulationpromulgated pursuant to this sectionconstitutes a determination that ex-cluded uses would result in adultera-tion of the food in violation of section402 of the Act, and the failure of anyperson to come forward with proof ofsuch an applicable prior sanction in re-sponse to the proposal will constitute awaiver of the right to assert or rely onsuch sanction at any later time. Thenotice will also constitute a proposalto establish a regulation under part 181of this chapter, incorporating the sameprovisions, in the event that such aregulation is determined to be appro-priate as a result of submission of proof

of such an applicable prior sanction inresponse to the proposal.

[42 FR 14488, Mar. 15, 1977, as amended at 42FR 15673, Mar. 22, 1977; 54 FR 24896, June 12,1989]

170.39 Threshold of regulation forsubstances used in food-contact ar-ticles.

(a) A substance used in a food-con-tact article (e.g., food-packaging orfood-processing equipment) that mi-grates, or that may be expected to mi-grate, into food will be exempted fromregulation as a food additive because itbecomes a component of food at levelsthat are below the threshold of regula-tion if:

(1) The substance has not been shownto be a carcinogen in humans or ani-mals, and there is no reason, based onthe chemical structure of the sub-stance, to suspect that the substance isa carcinogen. The substance must alsonot contain a carcinogenic impurity or,if it does, must not contain a carcino-genic impurity with a TD50 value basedon chronic feeding studies reported inthe scientific literature or otherwiseavailable to the Food and Drug Admin-istration of less than 6.25 milligramsper kilogram bodyweight per day (TheTD50, for the purposes of this section, isthe feeding dose that causes cancer in50 percent of the test animals whencorrected for tumors found in controlanimals. If more than one TD50 valuehas been reported in the scientific lit-erature for a substance, the Food andDrug Administration will use the low-est appropriate TD50 value in its re-view.);

(2) The substance presents no otherhealth or safety concerns because:

(i) The use in question has beenshown to result in or may be expectedto result in dietary concentrations ator below 0.5 parts per billion, cor-responding to dietary exposure levelsat or below 1.5 micrograms/person/day(based on a diet of 1,500 grams of solidfood and 1,500 grams of liquid food perperson per day); or

(ii) The substance is currently regu-lated for direct addition into food, andthe dietary exposure to the substanceresulting from the proposed use is at orbelow 1 percent of the acceptable dailyintake as determined by safety data in


18

21 CFR Ch. I (4100 Edition) 170.39

the Food and Drug Administration'sfiles or from other appropriate sources;

(3) The substance has no technical ef-fect in or on the food to which it mi-grates; and

(4) The substance use has no signifi-cant adverse impact on the environ-ment.

(b) Notwithstanding paragraph (a) ofthis section, the Food and Drug Admin-istration reserves the right to declineto grant an exemption in those cases inwhich available information estab-lishes that the proposed use may pose apublic health risk. The reasons for theagency's decision to decline to grant anexemption will be explained in theFood and Drug Administration's re-sponse to the requestor.

(c) A request for the Food and DrugAdministration to exempt a use of asubstance from regulation as a food ad-ditive shall include three copies of thefollowing information (If part of thesubmitted material is in a foreign lan-guage, it must be accompanied by anEnglish translation verified to be com-plete and accurate in accordance with 10.20(c)(2) of this chapter):

(1) The chemical composition of thesubstance for which the request ismade, including, whenever possible,the name of the chemical in accord-ance with current Chemical AbstractService (CAS) nomenclature guidelinesand a CAS registry number, if avail-able;

(2) Detailed information on the con-ditions of use of the substance (e.g.,temperature, type of food with whichthe substance will come into contact,the duration of the contact, and wheth-er the food-contact article will be forrepeated or single use applications);

(3) A clear statement as to whetherthe request for exemption from regula-tion as a food additive is based on thefact that the use of the substance inthe food-contact article results in a di-etary concentration at or below 0.5parts per billion, or on the fact that itinvolves the use of a regulated directfood additive for which the dietary ex-posure is at or below 1 percent of theacceptable dietary intake (ADI);

(4) Data that will enable the Foodand Drug Administration to estimatethe daily dietary concentration result-ing from the proposed use of the sub-

stance. These data should be in theform of:

(i) Validated migration data obtainedunder worst-case (time/temperature)intended use conditions utilizing ap-propriate food simulating solvents;

(ii) Information on the amount of thesubstance used in the manufacture ofthe food-contact article; or

(iii) Information on the residual levelof the substance in the food-contact ar-ticle. For repeat-use articles, an esti-mate of the amount of food that con-tacts a specific unit of surface areaover the lifetime of the article shouldalso be provided. (In cases where dataare provided only in the form of manu-facturing use levels or residual levelsof the substance present in the food-contact article, the Food and Drug Ad-ministration will calculate a worst-case dietary concentration level as-suming 100 percent migration.) A de-tailed description of the analyticalmethod used to quantify the substanceshould also be submitted along withdata used to validate the detectionlimit.

(iv) In cases where there is no detect-able migration into food or foodsimulants, or when no residual level ofa substance is detected in the food-con-tact article by a suitable analyticalmethod, the Food and Drug Adminis-tration will, for the purposes of esti-mating the dietary concentration, con-sider the validated detection limit ofthe method used to analyze for the sub-stance.

(5) The results of an analysis of exist-ing toxicological information on thesubstance and its impurities. This in-formation on the substance is neededto show whether an animal carcinogenbioassay has been carried out, orwhether there is some other basis forsuspecting that the substance is a car-cinogen or potent toxin. This type ofinformation on the impurities is need-ed to show whether any of them arecarcinogenic, and, if carcinogenic,whether their TD50 values are greaterthan 6.25 milligrams per kilogrambodyweight per day in accordance withparagraph (a)(1) of this section.

(6) Information on the environmentalimpact that would result from the pro-posed use of the substance. The request


19


should contain either a claim for cat-egorical exclusion as specified in 25.32of this chapter or an environmental as-sessment as specified in 25.40 of thischapter.

(d) Data to be reviewed under thissection shall be submitted to the Foodand Drug Administration's Office ofPremarket Approval (HFS200), 200 CSt. SW., Washington, DC 20204.

(e) The Food and Drug Administra-tion will inform the requestor by letterwhether the specific food-contact ap-plication is exempt from regulation asa food additive or not. Although a sub-stance that migrates to food at a levelthat results in a dietary concentrationat or below the threshold of regulationwill not be the subject of a regulationpublished in the FEDERAL REGISTERand will not appear in the Code of Fed-eral Regulations, the Food and DrugAdministration will maintain a list ofsubstances exempted from regulationas food additives under this section ondisplay at the Dockets ManagementBranch. This list will include the nameof the company that made the request,the chemical name of the substance,the specific use for which it has re-ceived an exemption from regulation asa food additive, and any appropriatelimitations on its use. The list will notinclude any trade names. This list willenable interested persons to see thetypes of uses of food-contact materialsbeing exempted under the regulation.Interested persons may also obtain acopy of the list of exempted substancesby contacting the Food and Drug Ad-ministration's Office of Premarket Ap-proval (HFS200), 200 C St. SW., Wash-ington, DC 20204. For actions requiringan environmental assessment, theagency's finding of no significant im-pact and the evidence supporting thatfinding, contained in the petitioner'senvironmental assessment, also will beavailable for public inspection at theDockets Management Branch in ac-cordance with 25.51(b)(2) of this chap-ter. Requests for copies of releasableinformation contained in submissionsrequesting exemptions from the foodadditive regulations will be handled inaccordance with the Food and Drug Ad-ministration's Freedom of InformationAct procedures, as described in part 20of this chapter. In particular, data and

information that fall within the defini-tions of a trade secret or confidentialcommercial or financial informationare not available for public disclosurein accordance with 20.61(c) of thischapter.

(f) If the request for an exemptionfrom regulation as a food additive isnot granted, the requestor may submita petition to the Food and Drug Ad-ministration for reconsideration of thedecision in accordance with the provi-sions of 10.33 of this chapter.

(g) If the Food and Drug Administra-tion receives significant new informa-tion that raises questions about the di-etary concentration or the safety of asubstance that the agency has exempt-ed from regulation, the Food and DrugAdministration may reevaluate thesubstance. If the Food and Drug Ad-ministration tentatively concludesthat the information that is availableabout the substance no longer supportsan exemption for the use of the food-contact material from the food addi-tive regulations, the agency will notifyany persons that requested an exemp-tion for the substance of its tentativedecision. The requestors will be givenan opportunity to show why the use ofthe substance should not be regulatedunder the food additive provisions ofthe act. If the requestors fail to ade-quately respond to the new evidence,the agency will notify them that fur-ther use of the substance in questionfor the particular use will require afood additive regulation. This notifica-tion will be placed on public display atthe Dockets Management Branch aspart of the file of uses of substances ex-empted from regulation as food addi-tives. The Food and Drug Administra-tion recognizes that manufacturersother than those that actually made arequest for exemption may also beusing exempted substances in food-con-tact articles under conditions of use(e.g., use levels, temperature, type offood contacted, etc.) that are similar tothose for which the exemption wasissued. Because only requestors will benotified as part of the revocation proc-ess described in this section, the Foodand Drug Administration plans to no-tify other manufacturers by means of a


20

21 CFR Ch. I (4100 Edition) 170.45

notice published in the FEDERAL REG-ISTER of its decision to revoke an ex-emption issued for a specific use of asubstance in a food contact article.

(h) Guidelines to assist requestors inthe preparation of submissions seekingexemptions from the food additive reg-ulations are available from the Foodand Drug Administration's Office ofPremarket Approval (HFS200), 200 CSt. SW., Washington, DC 20204. Inter-ested persons are encouraged to obtainspecific guidance from the Food andDrug Administration on the appro-priate protocols to be used for obtain-ing migration data, on the validationof the analytical methods used toquantify migration levels, on the pro-cedures used to relate migration datato dietary exposures, and on any otherissue not specifically covered in theFood and Drug Administration's guide-lines.

[60 FR 36595, July 17, 1995, as amended at 62FR 40599, July 29, 1997]

Subpart CSpecific Administra-tive Rulings and Decisions

170.45 Fluorine-containing com-pounds.

The Commissioner of Food and Drugshas concluded that it is in the interestof the public health to limit the addi-tion of fluorine compounds to foods (a)to that resulting from the fluoridationof public water supplies as stated in 250.203 of this chapter, (b) to that re-sulting from the fluoridation of bottledwater within the limitation establishedin 103.35(d) of this chapter, and (c) tothat authorized by regulations (40 CFRpart 180) under section 408 of the Act.

170.50 Glycine (aminoacetic acid) infood for human consumption.

(a) Heretofore, the Food and DrugAdministration has expressed the opin-ion in trade correspondence that gly-cine is generally recognized as safe forcertain technical effects in human foodwhen used in accordance with goodmanufacturing practice; however:

(1) Reports in scientific literature in-dicate that adverse effects were foundin cases where high levels of glycinewere administered in diets of experi-mental animals.

(2) Current usage information indi-cates that the daily dietary intake ofglycine by humans may be substan-tially increasing due to changing usepatterns in food technology.Therefore, the Food and Drug Adminis-tration no longer regards glycine andits salts as generally recognized as safefor use in human food and all out-standing letters expressing sanction forsuch use are rescinded.

(b) The Commissioner of Food andDrugs concludes that by May 8, 1971,manufacturers:

(1) Shall reformulate food productsfor human use to eliminate added gly-cine and its salts; or

(2) Shall bring such products intocompliance with an authorizing foodadditive regulation. A food additive pe-tition supported by toxicity data is re-quired to show that any proposed levelof glycine or its salts added to foods forhuman consumption will be safe.

(c) The status of glycine as generallyrecognized as safe for use in animalfeed, as prescribed in 582.5049 of thischapter, remains unchanged becausethe additive is considered an essentialnutrient in certain animal feeds and issafe for such use under conditions ofgood feeding practice.

170.60 Nitrites and/or nitrates in cur-ing premixes.

(a) Nitrites and/or nitrates are foodadditives when combined in curing pre-mixes with spices and/or other fla-voring or seasoning ingredients thatcontain or constitute a source of sec-ondary or tertiary amines, includingbut not limited to essential oils, diso-dium inosinate, disodium guanylate,hydrolysates of animal or plant origin(such as hydrolyzed vegetable protein),oleoresins of spices, soy products, andspice extractives. Such food additivesmay be used only after the establish-ment of an authorizing food additiveregulation. A food additive petitionsubmitted pursuant to 171.1 and171.100 of this chapter, supported bydata demonstrating that nitrosaminesare not formed in curing premixes con-taining such food additives, is requiredto establish safety.

(b) Nitrites and/or nitrates, whenpackaged separately from flavoringand seasoning in curing premixes, may


21


continue to be used under prior sanc-tions in the commercial curing of meatand meat products and poultry prod-ucts and in accordance with the provi-sions of 172.170 and 172.175 of thischapter that apply to meat curingpreparations for the home curing ofmeat and meat products, includingpoultry and wild game. To assure safeuse of such ingredients the labeling ofthe premixes shall bear instructions tothe user that such separately packagedingredients are not to be combineduntil just prior to use. Encapsulatingor coating some or all of the ingredi-ents does not constitute separate pack-aging.

PART 171FOOD ADDITIVEPETITIONS


Sec.171.1 Petitions.171.6 Amendment of petition.171.7 Withdrawal of petition without preju-

dice.171.8 Threshold of regulation for substances

used in foodcontact articles.

Subpart BAdministrative Actions onApplications

171.100 Regulation based on petition.171.102 Effective date of regulation.171.110 Procedure for objections and hear-

ings.171.130 Procedure for amending and repeal-

ing tolerances or exemptions from toler-ances.

AUTHORITY: 21 U.S.C. 321, 342, 348, 371.

SOURCE: 42 FR 14489, Mar. 15, 1977, unlessotherwise noted.


171.1 Petitions.(a) Petitions to be filed with the

Commissioner under the provisions ofsection 409(b) of the Act shall be sub-mitted in triplicate. If any part of thematerial submitted is in a foreign lan-guage, it shall be accompanied by anaccurate and complete English trans-lation. The petition shall state peti-tioner's post office address to whichpublished notices or orders issued orobjections filed pursuant to section 409of the Act may be sent.

(b) Pertinent information may be in-corporated in, and will be considered aspart of, a petition on the basis of spe-cific reference to such information sub-mitted to and retained in the files ofthe Food and Drug Administration.However, any reference to unpublishedinformation furnished by a personother than the applicant will not beconsidered unless use of such informa-tion is authorized in a written state-ment signed by the person who sub-mitted it. Any reference to publishedinformation offered in support of a foodadditive petition should be accom-panied by reprints or photostatic cop-ies of such references.

(c) Petitions shall include the fol-lowing data and be submitted in thefollowing form:

(Date)Name of petitioner lllllllllllllPost-office address lllllllllllllDate lllllllllllllllllllllName of food additive and proposed use llllllllllllllllllllllllll

Petitions Control BranchFood and Drug AdministrationDepartment of Health and Human ServicesWashington, DC 20204.

DEAR SIRS:The undersigned, lllll submits this

petition pursuant to section 409(b)(1) of theFederal Food, Drug, and Cosmetic Act withrespect to lllll

(Name of the food additive and proposed use)

Attached hereto, in triplicate, and consti-tuting a part of this petition, are the fol-lowing:

A. The name and all pertinent informationconcerning the food additive, includingchemical identity and composition of thefood additive, its physical, chemical, and bi-ological properties, and specifications pre-scribing the minimum content of the desiredcomponent(s) and identifying and limitingthe reaction byproducts and other impuri-ties. Where such information is not avail-able, a statement as to the reasons why it isnot should be submitted.

When the chemical identity and composi-tion of the food additive is not known, thepetition shall contain information in suffi-cient detail to permit evaluation regardingthe method of manufacture and the analyt-ical controls used during the various stagesof manufacturing, processing, or packing ofthe food additive which are relied upon to es-tablish that it is a substance of reproduciblecomposition. Alternative methods and con-trols and variations in methods and controlswithin reasonable limits that do not affect


22

21 CFR Ch. I (4100 Edition) 171.1

the characteristics of the substance or thereliability of the controls may be specified.

If the food additive is a mi