(b) In view of the hazards involved when tannic acid is used in barium enemas, any shipments of tannic acid labeled to come within the exemptions under 502(f) of the Act containing such phrases as: "Caution: For manufacturing, processing, or repackaging," "For prescription compounding," or "Diagnostic reagent-For professional use only" will be regarded by the Commissioner of Food and Drugs as misbranded within the meaning of section 502(f) of the Federal Food, Drug, and Cosmestic Act unless the label and the labeling bear conspicuously a warning to the effect: "Warning-Not for use in enemas."

(c) Any tannic acid intended for use by man and found within the jurisdiction of the Federal Food, Drug, and Cosmetic Act labeled contrary to this section after 60 days from the date of its publication in the FEDERAL REGISTER may be made the subject of regulatory proceedings. (Sec. 502, 52 Stat. 1051, as amended; 21 U.S.C. 352) [29 F.R. 3621, Mar. 21, 1964] §3.13 Grain seed treated with poisonous substances; color identification to prevent adulteration of human and animal food.

(a) In recent years there has developed increasing use of poisonous treatments on seed for fungicidal and other purposes. Such treated seed, if consumed, presents a hazard to humans and livestock. It is not unusual for stocks of such treated food seeds to remain on hand after the planting season has passed. Despite the cautions required by the Federal Seed Act (53 Stat. 1275, as amended 72 Stat. 476, 7 U.S.C. 1551 et seq.) in the labeling of the treated seed, the Food and Drug Administration has encountered many cases where such surplus stocks of treated wheat, corn, oats, rye, barley, and sorghum seed had been mixed with untreated seed and sent to market for food or feed use. This has resulted in livestock injury and in legal actions under the Federal Food, Drug, and Cosmetic Act against large quantities of food adulterated through such admixture of poisonous treated seeds with good food. Criminal cases were brought against some firms and individuals. Where the treated seeds are prominently colored, buyers and users or processors of agricultural food seed for food purposes are able to detect the admixture of the poisonous seed and thus reject the lots; but most such buyers, users, and processors do not have the facilities or scien

tific equipment to determine the presence of the poisonous chemical at the time crops are delivered, in cases where the treated seeds have not been so colored. A suitable color for this use is one that is in sufficient contrast to the natural color of the food seed as to make admixture of treated, denatured seeds with good food easily apparent, and is so applied that it is not readily removed.

(b) On and after December 31, 1964, the Food and Drug Administration will regard as adulterated any interstate shipment of the food seeds wheat, corn, oats, rye, barley, and sorghum bearing a poisonous treatment in excess of a recognized tolerance or treatment for which no tolerance or exemption from tolerance is recognized in regulations promulgated pursuant to section 408 of the Federal Food, Drug, and Cosmetic Act, unless such seeds have been adequately denatured by a suitable color to prevent their subsequent inadvertent use as food for man or feed for animals.

(c) Attention is called to the labeling requirements of the Federal Hazardous Substances Labeling Act, where applicable to denatured seeds in packages suitable for household use.

(Secs. 402 (a), 408, 52 Stat. 1046 as amended; 68 Stat. 511; 21 U.S.C. 342 (a), 348; sec. 2(1) (1), 74 Stat. 372; 15 U.S.C. 1261) [28 F.R. 11925, Nov. 8, 1963]

§ 3.14 Notice to manufacturers and distributors of foods and drugs containing artificial sweeteners.

Chronic-toxicity studies conducted by the Department of Health, Education, and Welfare show that the artificial sweeteners dulcin (also known as sucrol, or 4-ethoxyphenylurea, or paraphenetolcarbamide) and P-4000 (also known as 1-n-propoxy-2-amino-4-nitrobenzene) cause injury to rats when fed at relatively low levels for approximately 2 years. Consequently, the Secretary of Health, Education, and Welfare regards these chemicals as poisonous substances which have no place in any food.

Pending further evaluation of available data, it is not possible to state the conditions under which dulcin or P-4000 would render a drug in which it is used dangerous to health. Since other artificial sweeteners are available which have a much greater margin of safety in chronic-toxicity studies, the use of dulcin and P-4000 as sweetners of drugs is to be discouraged.

[20 F.R. 9545, Dec. 20, 1955]

§3.15 Potassium salt preparations intended for oral ingestion by man.

(a) The Food and Drug Administration will initiate no regulatory action with respect to the continued marketing of coated tablets containing potassium chloride or other potassium salts which supply 100 milligrams or more of potassium per tablet provided all the following conditions are met:

(1) Within 30 days from the date of publication of this statement of policy in the FEDERAL REGISTER:

(i) The labeling of the drug bears the prescription caution statement quoted in section 503(b) (4) of the Federal Food, Drug, and Cosmetic Act;

(ii) The labeling on or within the package from which the drug is to be dispensed bears adequate information for its use by practitioners in accord with the "full disclosure" labeling requirements of § 1.106(b) of this chapter, including the following warning statement: "Warning-There have been several reports, published and unpublished, concerning nonspecific small-bowel lesions consisting of stenosis, with or without ulceration, associated with the administration of enteric-coated thiazides with potassium salts. These lesions may occur with enteric-coated potassium tablets alone or when they are used with nonenteric-coated thiazides, or certain other oral diuretics. These small-bowel lesions have caused obstruction, hemorrhage, and perforation. Surgery was frequently required and deaths have occurred. Based on a large survey of physicians and hospitals, both United States and foreign, the incidence of these lesions is low, and a causal relationship in man has not been definitely established. Available information tends to implicate enteric-coated potassium salts, although lesions of this type also occur spontaneously. Therefore, coated potassium-containing formulations should be administered only when indicated, and should be discontinued immediately if abdominal pain, distention, nausea, vomiting, or gastrointestinal bleeding occur. Coated potassium tablets should be used only when adequate dietary supplementation is not practicable."

(Although the warning statement includes references to enteric-coated potassium salt preparations, it applies to any capsule or coated tablet of a potassium salt intended for oral ingestion without prior dilution with an adequate

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volume of liquid to preclude gastrointestinal injury.)

(iii) Any other labeling or additional advertising for the drug conforms to the labeling described in subdivision (ii) of this subparagraph, in accord with §§ 1.105 and 1.106(b) of this chapter.

(2) Within 90 days from the date of publication of this statement of policy in the FEDERAL REGISTER, the manufacturer, packer, or distributor of the drug shall submit a new-drug application containing satisfactory information of the kind required by Items 2, 3, 4, 6, 7, and 9 of the new-drug application form contained in § 130.4 (c) of this chapter, with appropriate labeling as described in this paragraph.

(b) The Food and Drug Administration may initiate regulatory proceedings after 30 days from the date of publication of this section, with respect to the marketing of uncoated tablets containing potassium chloride or other potassium salts which supply 100 milligrams or more of potassium per tablet or with respect to liquid preparations containing potassium chloride or other potassium salts which supply 20 milligrams or more of potassium per milliliter, labeled or intended for human use, unless all the following conditions are met:

(1) The labeling of the drug bears the prescription caution statement quoted in section 503(b) (4) of the Federal Food, Drug, and Cosmetic Act; and

(2) The labeling on or within the package from which the drug is to be dispensed bears adequate information for its use by practitioners in accord with the "full disclosure" labeling requirements of § 1.106(b) of this chapter, including a recommendation that patients be directed to disslove any such tablets in an appropriate amount of liquid and to dilute any such liquid preparations adequately to assure against gastrointestinal injury associated with the oral ingestion of concentrated potassium salt preparations.

(Secs. 502(f), 503(b)(4), 505; 52 Stat. 1051, 1052; 21 U.S.C. 352 (f), 353 (b), 355) [30 F.R. 5790, Apr. 24, 1965; 30 F.R. 6071, Apr. 29, 1965] §3.16 Use of ox bile from condemned

livers from slaughtered animals in the manufacture of drugs. Conferences have recently been held between members of the Department of Health, Education, and Welfare and representatives of the Agricultural Research Service, Department of Agriculture,

concerning requests made to that agency for the release of ox bile from condemned livers of slaughtered animals for use in the manufacture of certain drugs.

The Secretary of Health, Education, and Welfare has given careful consideration to this problem and has reached the conclusion that no hazard to public health will be involved in the release of such ox bile, after the addition to it of sufficient sodium hydroxide to give the mixture a sodium hydroxide content of not less than 5 percent, the mixture then being allowed to stand at least 24 hours. This Department will not regard as in violation of the provisions of the Federal Food, Drug, and Cosmetic Act such alkalized and aged ox bile, if labeled "Ox Bile and Sodium Hydroxide (or Ox Bile and Sodium Hydroxide Solution). Sodium hydroxide not less than 5 percent by weight. For manufacturing use only." together with a statement of the quantity of contents in the container (for example, "50 gallons") and the name and address of the manufacturer, packer, or shipper.

Bile from the condemned livers of sheep and goats also may be released, under the same conditions as outlined in the preceding paragraph, except that the words "Sheep Bile" or "Goat Bile," as the case may be, shall be substituted for the words "Ox Bile" upon the label. In the case of mixtures of bile from any two or all three of the sources mentioned, the label shall indicate the sources of such bile.

[20 F.R. 9541, Dec. 20, 1955, as amended at 22 F.R. 10685, Dec. 25, 1957]

§3.17 Labeling of oleomargarine or margarine.

The Federal Food, Drug, and Cosmetic Act was amended by Public Law 459, 81st Congress (64 Stat. 20) on colored oleomargarine or margarine by adding thereto a new section numbered 407. Among other things, this section requires that there appear on the label of the package the word "oleomargarine" or "margarine" in type or lettering at least as large as any other type or lettering on the label, and a full and accurate statement of all the ingredients contained in such oleomargarine or margarine. It provides that these requirements "shall be in addition to and not in lieu of any of the other requirements of this Act."

(a) Under section 403 (g) of the Federal Food, Drug, and Cosmetic Act, any article that is represented as or

purports to be oleomargarine or margarine must conform to the definition and standard of identity for oleomargarine or margarine promulgated under section 401 of the act (Part 45 of this chapter), and its label must bear the name "oleomargarine" or "margarine."

(b) The identity standard for oleomargarine or margarine applies to both the uncolored and the colored article. Although this standard does not require that all permitted optional ingredients be declared on the label, the amendment to the Federal Food, Drug, and Cosmetic Act made by Public Law 459, 81st Congress, requires the labels on packages of colored oleomargarine or margarine to bear "a full and accurate statement of all the ingredients contained in such oleomargarine or margarine." The optional ingredients permitted by the identity standard for oleomargarine or margarine and the names by which we believe such ingredients, when present, should be declared in order to constitute "a full and accurate statement" are set forth below:

(1) The rendered fat or oil, or stearin derived therefrom (any or all of which may be hydrogenated), of cattle, sheep, swine, or goats, or any combination of two or more such articles-to be declared by the name of the specific animal fat, oil, or stearin, for example, "beef fat." If the animal fat or oil is hydrogenated the name should include the word "hydrogenated" or "hardened." Where combinations are used, the names are to be arranged in order of predominance, with the animal fat, oil, or stearin present in greatest proportion named first.

(2) Any vegetable food fat or oil, or oil or stearin derived therefrom (any or all of which may be hydrogenated), or any combination of two or more such articles-to be declared by the name of the specific vegetable food fat, oil, or stearin, for example "cottonseed oil" or "soybean oil." If the vegetable fats or oils present are hydrogenated, the declaration should include the word "hydrogenated" or "hardened," for example, "hydrogenated cottonseed oil" or "hardened cottonseed oil." If two or more vegetable food fats or oils are used they are to be named in order of predominance with the one present in greatest proportion named first in the series, as, for example, "cottonseed oil, soybean oil, and corn oil."

(3) The optional ingredients cream, milk, skim milk, nonfat dry milk and water, ground soybeans and water, butter, and salt should be declared by those terms.

(4) Artificial color and artificial flavor should be declared as such by the terms prescribed in the identity standard for oleomargarine or margarine (Part 45 of this chapter). They need not be de

clared additionally by the names of the specific colors or flavors.

(5) The presence of sodium benzoate or benzoic acid should be declared as prescribed by the identity standard for oleomargarine or margarine.

(6) The optional ingredient vitamin A added in an essential carrier should be declared as "vitamin A added" or "with added vitamin A.”

(7) The optional ingredient vitamin D should be declared as "vitamin D added" or "with added vitamin D."

(8) The optional emulsifying ingredients lecithin, mono- or diglycerides and sodium sulfo-acetate derivatives of mono- or diglycerides should be declared by those terms.

(9) The presence of citric acid, isopropyl citrate, and stearyl citrate should be declared as prescribed by the identity standard for oleomargarine or margarine.

(10) The statement of all the ingredients contained in colored oleomargarine or colored margarine is subject to the requirements pertaining to conspicuousness in section 403 (f) of the act.

(c) In considering the requirement that the word "oleomargarine” or “margarine" be in type or lettering at least as large as any other type or lettering on the label, it must be borne in mind that at least three factors are involved-the height of each letter, the area occupied by each letter as measured by a closely fitting rectangle drawn around it, and the boldness of letters or breadth of the lines forming the letters. The type or lettering used should meet the following tests:

(1) The height of each letter in the word "oleomargarine" or "margarine" should equal or exceed the height of any other letter elsewhere on the label.

(2) The area of the closely fitting rectangle with respect to any of the letters in the word "oleomargarine" or "margarine" should equal or exceed the area of such rectangle applied to the same or a corresponding letter elsewhere on the label.

(3) The letters in the word "oleomargarine" or "margarine" should be equal to or exceed in prominence and boldness, such as breadth of lines forming the letters, the same or corresponding letters elsewhere on the label.

(d) All oleomargarine or margarine containing the optional ingredients vitamin A, vitamin D, or both is subject to the regulations regarding labeling requirements pertaining to foods for special dietary use, as promulgated under the provisions of section 403 (j) of the act (Part 125 of this chapter).

(e) The word "oleomargarine" or "margarine" (and thus the other information called for by the statute) should appear on each panel of the package label that might reasonably be selected by the grocer for display purposes at the point of sale.

(f) The amendment covering colored oleomargarine or colored margarine states that, "for the purposes of

section 407 of the Federal Food, Drug, and Cosmetic Act, as amended, the term 'oleomargarine' or 'margarine' includes: (1) All substances, mixtures, and compounds known as oleomargarine or margarine; (2) all substances, mixtures, and compounds which have a consistence similar to that of butter and which contain any edible oils or fats other than milk fat if made in imitation or semblance of butter." Notwithstanding the difference between this definition and the definition and standard of identity for oleomargarine or margarine promulgated under section 401 of the act, it was the clear intent of Congress that any article which is represented as or purports to be oleomargarine or margarine is misbranded if it fails to comply with the definition and standard of identity for oleomargarine or inargarine even though it may meet the statutory definition.

(g) Section 407 (a) states that "Colored oleomargarine or colored margarine which is sold in the same State or Territory in which it is produced shall be subject in the same manner and to the same extent to the provisions of this act as if it had been introduced in interstate commerce."

(h) Section 407 (b) (4) requires that each part of the contents of the package be "contained in a wrapper which bears the word 'oleomargarine' or ‘margarine' in type or lettering not smaller than 20point type." The Food and Drug Administration interprets this to mean that

the height of the actual letters is no less than 20 points, or 20/72 of 1 inch.

(i) The wrappers on the subdivisions of oleomargarine or margarine contained within the packages sold at retail are labels within the meaning of section 201 (k) and should contain all of the label information required by sections 403 and pertaining to foods for special dietary use, as promulgated under the provisions 407 of the Federal Food, Drug, and Cosmetic Act, just as in the case of 1-pound cartons.

(Sec. 407, 64 Stat. 20; 21 U. S. C. 347) [23 F. R. 6552, Aug. 23, 1958]

§3.18 Drugs for use in milk-producing animals; labeling.

(a) Section 146.14 of this chapter, covering certain antibiotic and antibioticcontaining drugs intended for use in milk-producing animals, applies only to preparations containing antibiotics subject to certification under section 507 of the Federal Food, Drug, and Cosmetic Act and is intended to prevent contamination of milk. The public-health factors involved, however, apply equally to any articles administered to milk-producing animals, even though those articles are not antibiotics subject to certification.

(b) The Food and Drug Administration considers that non-certifiable antibiotics and other potent drugs, as well as any preparation containing these, if labeled with directions for use in milkproducing animals, will be misbranded under section 502(f) (2) of the act unless their labeling bears appropriate warnings to avoid uses that would result in contamination of milk.

(c) It is the position of the Food and Drug Administration that the labeling for such preparations should bear a clear warning that either:

(1) The article should not be administered to animals producing milk, since to do so would result in contamination of the milk; or

(2) The label should bear a warning that the milk should be discarded for

hours after the latest use, the blank to be filled in with the number of hours (not to exceed 96) that the manufacturer has determined by appropriate investigation is needed to insure that the milk will not carry residues resulting from use of the preparation. If the use of the preparation as recommended does not result in contamination of the milk,

neither of the above warning statements is required.

(Sec. 502(f), 52 Stat. 1051; 21 U.S.C. 352(f)). [25 F.R. 8321, Aug. 31, 1960]

§3.19

Notice to manufacturers, packers, and distributors of pasteurized process cheese, pasteurized blended cheese, pasteurized process cheese food, pasteurized process cheese spread, and related foods.

(a) Definitions and standards of identity have recently been promulgated under the authority of the Federal Food, Drug, and Cosmetic Act for a number of foods made in part from cheese, including pasteurized process cheese; pasteurized process cheese with fruits, vegetables, or meats; pasteurized blended cheese; pasteurized process cheese food; pasteurized process cheese spread, and related foods. These standards prescribe the name for each such food. The act requires that this name appear on the label. Many of these names consist of several words. In the past it has been the practice of some manufacturers to subordinate the words "pasteurized," "blended," "process," "food," and "spread" to give undue prominence to the word "cheese" and to words naming the variety of cheese involved.

(b) When placing the names of these foods on labels so as to comply with the requirements of section 403(a), (f), and (g) of the act, all the words forming the name specified by a definition and standard of identity should be given equal prominence. This can readily be accomplished by printing the specified name of the food in letters of the same size, color, and style of type, and with the same background.

(c) Where the names of optional ingredients are required to appear on the label, the designations of all such ingredients should be given equal prominence. The names of the optional ingredients should appear prominently and conspicuously but should not be displayed with greater prominence than the name of the food. The word "contains" may precede the names of the optional ingredients, and when so used will not be considered as intervening printed matter between name of food and name of optional ingredients required to be placed on the label.

(d) Where a manufacturer elects to include a label statement of fat and moisture content, the declaration should be on the basis of the food as marketed.