cure, mitigation, treatment, or prevention of disease, or in affecting the structure or any function of the body.

Manufacturers have heretofore taken advantage of § 1.106 (b) of this chapter, permitting omission of directions for use when the label bears the prescription legend. Section 1.106 (b) (3) of this chapter requires that the labeling of the drug, which may include brochures readily available to licensed practitioners, bear information as to the use of the drug by practitioners licensed by law to administer it. Obviously, information adequate for the use of an inert glandular preparation is not available to practitioners licensed by law.

The Department of Health, Education, and Welfare is of the opinion that inert glandular materials may not be exempted from the requirements of section 502 (f) (1) of the act that they bear adequate directions for use; and, accordingly, that their labeling must include, among other things, representations as to the conditions for which such articles are intended to be used or as to the structure or function of the human body that they are intended to affect. Since any such representations offering these articles for use as drugs would be false or misleading, such articles will be considered to be misbranded if they are distributed for use as drugs.

The amended regulations provide also that in the case of drugs intended for parenteral administration there shall be no exemption from the requirement that their labelings bear adequate directions for use. Such inert glandular materials for parenteral use are therefore subject to the same comment as applies to those intended for oral administration.

[20 F.R. 9542, Dec. 20, 1955, as amended at 22 F.R. 10685, Dec. 25, 1957]

§ 3.4 Notice to manufacturers, packers, and distributors of drugs for internal use which contain mineral oil.

In the past few years research studies have altered medical opinion as to the usefulness and harmfulness of mineral oil in the human body. These studies have indicated that when mineral oil is used orally near mealtime it interferes with absorption from the digestive tract of provitamin A and the fat-soluble vitamins A, D, and K, and consequently interferes with the utilization of calcium and phosphorus, with the result that the user is left liable to deficiency diseases.

When so used in pregnancy it predisposes to hemorrhagic disease of the newborn.

There is accumulated evidence that the indiscriminate administration of mineral oil to infants may be followed by aspiration of the mineral oil and subsequent "lipoid pneumonia."

In view of these facts, the Department of Health, Education, and Welfare will regard as misbranded under the provisions of the Federal Food, Drug, and Cosmetic Act a drug for oral administration consisting in whole or in part of mineral oil, the labeling of which encourages its use in pregnancy or indicates or implies that such drug is for administration to infants.

The

It is also this Department's view that the act requires the labelings of such drugs to bear a warning against consumption other than at bedtime and against administration to infants. following form of warning is suggested: "Caution: To be taken only at bedtime. Do not use at any other time or administer to infants, except upon the advice of a physician."

This statement of interpretation does not in any way exempt mineral oil or preparations containing mineral oil from complying in all other respects with the requirements of the Federal Food, Drug, and Cosmetic Act.

[20 F.R. 9542, Dec. 20, 1955]

(a) Investigations by the Food and Drug Administration and a number of State regulatory agencies have revealed that incubator reject eggs, removed as infertile or otherwise unhatchable during hatching operations, are being diverted for human food use. Such eggs are regarded as adulterated within the meaning of section 402 (a) (3) of the Federal Food, Drug, and Cosmetic Act (52 Stat. 1046; 21 U.S.C. 342 (a) (3) because they are unfit for food.

(b) The introduction or delivery for introduction into interstate commerce of adulterated eggs is prohibited under section 301 (a) of the aforesaid act (52 Stat. 1042; 21 U. S. C. 331 (a) unless they have been broken, crushed, or smashed and then denatured with kerosene, creolin, or other suitable denaturant to preclude their diversion to human food channels.

(Secs. 301, 402, 52 Stat. 1042, 1046; 21 U. S. C. 331, 342) [23 F. R. 6834, Sept. 5, 1958]

§ 3.6 Notice to importers of Peruvian canned fish.

In collaboration with the United States Department of State and officials of the Government of Peru, the Food and Drug Administration of the Department of Health, Education, and Welfare has made a study in Peru of the canning of bonito and tuna packed for exportation to the United States. The fish known in Peru as bonito constitutes a major portion of the pack. Representative specimens of Peruvian bonito have been identified as the species Sarda chilensis. This confirms previous information that the species of fish constituting the commercial bonito fishery in Peru is the same species of bonito that has been packed in this country in small quantities and sold as bonito, for many years. Minor quantities of another bonito, Sarda velox, are apparently caught in Peruvian waters but do not enter the commercial pack to any significant degree. The bonitos, Sarda chilensis and Sarda velox, are not classified as tuna and under the provisions of the Federal Food, Drug, and Cosmetic Act have never been legally labeled as tuna, but must be labeled as "bonito" or "bonito fish.”

Two species of tuna, "skipjac” (Katsuwonus pelamis) and "yellowfin❞

(Thunnus macropterus), are commercially canned in Peru but constitute a relatively small proportion of the Peruvian pack of canned fish exported to the United States.

Information developed during the investigation in Peru shows that the bonito (Sarda chilensis) can be readily distinguished from the tunas. Consequently no difficulty should be encountered by packers in keeping separate the fish in the two classifications and in properly labeling the canned product before shipment.

The provisions of the Federal Food, Drug, and Cosmetic Act require that importations of canned bonito and canned tuna, when offered for entry into the United States, must bear labels designating the product as "bonito" or as "tuna", as the case may be. Shipments that are unlabeled or mislabeled when offered for entry must be detained and are subject to refusal of admission, with consequent exportation or destruction. [20 F.R. 9542, Dec. 20, 1955]

§3.7 Potassium permanganate preparations as prescription drugs.

(a) There have been a number of reports in the medical literature of serious injuries to women resulting from the misuse of potassium permanganate in an effort to induce abortion. Reports from physicians who have treated such cases show that the injuries are commonly caused by introducing tablets or crystals of potassium permanganate into the vagina. Experience with these cases shows that such use of potassium permanganate is not effective in producing abortion, but that instead the drug produces serious and painful injury to the walls of the vagina, causing ulcers, massive hemorrhage, and infection. Such dangerous and useless employment of potassium permanganate is apparently encouraged among the misinformed by the mistaken idea that the vaginal bleeding caused by the corrosive action of the drug indicates a termination of pregnancy, which it does not.

son.

(b) Potassium permanganate is a strong oxidizing agent, a highly caustic, tissue-destroying chemical, and a poiThere are no circumstances under which crystals and tablets of potassium permanganate constitute safe dosage forms for use in self-medication. It is the consensus of informed medical opinion that the only dosage forms of potassium permanganate known to be safe for use in self-medication are aqueous solutions containing not more than 0.04 percent potassium permanganate. Such solutions are safe for use in self-medication only by external application to the skin.

(c) In view of the very real potentiality for harmful effect, and the actual injuries caused by the misuse of potassium permanganate, the Food and Drug Administration believes that in order adequately to protect the public health:

(1) Potassium permanganate and potassium permanganate tablets intended for human use are drugs subject to section 503 (b) (1) of the Federal Food, Drug, and Cosmetic Act and should be restricted to prescription sale. Such drugs will be regarded as misbranded if at any time prior to dispensing the label fails to bear the legend, "Caution: Federal law prohibits dispensing without prescription."

(2) Potassium permanganate labeled for use as a prescription component in

human drugs under the exemption provided in § 1.106 (k) of this chapter or labeled for manufacturing use under the exemption provided in § 1.106 (1) will be regarded as misbranded unless the label bears the statement, "Caution: Federal law prohibits dispensing without prescription."

(3) These drugs will be regarded as misbranded when intended for veterinary use unless the label bears the legend, "Caution: Federal law restricts this drug to sale by or on the order of a licensed veterinarian"; Provided, however, That this shall not apply to a drug labeled and marketed for veterinary use if such drug contains not more than 50 percent of potassium permanganate and includes other ingredients which make it unsuitable for human use and unlikely that the article would be used in an attempt to induce abortion.

(4) Any preparation of potassium permanganate intended for over-the-counter sale for human use internally or by application to any mucous membranes or for use in the vagina will be regarded as misbranded under the provisions of section 502(f) (1) and (2) and section 502 (j) of the act.

(5) Any other preparation of potassium permanganate intended for overthe-counter sale for human use will be regarded as misbranded under section 502(f) (1) and (2) and section 502 (j) of the act unless, among other things, all of the following conditions are met:

(i) It is an aqueous solution containing not more than 0.04 percent potassium permanganate.

(ii) The label and labeling bear, in juxtaposition with adequate directions for use, clear warning statements designated as "Warning," and to the effect: "Warning-For external use on the skin only. Severe injury may result from Avoid use internally or as a douche. contact with mucous membranes."

(d) The labeling or dispensing of any potassium permanganate preparations intended for drug use within the jurisdiction of the Federal Food, Drug, and Cosmetic Act contrary to this statement after 60 days from the date of its publication in the FEDERAL REGISTER may be made the subject of regulatory proceedings.

(Secs. 502(f) (1), (2), (j), 503 (b) (1), 705(b), 52 Stat. 1050, 1051, 1052, as amended, 1057; 21 U.S.C. 352(f) (1), (2), (j), 353(b) (1), 375(b)) [25 F.R. 8073, Aug. 23, 1960, as amended at 27 F.R. 1010, Feb. 3, 1962]

§ 3.8 Amphetamine and methamphetamine inhalers regarded as prescription drugs.

(a) Recurring reports of abuse and misuse of methamphetamine (also known as desoxyephedrine) inhalers show that they have a potentiality for harmful effect and that they should not be freely available to the public through over-the-counter sale. From complaints by law-enforcement officials, health officials, individual physicians, parents, and others as well as from Food and Drug Administration investigations, it is evident that the wicks from these inhalers are being removed and the methamphetamine they contain is being used as a substitute for amphetamine tablets. Amphetamine tablets and amphetamine inhalers have been restricted to prescription sale because of their potentiality for harm to the user.

(b) It is the considered opinion of the Food and Drug Administration that, in order to adequately protect the public health, inhalers containing methamphetamine or methamphetamine salts (ddesoxyephedrine, or dl-desoxyephedrine, or their salts), as well as amphetamine inhalers should be restricted to prescription sale and should be labeled with the legend "Caution: Federal law prohibits dispensing without prescription."

(Secs. 503 (b) (1) (B), 52 Stat. 1052 as amended; 21 U.S.C. 353(b) (1) (B)) [30 F.R. 1845, Feb. 10, 1965]

§ 3.9

Label declaration of vitamin E in food for special dietary use.

(a) Section 125.3(a) (2) of this chapter, issued under the authority of section 403 (j) of the Federal Food, Drug, and Cosmetic Act (sec. 403(j), 52 Stat. 1048; 21 U.S.C. 343(j)) requires that if a food purports to be or is represented for special dietary use by man by reason, in whole or in part, of a vitamin for which the need in human nutrition has not been established, the label of such food shall bear the statement "The need for

in human nutrition has not been established," the blank to be filled in with the name of such vitamin.

(b) Heretofore the Food and Drug Administration has considered vitamin E as among those vitamins for which the need in human nutrition has not been established. However, in the opinion of nutrition scientists, recent evidence showed that this vitamin is needed in

human nutrition. The scientific studies upon which this conclusion is based demonstrate that the vitamin E utilized in the physiological processes of the human body is that derived only from the diet. The Food and Drug Administration therefore considers the requirement of § 125.3 (a) (2) of this chapter, quoted in paragraph (a) of this section as no longer applicable to food offered for special dietary use by reason of vitamin E.

(c) The difficulty of producing experimental dietary deficiency of vitamin E emphasizes that the diets used in this country are amply supplied with this vitamin. Any claim in the labeling of drugs or of foods offered for special dietary use by reason of vitamin E that there is need for dietary supplementation with vitamin E, will be considered false. (Sec. 403(1), 52 Stat. 1048; 21 U.S.C. 343 (1)) [24 F.R. 8792, Oct. 29, 1959; 24 F.R. 8927, Nov. 3, 1959]

§ 3.10 Notice to manufacturers and users in food products of monosodium glutamate.

In the light of information now before the Food and Drug Administration on the manner of use of monosodium glutamate in foods, this Agency is not disposed to maintain the position previously expressed by it on April 11, 1940, in a trade correspondence letter designated as TC 233 that monosodium glutamate be designated as an artificial flavoring on labels of foods to which it is added. Where it is used as an ingredient in a food for which a standard of identity has not been promulgated under the Federal Food, Drug, and Cosmetic Act, its presence should be declared on the label by its common or usual name, monosodium glutamate, in compliance with section 403 (i) (2) of the act. Since none of the standards of identity for food so far promulgated under section 401 provide for the inclusion of monosodium glutamate as an optional ingredient, this substance may not be used in such standardized foods unless and until the appropriate standards are amended after hearing. If in any case the addition of monosodium glutamate has the effect of concealing damage or inferiority, or of making the article appear to be of better or greater value than it is, the article would be classed as adulterated regardless of labeling.

[20 F.R. 9544, Dec. 20, 1955]

§ 3.11

Notice to manufacturers, packers, and distributors of estrogenic hormone preparations.

Some drug preparations fabricated wholly or in part from estradiol and labeled as to potency in terms of international units or in terms of international units of estrone activity have been marketed. The international unit of the estrus-producing hormone was established by the International Conference on the Standardization of Sex Hormones at London, England, on August 1, 1932. This unit was defined as "the specific estrus-producing activity contained in 0.1 gamma (=0.0001 mg.) of the standard" hydroxyketonic hormone found in urine (estrone). The International Conference declared that it did not recommend the determination of the activity of nonhydroxyketonic forms of estrogenic hormones in units of estrone because of the varying ratios between the activity of such nonhydroxyketonic estrogenic hormones and estrone, when measured by different methods on test animals. There is no international unit for measuring the activity of estradiol and no accepted relationship between its activity and that of estrone, either in test animals or in humans. The declaration of potency of estradiol in terms of international units or in terms of international units of estrone activity is therefore considered misleading, within the meaning of 21 U.S.C. 352(a). The declaration of the estradiol content of an estrogenic hormone preparation in terms of weight is considered appropriate. [20 F.R. 9544, Dec. 20, 1955, as amended at 22 F.R. 10685, Dec. 25, 1957]

§3.12 Tannic acid and barium enema preparations.

(a) It has become a widespread practice for tannic acid to be added to barium enemas to improve X-ray pictures. Tannic acid is capable of causing diminished liver function and severe liver necrosis when absorbed in sufficient amounts. The medical literature reports a number of deaths associated with the addition of tannic acid to barium enemas. There is a lack of scientific evidence to establish the conditions, if any, under which tannic acid is safe and effective for use in enemas. Tannic acid for rectal use to enhance X-ray visualization is regarded as a new drug within the meaning of section 201(p) of the Federal Food, Drug, and Cosmetic Act.

(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(f) (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-a m in o-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]