21 C.F.R. PART 570—FOOD ADDITIVES
Title 21 - Food and Drugs
Authority: 21 U.S.C. 321, 341, 342, 346a, 348, 371.
Source: 41 FR 38644, Sept. 10, 1976, unless otherwise noted.
(a) Secretary means the Secretary of Health and Human Services. (b) Department means the Department of Health and Human Services. (c) Commissioner means the Commissioner of Food and Drugs. (d) As used in this part, the term act means the Federal Food, Drug, and Cosmetic Act approved June 25, 1936 (52 Stat. 1040 et seq., as amended; 21 U.S.C. 301–392). (e) Food additives includes all substances not exempted by section 201(s) of the act, the intended use of which results or may reasonably be expected to result, directly or indirectly, either in their becoming a component of food or otherwise affecting the characteristics of food. A material used in the production of containers and packages is subject to the definition if it may reasonably be expected to become a component, or to affect the characteristics, directly or indirectly, of food packed in the container. Affecting the characteristics of food does not include such physical effects, as protecting contents of packages, preserving shape, and preventing moisture loss. If there is no migration of a packaging component from the package to the food, it does not become a component of the food and thus is not a food additive. A substance that does not become a component of food, but that is used, for example, in preparing an ingredient of the food to give a different flavor, texture, or other characteristic in the food, may be a food additive. (f) Common use in food means a substantial history of consumption of a substance by a significant number of animals in the United States. (g) The word substance in the definition of the term food additive includes a food or feed or a component of a food or feed consisting of one or more ingredients. (h) Scientific procedures include those human, animal, analytical, and other scientific studies, whether published or unpublished, appropriate to establish the safety of a substance. (i) Safe or safety means that there is a reasonable certainty in the minds of competent scientists that the substance is not harmful under the intended conditions of use. It is impossible in the present state of scientific knowledge to establish with complete certainty the absolute harmlessness of the use of any substance. Safety may be determined by scientific procedures or by general recognition of safety. In determining safety, the following factors shall be considered: (1) The probable consumption of the substance and of any substance formed in or on food because of its use; (2) The cumulative effect of the substance in the diet, taking into account any chemically or pharmacologically related substance or substances in such diet; (3) Safety factors which, in the opinion of experts qualified by scientific training and experience to evaluate the safety of food and food ingredients, are generally recognized as appropriate. (j) The term nonperishable processed food means any processed food not subject to rapid decay or deterioration that would render it unfit for consumption. Not included are hermetically sealed foods and other processed foods requiring refrigeration. (k) General recognition of safety shall be determined in accordance with §570.30. (l) Prior sanction means an explicit approval granted with respect to use of a substance in food prior to September 6, 1958, by the Food Drug and Administration or the United States Department of Agriculture pursuant to the Federal Food, Drug, and Cosmetic Act, the Poultry Products Inspection Act, or the Meat Inspection Act. (m) Food includes human food, substances migrating to food from food-contact articles, pet food, and animal feed. [41 FR 38644, Sept. 10, 1976, as amended at 42 FR 55206, Oct. 14, 1977] (a) Over the years the Food and Drug Administration has given informal written opinions to inquirers as to the safety of articles intended for use as components of, or in contact with, food. Prior to the enactment of the Food Additives Amendment of 1958 (Pub. L. 85–929, Sept. 6, 1958), these opinions were given pursuant to section 402(a)(1) of the Federal Food, Drug, and Cosmetic Act, which reads in part: “A food shall be deemed to be adulterated if it bears or contains any poisonous or deleterious substance which may render it injurious to health”. (b) Since enactment of the Food Additives Amendment, the Food and Drug Administration has advised such inquirers that an article: (1) Is a food additive within the meaning of section 201(s) of the act; or (2) Is generally recognized as safe (GRAS); or (3) Has prior sanction or approval under that amendment; or (4) Is not a food additive under the conditions of intended use. (c) In the interest of the public health, such articles which have been considered in the past by the Food and Drug Administration to be safe under the provisions of section 402(a)(1), or to be generally recognized as safe for their intended use, or to have prior sanction or approval, or not to be food additives under the conditions of intended use, must be reexamined in the light of current scientific information and current principles for evaluating the safety of food additives if their use is to be continued. (d) Because of the time span involved, copies of many of the letters in which the Food and Drug Administration has expressed an informal opinion concerning the status of such articles may no longer be in the file of the Food and Drug Administration. In the absence of information concerning the names and uses made of all the articles referred to in such letters, their safety of use cannot be reexamined. For this reason all food additive status opinions of the kind described in paragraph (c) of this section given by the Food and Drug Administration are hereby revoked. (e) The prior opinions of the kind described in paragraph (c) of this section will be replaced by qualified and current opinions if the recipient of each such letter forwards a copy of each to the Department of Health and Human Services, Food and Drug Administration, Center for Veterinary Medicine, Office of Surveillance and Compliance (HFV–200), 7500 Standish Pl., Rockville, MD 20855, along with a copy of his letter of inquiry, on or before July 23, 1970. (f) This section does not apply to food additive status opinion letters pertaining to articles that were considered by the Food and Drug Administration to be food additives nor to articles included in regulations in this Subchapter E if the articles are used in accordance with the requirements of such regulations. [41 FR 38644, Sept. 10, 1976, as amended at 54 FR 18281, Apr. 28, 1989; 57 FR 6476, Feb. 25, 1992] Regulations providing for the use of food packaging materials as prior sanctioned in part 181 of this chapter are incorporated in Subchapter E as applicable to packaging materials used for animal feed and pet food. [42 FR 14091, Mar. 15, 1977] Regulations providing for the use of food packaging materials in parts 174 through 179 of this chapter are incorporated in Subchapter E as applicable to packaging materials used for animal feed and pet food. [42 FR 14091, Mar. 15, 1977] (a) The Commissioner upon his own initiative may propose the issuance of a regulation prescribing, with respect to any particular use of a food additive, the conditions under which such additive may be safely used. Notice of such proposal shall be published in the (b) Action upon a proposal made by the Commissioner shall proceed as provided in part 10 of this chapter. [41 FR 38644, Sept. 10, 1976, as amended at 42 FR 4717, Jan. 25, 1977; 42 FR 15675, Mar. 22, 1977] A food additive or food containing a food additive intended for investigational use by qualified experts shall be exempt from the requirements of section 409 of the act under the following conditions: (a) If intended for investigational use in vitro or in laboratory research animals, it bears a label which states prominently, in addition to the other information required by the act, the warning:
Caution. Contains a new food additive for investigational use only in laboratory research animals or for tests in vitro. Not for use in humans. (b) If intended for use in animals other than laboratory research animals and if the edible products of the animals are to be marketed as food, permission for the marketing of the edible products as food has been requested by the sponsor, and authorization has been granted by the Food and Drug Administration in accordance with §511.1 of this chapter or by the Department of Agriculture in accordance with 9 CFR 309.17, and it bears a label which states prominently, in addition to the other information required by the act, the warning:
Caution. Contains a new food additive for use only in investigational animals. Not for use in humans. Edible products of investigational animals are not to be used for food unless authorization has been granted by the U.S. Food and Drug Administration or by the U.S. Department of Agriculture. (c) If intended for nonclinical laboratory studies in food-producing animals, the study is conducted in compliance with the regulations set forth in part 58 of this chapter. [41 FR 38644, Sept. 10, 1976, as amended at 43 FR 60023, Dec. 22, 1978] (a) Food additives that cause similar or related pharmacological effects will be regarded as a class, and in the absence of evidence to the contrary, as having additive toxic effects and will be considered as related food additives. (b) Tolerances established for such related food additives may limit the amount of a common component that may be present, or may limit the amount of biological activity (such as cholinesterase inhibition) that may be present or may limit the total amount of related food additives that may be present. (c) Where food additives from two or more chemicals in the same class are present in or on a food, the tolerance for the total of such additives shall be the same as that for the additive having the lowest numerical tolerance in this class, unless there are available methods that permit quantitative determination of the amount of each food additive present or unless it is shown that a higher tolerance is reasonably required for the combined additives to accomplish the physical or technical effect for which such combined additives are intended and that the higher tolerance will be safe. (d) Where residues from two or more additives in the same class are present in or on a food and there are available methods that permit quantitative determination of each residue, the quantity of combined residues that are within the tolerance may be determined as follows: (1) Determine the quantity of each residue present. (2) Divide the quantity of each residue by the tolerance that would apply if it occurred alone, and multiply by 100 to determine the percentage of the permitted amount of residue present. (3) Add the percentages so obtained for all residues present. (4) The sum of the percentages shall not exceed 100 percent. When pesticide chemical residues occur in processed foods due to the use of raw agricultural commodities that bore or contained a pesticide chemical in conformity with an exemption granted or a tolerance prescribed under section 408 of the act, the processed food will not be regarded as adulterated so long as good manufacturing practice has been followed in removing any residue from the raw agricultural commodity in the processing (such as by peeling or washing) and so long as the concentration of the residue in the processed food when ready to eat is not greater than the tolerance prescribed for the raw agricultural commodity. But when the concentration of residue in the processed food when ready to eat is higher than the tolerance prescribed for the raw agricultural commodity, the processed food is adulterated unless the higher concentration is permitted by a tolerance obtained under section 409 of the act. For example, if fruit bearing a residue of 7 parts per million of DDT permitted on the raw agricultural commodity is dried and a residue in excess of 7 parts per million of DDT results on the dried fruit, the dehydrated fruit is adulterated unless the higher tolerance for DDT is authorized by the regulations in this part. Food that is itself ready to eat, and which contains a higher residue than allowed for the raw agricultural commodity, may not be legalized by blending or mixing with other foods to reduce the residue in the mixed food below the tolerance prescribed for the raw agricultural commodity. (a) In reaching a decision on any petition filed under section 409 of the act, the Commissioner will give full consideration to the specific biological properties of the compound and the adequacy of the methods employed to demonstrate safety for the proposed use, and the Commissioner will be guided by the principles and procedures for establishing the safety of food additives stated in current publications of the National Academy of Sciences-National Research Council. A petition will not be denied, however, by reason of the petitioner's having followed procedures other than those outlined in the publications of the National Academy of Sciences-National Research Council if, from available evidence, the Commissioner finds that the procedures used give results as reliable as, or more reliable than, those reasonably to be expected from the use of the outlined procedures. In reaching a decision, the Commissioner will give due weight to the anticipated levels and patterns of consumption of the additive specified or reasonably inferable. For the purposes of this section, the principles for evaluating safety of additives set forth in the above-mentioned publications will apply to any substance that may properly be classified as a food additive as defined in section 201(s) of the act. (b) Upon written request describing the proposed use of an additive and the proposed experiments to determine its safety, the Commissioner will advise a person who wishes to establish the safety of a food additive whether he believes the experiments planned will yield data adequate for an evaluation of the safety of the additive. (a) General recognition of safety may be based only on the views of experts qualified by scientific training and experience to evaluate the safety of substances directly or indirectly added to food. The basis of such views may be either (1) scientific procedures or (2) in the case of a substance used in food prior to January 1, 1958, through experience based on common use in food. General recognition of safety requires common knowledge about the substance throughout the scientific community knowledgeable about the safety of substances directly or indirectly added to food. (b) General recognition of safety based upon scientific procedures shall require the same quantity and quality of scientific evidence as is required to obtain approval of a food additive regulation for the ingredient. General recognition of safety through scientific procedures shall ordinarily be based upon published studies which may be corroborated by unpublished studies and other data and information. (c) General recognition of safety through experience based on common use in food prior to January 1, 1958, may be determined without the quantity or quality of scientific procedures required for approval of a food additive regulation. General recognition of safety through experience based on common use in food prior to January 1, 1958, shall ordinarily be based upon generally available data and information. An ingredient not in common use in food prior to January 1, 1958, may achieve general recognition of safety only through scientific procedures. (d) The food ingredients listed as GRAS in part 582 of this chapter do not include all substances that are generally recognized as safe for their intended use in food. Because of the large number of substances the intended use of which results or may reasonably be expected to result, directly or indirectly, in their becoming a component or otherwise affecting the characteristics of food, it is impracticable to list all such substances that are GRAS. A food ingredient of natural biological origin that has been widely consumed for its nutrient properties in the United States prior to January 1, 1958, without known detrimental effects, which is subject only to conventional processing as practiced prior to January 1, 1958, and for which no known safety hazard exists, will ordinarily be regarded as GRAS without specific inclusion in part 582 of this chapter. (e) A food ingredient that is not GRAS or subject to a prior sanction requires a food additive regulation promulgated under section 409 of the act before it may be directly or indirectly added to food. (f) A food ingredient that is listed as GRAS in part 582 of this chapter shall be regarded as GRAS only if, in addition to all the requirements in the applicable regulation, it also meets all of the following requirements: (1) It complies with any applicable specifications, or in the absence of such specifications, shall be of a purity suitable for its intended use. (2) It performs an appropriate function in the food or food-contact article in which it is used. (3) It is used at a level no higher than necessary to achieve its intended purpose in that food or, if used as a component of a food-contact article, at a level no higher than necessary to achieve its intended purpose in that article. (g) New information may at any time require reconsideration of the GRAS status of a food ingredient. Any change in status shall be accomplished pursuant to §570.38. (h) If a substance is affirmed as GRAS pursuant to §570.35 and listed in a regulation with no limitation other than good manufacturing practice, it shall be regarded as GRAS if its conditions of use are not significantly different from those reported in the regulation as the basis on which the GRAS status of the substance was affirmed. If the conditions of use are significantly different, such use of the substance may not be GRAS. In such case a manufacturer may not rely on the regulation as authorizing the use but must independently establish that the use is GRAS or must use the substance in accordance with a food additive regulation. (i) If an ingredient is affirmed as GRAS pursuant to §570.35 and listed in a regulation with specific limitation(s), it may be used in food only within such limitation(s) (including the category of food(s), the functional use(s) of the ingredient, and the level(s) of use). Any use of such and ingredient not in full compliance with each such established limitation shall require a food additive regulation. (j) Pursuant to §570.35, a food ingredient may be affirmed as GRAS and listed in a regulation for a specific use(s) without a general evaluation of use of the ingredient. In addition to the use(s) specified in the regulation, other uses of such an ingredient may also be GRAS. Any affirmation of GRAS status for a specific use(s), without a general evaluation of use of the ingredient, is subject to reconsideration upon such evaluation. [42 FR 55206, Oct. 14, 1977] (a) The Commissioner, either on his initiative or on the petition of an interested person, may affirm the GRAS status of substances that directly or indirectly become components of food. (b)(1) If the Commissioner proposes on his own initiative that a substance is entitled to affirmation as GRAS, he will place all of the data and information on which he relies on public file in the office of the Division of Dockets Management and will publish in the (2) The (3) The Commissioner will evaluate all comments received. If he concludes that there is convincing evidence that the substance is GRAS as defined in §570.3(k), he will publish a notice in the (4) If, after evaluation of the comments, the Commissioner concludes that there is a lack of convincing evidence that the substance is GRAS and that it should be considered a food additive subject to section 409 of the act, he shall publish a notice thereof in the (c)(1) Persons seeking the affirmation of GRAS status of substances as provided for in §570.30(e), except those subject to the NAS-NRC GRAS list survey (36 FR 20546), shall submit a petition for GRAS affirmation pursuant to part 10 of this chapter. Such petition shall contain information to establish that the GRAS criteria as set forth in §570.30(b) have been met, in the following form: (i) Description of the substance, including: (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 material, including arsenic and heavy metals. (Recommendation for any change in the Food Chemicals Codex monograph should be included where applicable.) (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 purposes. (iii) Methods for detecting the substance in food, including: (a) References to qualitative and quantitative methods for determining the substance(s) in food, including the type of analytical procedures used. (b) Sensitivity and reproducibility of such method(s). (iv) Information to establish the safety and functionality of the substance in food. Published scientific literature, evidence that the substance is identical to a GRAS counterpart of natural biological origin, and other data may be submitted to support safety. Any adverse information or consumer complaints shall be included. Complete bibliographic references shall be provided where a copy of the article is not provided. (v) A statement signed by the person responsible for the petition that to the best of his knowledge it is a representative and balanced submission that includes unfavorable information, as well as favorable information, known to him pertinent to the evaluation of the safety and functionality of the substance. (vi) If nonclinical laboratory studies are involved, additional information and data submitted in support of filed petitions shall include, with respect to each nonclinical study, either a statement that the study was conducted in compliance with the requirements set forth in part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance. (vii) [Reserved] (viii) A claim for categorical exclusion under §25.30 or 25.32 of this chapter or an environmental assessment under §25.40 of this chapter. (2) Within 30 days after the date of filing the petition, the Commissioner will place the petition on public file in the Division of Dockets Management and will publish a notice of filing in the (3) The notice of filing in the (4) The Commissioner will evaluate the petition and all available information including all comments received. If the petition and such information provide convincing evidence that the substance is GRAS as defined in §570.3, he will publish an order in the (5) If, after evaluation of the petition and all available information, the Commissioner concludes that there is a lack of convincing evidence that the substance is GRAS and that it should be considered a food additive subject to section 409 of the act, he shall publish a notice thereof in the (6) The notice of filing in the [41 FR 38644, Sept. 10, 1976, as amended at 42 FR 4717, Jan. 25, 1977; 42 FR 15675, Mar. 22, 1977; 42 FR 55207, Oct. 10, 1977; 50 FR 7517, Feb. 22, 1985; 50 FR 16668, Apr. 26, 1985; 54 FR 18281, Apr. 28, 1989; 62 FR 40600, July 29, 1997] (a) The Commissioner may, in accordance with §570.35 (b)(4) or (c)(5), publish a notice in the (b)(1) The Commissioner, on his own initiative or on the petition of any interested person, pursuant to part 10 of this chapter, may issue a notice in the (2) The (3) The Commissioner will evaluate all comments received. If he concludes that there is a lack of convincing evidence that the substance is GRAS or is otherwise exempt from the definition of a food additive in section 201(s) of the act, he will publish a notice thereof in the (c) A (1) It may promulgate a food additive regulation governing use of the additive. (2) It may promulgate an interim food additive regulation governing use of the additive. (3) It may require discontinuation of the use of the additive. (4) It may adopt any combination of the above three approaches for different uses or levels of use of the additive. (d) If the Commissioner of Food and Drugs is aware of any prior sanction for use of the substance, he will concurrently propose a separate regulation covering such use of the ingredient under this subchapter E. If the Commissioner is unaware of any such applicable prior sanction, the proposed regulation will so state and will require any person who intends to assert or rely on such sanction to submit proof of its existence. Any regulation promulgated pursuant to this section constitutes a determination that excluded uses would result in adulteration of the food in violation of section 402 of the act, and the failure of any person to come forward with proof of such an applicable prior sanction in response to the proposal will constitute a waiver of the right to assert or rely on such sanction at any later time. The notice will also constitute a proposal to establish a regulation under this subchapter E., incorporating the same provisions, in the event that such a regulation is determined to be appropriate as a result of submission of proof of such an applicable prior sanction in response to the proposal. [41 FR 38644, Sept. 10, 1976, as amended at 42 FR 4717, Jan. 25, 1977; 42 FR 15675, Mar. 22, 1977; 42 FR 55207, Oct. 14, 1977; 54 FR 18281, Apr. 28, 1989]
Title 21: Food and Drugs
PART 570—FOOD ADDITIVES
Section Contents
§ 570.3 Definitions.
§ 570.6 Opinion letters on food additive status.
§ 570.13 Indirect food additives resulting from packaging materials prior sanctioned for animal feed and pet food.
§ 570.14 Indirect food additives resulting from packaging materials for animal feed and pet food.
§ 570.15 Adoption of regulation on initiative of Commissioner.
§ 570.17 Exemption for investigational use and procedure for obtaining authorization to market edible products from experimental animals.
§ 570.18 Tolerances for related food additives.
§ 570.19 Pesticide chemicals in processed foods.
§ 570.20 General principles for evaluating the safety of food additives.
§ 570.30 Eligibility for classification as generally recognized as safe (GRAS).
§ 570.35 Affirmation of generally recognized as safe (GRAS) status.
§ 570.38 Determination of food additive status.
Subpart A—General Provisions
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§ 570.3 Definitions.
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§ 570.6 Opinion letters on food additive status.
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§ 570.13 Indirect food additives resulting from packaging materials prior sanctioned for animal feed and pet food.
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§ 570.14 Indirect food additives resulting from packaging materials for animal feed and pet food.
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§ 570.15 Adoption of regulation on initiative of Commissioner.
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§ 570.17 Exemption for investigational use and procedure for obtaining authorization to market edible products from experimental animals.
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§ 570.18 Tolerances for related food additives.
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§ 570.19 Pesticide chemicals in processed foods.
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Subpart B—Food Additive Safety
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§ 570.20 General principles for evaluating the safety of food additives.
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§ 570.30 Eligibility for classification as generally recognized as safe (GRAS).
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§ 570.35 Affirmation of generally recognized as safe (GRAS) status.
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§ 570.38 Determination of food additive status.
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