(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 of the species to which the substance is intended to be fed (and, for food-producing animals fed with such substance, also means a substantial history of consumption by humans consuming human foods derived from those food-producing animals), prior to January 1, 1958.

(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 the application of scientific data (including, as appropriate, data from human, animal, analytical, or other scientific studies), information, and methods, whether published or unpublished, as well as the application of scientific principles, appropriate to establish the safety of a substance under the conditions of its intended use.

(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 conditions of its intended 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 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.

(n) Food-producing animal means an animal used to produce human food.

(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.

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.

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.

(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 Federal Register and shall state the reasons for the proposal.

(b) Action upon a proposal made by the Commissioner shall proceed as provided in part 10 of this chapter.

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:

(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:

(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.

(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.