record thereof they will be transmitted to the Treasurer of the United States for deposit in the special account "Salaries and Expenses, Certification, Inspection, and Other Services, Food and Drug Administration."

(q) The Commissioner of Food and Drugs may waive or refund such fees in whole or in part when in his judgment such action will promote the public interest.

(r) Any person who believes that payment of these fees will work a hardship on him may petition the Commissioner of Food and Drugs to waive or refund the fees.

Subpart B-Packaging and Labeling 870.20 Packaging requirements for straight colors (other than hair dyes). Straight colors shall be packaged in containers which prevent changes in composition. Packages shall be sealed so that they cannot be opened without breaking the seal. An unavoidable change in moisture content caused by the ordinary and customary exposure that occurs in good storage, packing, and distribution practice is not considered a change in composition. If the packaging material is a food additive it shall be authorized by an appropriate regulation in Parts 170 through 189 of this chapter.

870.25 Labeling requirements for color additives (other than hair dyes).

(a) General labeling requirements. All color additives shall be labeled with sufficient information to assure their safe use and to allow a determination of compliance with any limitations imposed by this part and Parts 71, 73, 74, 80, and 81 of this chapter. In addition to all other information required by the act, labels for color additives, except those in a form suitable for coloring the human body, shall state:

(1) The name of the straight color or the name of each ingredient comprising the color additive, if it is a mixture.

(2) A statement indicating general limitations for the use of the color additive, such as "for food use only"; "for food, drug, and cosmetic use";

"for use in drugs for external application only."

(3) Where regulations issued impose quantitative limitations for a general or specific use of a straight color, the amount of each such straight color in terms of weight per unit/volume or percent by weight.

(4) An expiration date if stability data require it.

(b) Special labeling for color additives with tolerances. Where tolerances are imposed for a general or specific use of a color additive, the label shall in addition provide directions for use of the color additive which if followed will preclude the food, drug, or cosmetic to which it is added from containing an amount of the color additive in excess of the tolerance.

(c) Special labeling for color additives with other limitations. If use of the color additive is subject to other limitations prescribed in this part, such limitations shall be stated on the label of the color additive by a plain and conspicuous statement. Examples of such limitation statements are: "Do not use in products used in the area of the eye"; "Do not use for coloring drugs for injection."

(d) Special labeling for color additives not exempt from certification. Color additives not exempt from the certification procedures shall in addition include in the labeling the lot number assigned by the Color Certification Branch, except that in the case of any mixture for household use which contains not more than 15 percent of pure color and which is in packages containing not more than 3 ounces there appears on the label, a code number which the manufacturer has identified with the lot number by giving to the Food and Drug Administration written notice that such code number will be used in lieu of the lot number.

Subpart C-Safety Evaluation

§ 70.40 Safety factors to be considered.

In accordance with section 706(b)(5)(A)(iii) of the act, the following safety factor will be applied in determining whether the proposed use of a color additive will be safe: Except

where evidence is submitted which justifies use of a different safety factor, a safety factor of 100 to 1 will be used in applying animal experimentation data to man; that is, a color additive for use by man will not be granted a tolerance that will exceed 1/100th of the maximum no-effect level for the most susceptible experimental animals tested. The various species of experimental animals used in the tests shall conform to good pharmacological practice.

870.42 Criteria for evaluating the safety of color additives.

(a) In deciding whether a petition is complete and suitable for filing and in reaching a decision on any petition filed, the Commissioner will apply the "safe-for-use" principle. This will require the presentation of all needed scientific data in support of a proposed listing to assure that each listed color additive will be safe for its intended use or uses in or on food, drugs, or cosmetics. The Commissioner may list a color additive for use generally in or on food, in or on drugs, or in or on cosmetics when he finds from the data presented that such additive is suitable and may safely be employed for such general use; he may list an additive only for more limited use or uses for which it is proven suitable and may safely be employed; and he is authorized to prescribe broadly the conditions under which the additive may be safely employed for such use or uses. This may allow the use of a particular dye, pigment, or other substance with certain diluents, but not with others, or at a higher concentration with some than with others.

(b) The safety for external color additives will normally be determined by tests for acute oral toxicity, primary irritation, sensitization, subacute dermal toxicity on intact and abraded skin, and carcinogenicity by skin application. The Commissioner may waive any of such tests if data before him otherwise establish that such test is not required to determine safety for the use proposed.

(c) Upon written request describing the proposed use of a color additive and the proposed experiments to determine its safety, the Commissioner

will advise a person who wishes to establish the safety of a color additive whether he believes the experiments planned will yield data adequate for an evaluation of the safety of the additive.

870.45 Allocation of color additives.

Whenever, in the consideration of a petition or a proposal to list a color additive or to alter an existing listing, the data before the Commissioner fail to show that it would be safe to list the color additive for all the uses proposed or at the levels proposed, the Commissioner will notify the petitioner and other interested persons by publication in the FEDERAL REGISTER that it is necessary to allocate the safe tolerance for the straight color in the color additive among the competing needs. This notice shall call for the presentation of data by all interested persons on which the allocation can be made in accordance with section 706(b)(8) of the act. The time for acting upon the petition shall be stayed until such data are presented, whereupon the time limits shall begin to run anew. As promptly as possible after presentation of the data, the Commissioner will, by order, announce the allocation and the tolerance limitations.

8 70.50 Application of the cancer clause of section 706 of the act.

(a) Color additives that may be ingested. Whenever (1) the scientific data before the Commissioner (either the reports from the scientific literature or the results of biological testing) suggest the possibility that the color additive including its components or impurities has induced cancer when ingested by man or animal; or (2) tests which are appropriate for the evaluation of the safety of additives in food suggest that the color additive, including its components or impurities, induces cancer in man or animal, the Commissioner shall determine whether, based on the judgment of appropriately qualified scientists, cancer has been induced and whether the color additive, including its components or impurities, was the causative substance. If it is his judgment that

the data do not establish these facts, the cancer clause is not applicable; and if the data considered as a whole establish that the color additive will be safe under the conditions that can be specified in the applicable regulation, it may be listed for such use. But if in the judgment of the Commissioner, based on information from qualified scientists, cancer has been induced, no regulation may issue which permits its use.

(b) Color additives that will not be ingested. Whenever the scientific data before the Commissioner suggest the possibility that the color additive, including its components or impurities, has induced cancer in man or animals by routes other than ingestion, the Commissioner shall determine whether, based on the judgment of appropriately qualified scientists, the test suggesting the possibility of carcinogenesis is appropriate for the evaluation of the color additive for a use which does not involve ingestion, cancer has been induced, and the color additive, including its components or impurities, was the causative substance. If it is his judgment that the data do not establish these facts, the cancer clause is not applicable to preclude external drug and cosmetic uses, and if the data as a whole establish that the color additive will be safe under conditions that can be specified in the regulations, it may be listed for such use. But if, in the judgment of the Commissioner, based on information from qualified scientists, the test is an appropriate one for the consideration of safety for the proposed external use, and cancer has been induced by the color additive, including its components or impurities, no regulation may issue which permits its use in external drugs and cosmetics.

(c) Color additives for use as an ingredient of feed for animals that are raised for food production. Color additives that are an ingredient of the feed for animals raised for food production and that have the potential to contaminate human food with residues whose consumption could present a risk of cancer to people must satisfy the requirements of Subpart E of Part 500 of this chapter.

(Secs. 402, 403, 409, 512, 701(a), 706, 52 Stat. 1046-1048 as amended, 1055, 72 Stat. 17851788 as amended, 74 Stat. 399-403, 82 Stat. 343-351 (21 U.S.C. 342, 343, 348, 360b, 371(a), 376))

[42 FR 15636, Mar. 22, 1977, as amended at 43 FR 22675, May 26, 1978; 52 FR 49586, Dec. 31, 1987]

§ 70.51 Advisory committee on the applicability of the anticancer clause.

All requests for and procedures governing any advisory committee on the anticancer clause shall be subject to the provisions of Part 14 of this chapter, and particularly Subpart H of that part.

§ 70.55 Request for scientific studies.

The Commissioner will consider requests by any interested person who desires the Food and Drug Administration to conduct scientific studies to support a petition for a regulation for a color additive. If favorably acted upon, such studies will be limited to pharmacological investigations, studies of the chemical and physical structure of the color additive, and methods of analysis of the pure color additive (including impurities) and its identification and determination in foods, drugs, or cosmetics, as the case may be. All requests for such studies shall be accompanied by the fee prescribed in § 70.19.

(a) Any interested person may propose the listing of a color additive for use in or on any food, drug, or cosmetic or for coloring the human body. Such proposal shall be made in a petition in the form prescribed in paragraph (c) of this section. The petition shall be submitted in triplicate. If any part of the material submitted is in a foreign language, it shall be accompanied by an accurate and complete English translation. The petitioner shall state the post-office address in the United States to which published notices or orders issued or objections filed pursuant to section 706 of the act may be sent.

(b) Pertinent information may be incorporated in, and will be considered as part of, a petition on the basis of specific reference to such information submitted to and retained in the files of the Food and Drug Administration. However, any reference to unpublished information furnished by a person other than the applicant will not be considered unless use of such information is authorized in a written statement signed by the person who submitted the information. Any reference to published information offered in support of a color additive petition should be accompanied by reprints or photostatic copies of such references.

on

Petitioner submits this pursuant to section 706(b)(1) of the Federal Food, Drug, and Cosmetic Act requesting listing by the Commissioner of the color additive -as suitable and safe for use in or -subject to the conditions that [Petitioner may propose a listing for general use in food, drugs, or cosmetics or, if such general listing is not believed suitable and safe, the petitioner shall describe the conditions under which he believes the additive can be safely used and for which it will be suitable. These conditions may include tolerance limitations, specifications as to the manner in which the additive may be added or used, and directions and other labeling or packaging safeguards that should be applied. The level of use proposed should not be higher than reasonably required to accomplish the intended color effect.]

Attached hereto in triplicate and constituting a part of this petition are the following:

A. The name and all pertinent information concerning the color additive, including chemical identity and composition of the color additive, its physical, chemical, and biological properties, and specifications prescribing its component(s) and identifying and limiting the reaction byproducts and other impurities.

The petition shall contain a description of the chemical and physical tests relied upon to identify the color additive and shall contain a full description of the methods used in, and the facilities and controls used for, the production of the color additive. These shall establish that it is a substance of reproducible composition. Alternative methods and controls and variations in methods and controls, within reasonable limits, that do not affect the characteristics of the substance or the reliability of the controls may be specified.

The petition shall supply a list of all substances used in the synthesis, extraction, or other method of preparation of any straight color, regardless of whether they undergo

chemical change in the process. Each substance should be identified by its common or usual name and its complete chemical name, using structural formulas when necessary for specific identification. If any proprietary preparation is used as a component, the proprietary name should be followed by a complete quantitive statement of composition. Reasonable alternatives for any listed substance may be specified.

If the petitioner does not himself perform all the manufacturing, processing, and packing operations for a color additive, the petitioner shall identify each person who will perform a part of such operations and designate the part.

The petition shall include stability data, and, if the data indicate that it is needed to insure the identity, strength, quality, or purity of the color additive, the expiration period that will be employed as well as any packaging and labeling precautions needed to preserve stability.

B. The amount of the color additive proposed for use and the color effect intended to be achieved, together with all directions, recommendations, and suggestions regarding the proposed use, as well as specimens of the labeling proposed for the color additive. If the color effect results or may reasonably be expected to result from use of the color additive in packaging material, the petitioner shall show how this may occur and what residues may reasonably be anticipated.

Typewritten or other draft-labeling copy will be accepted for consideration of the petition provided final printed labeling identical in content to the draft copy is submitted as soon as available, and prior to the marketing of the color additive. The printed labeling shall conform in prominence and conspicuousness with the requirements of the

act.

If the color additive is one for which a tolerance limitation is required to assure its safety, the level of use proposed should be no higher than the amount reasonably required to accomplish the intended physical or other technical effect, even though the safety data may support a higher tolerance. If the safety data will not support the use of the amount of the color additive reasonably needed to accomplish the desired color effect, the requested tolerance will not be established. Petitioners are expected to propose the use of color additives in accordance with sound color chemistry.

C.1. A description of practicable methods to determine the pure color and all intermediates, subsidiary colors, and other components of the color additive.

2. A description of practicable methods to determine the amount of the color additive in any raw, processed, and/or finished food, drug, or cosmetic in which use of the color additive is proposed. (The tests proposed shall be those that can be used for food,

drug, or cosmetic control purposes and can be applied with consistent results by any properly equipped laboratory and trained personnel.)

3. A description of methods for identification and determination of any substance formed in or on such food, drug, or cosmetic because of the use of the color additive. (If it is the petitioner's view that any such method would not be needed, under the terms of section 706(b)(5)(A)(iv), a statement shall be submitted in lieu of methods as to the basis for such view.)

D. Full reports of investigation made with respect to the safety of the color additive.

(A petition will be regarded as incomplete unless it includes full reports of adequate tests reasonably applicable to show whether or not the color additive will be safe for its intended use. The reports ordinarily should include detailed data derived from appropriate animal and other biological experiments in which the methods used and the results obtained are clearly set forth. The petition shall not omit without explanation any data that would influence the evaluation of the safety of the color additive).

E. Complete data which will allow the Commissioner to consider, among other things, the probable consumption of, and/or other relevant exposure from the additive and of any substance formed in or on food, drugs, or cosmetics because of such additive; and the cumulative effect, if any, of such additive in the diet of man or animals, taking into account the same or any chemically or pharmacologically related substance or substances in the diet including, but not limited to food additives and pesticide chemicals for which tolerances or exemptions from tolerances have been established. F. Proposed tolerances and other limitations on the use of the color additive, if tolerances and limitations are required in order to insure its safety. A petitioner may include a proposed regulation.

G. If exemption from batch certification is requested, the reasons why it is believed such certification is not necessary (including supporting data to establish the safety of the intended use).

H. If submitting a petition to alter an existing regulation issued pursuant to section 706(b) of the act, full information on each proposed change that is to be made in the original regulation must be submitted. The petition may omit statements made in the original petition concerning which no change is proposed. A supplemental petition must be submitted for any change beyond the variations provided for in the original petition and the regulation issued on the basis of the original petition.

I. The prescribed fee of $ for admitting the color additive to listing is enclosed