reasonable certainty that no harm will result from the intended use of the color additive.

(j) The term "straight color" means a color additive listed in Subparts C, D, E, F, G, and H of this part, and includes lakes and such substances as are permitted by the specifications for such color.

(k) The term "mixture" means a color additive made by mixing two or more straight colors, or one or more straight colors and one or more diluents.

(1) The term "lake” means a straight color extended on a substratum by adsorption, coprecipitation, or chemical combination that does not include any combination of ingredients made by simple mixing process.

(m) The term "diluent" means any component of a color additive mixture that is not of itself a color additive and has been intentionally mixed therein to facilitate the use of the mixture in coloring foods, drugs, or cosmetics or in coloring the human body. The diluent may serve another functional purpose in the foods, drugs, or cosmetics, as for example sweetening, flavoring, emulsifying, or stabilizing, or may be a functional component of an article intended for coloring the human body.

(n) The term "substratum" means the substance on which the pure color in a lake is extended.

(0) The term "pure color" means the color contained in a color additive, exclusive of any intermediate or other component, or of any diluent or substratum contained therein.

(p) The term "batch" means a homogeneous lot of color additive or color additive mixture produced by an identified production operation, which is set apart and held as a unit for the purpose of obtaining certification of such quantity.

(q) The term "batch number" means the number assigned to a batch by the person who requests certification thereof.

(r) The term "lot number" means an identifying number or symbol assigned to a batch by the Food and Drug Administration.

(s) The term "area of the eye" means the area enclosed within the circumference of the supra-orbital ridge and the infra-orbital ridge, including the eyebrown, the skin below the eyebrow, the eyelids and the eyelashes, and conjunctival sac of the eye, the eyeball, and the

soft areolar tissue that lies within the perimeter of the infra-orbital ridge.

(t) The term "package" means the immediate container in which a color additive or color additive mixture has been packed for shipment or delivery. If the package is then packed in a shipping carton or other protective container, such container shall not be considered to be the immediate container. In the case of color additive mixtures for household use containing less than 15 percent pure color, when two or more containers of 3 ounces each or less, each containing a different color, are distributed as a unit, the immediate container for such unit shall be considered to be the package as defined in this section.

(u) The "hair dye" exemption in section 601(a) of the act applies to those articles intended for use in altering the color of the hair and which are, or which bear or contain, color additives with the sensitization potential of causing skin irritation in certain individuals and possible blindness when used for dyeing the eyelashes or eyebrows. The exemption is permitted with the condition that the label of any such article bear conspicuously the statutory caution and adequate directions for preliminary patch-testing. If the poisonous or deleterious substance in the "hair dye" is one to which the caution is inapplicable and for which patch-testing provides no safeguard, the exemption does not apply; nor does the exemption extend to poisonous or deleterious diluents that may be introduced as wetting agents, hair conditioners, emulsifiers, or other components in a color shampoo, rinse, tint, or similar dual-purpose cosmetics that alter the color of the hair.

NOTE: By order of the Commissioner, 28 FR. 6449, June 22, 1963, a transitional period of 2 years is granted for "coaltar” hair dyes in commercial use which would not be exempt under paragraph (u) of this section.

§ 8.2 Related substances.

(a) Different color additives may cause similar or related pharmacological or biological effects, and, in the absence of evidence to the contrary, those that do so will be considered to have additive toxic effects.

(b) Food additives may also cause pharmacological or biological effects similar or related to such effects caused by color additives, and, in the absence of evidence to the contrary, those that do

so will be considered as having additive toxic effects.

(c) Pesticide chemicals may also cause pharmacological or biological effects similar or related to such effects caused by color additives, and, in the absence of evidence to the contrary, those that do so will be considered to have additive toxic effects.

(d) In establishing tolerances for color additives, the Commissioner will take into consideration, among other things, the amount of any common component permitted in other color additives, in food additives, and in pesticide chemical residues as well as the similar biological activity (such as cholinesterase inhibition) produced by such substance.

§ 8.3

or

Color additives in standardized foods, new drugs, and antibiotics. (a) Standardized foods. (1) Where a petition is received for issuance amendment of a regulation establishing a definition and standard of identity for a food under section 401 of the act, which proposes the inclusion of a color additive in the standardized food, the provisions of the regulations in this part shall apply with respect to the information that must be submitted with respect to the safety of the color additive (if such information has not previously been submitted and safety of the color additive for the intended use has not been already established), and the petition must show also that the use of the color additive in the standardized food would be in conformance with section 401 of the act or with the terms of a temporary permit issued under § 10.5 of this chapter.

(2) If a petition for a definition and standard of identity contains a proposal for a color additive regulation, and the petitioner fails to designate it as such, the Commissioner, upon determining that the petition includes a proposal for a color additive regulation, shall so notify the petitioner and shall thereafter proceed in accordance with the regulations in this part.

(3) A regulation will not be issued allowing the use of a color additive in a food for which a definition and standard of identity is established, unless its issuance is in conformance with section 401 of the act or with the terms of a temporary permit issued under § 10.5 of this chapter. When the contemplated use of such additive complies with the terms of a temporary permit, the color additive regulation will be conditioned on

such compliance and will expire with the expiration of the temporary permit.

(b) New drugs and antibiotics. (1) Where an application for a new drug or for certification of an antibiotic drug is received and this application proposes, for coloring purposes only, the inclusion of a color additive, the provisions of the regulations in this part shall apply with respect to the information that must be submitted about the safety of the color additive, if such information has not previously been submitted and safety of the color additive for the intended use has not already been established.

(2) If an application for a new drug or certification of an antibiotic drug inferentially contains a proposal for a color additive regulation, and the applicant fails to designate it as such, the Commissioner, upon determining that the application includes a proposal for a color additive regulation, shall so notify the applicant and shall thereafter proceed in accordance with the regulations in this part.

(3) Where a petition for a color additive must be filed in accordance with subparagraph (2) of this paragraph, the date of filing of the color additive petition shall be considered as the date of filing of the new-drug application or the request for certification of the antibiotic drug.

§ 8.4 Petitions proposing regulations for color additives.

(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 postoffice 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

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 on....... 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 the 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 investigations 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.

(e) The petition must be signed by the petitioner or by his attorney or authorized agent, who is a resident of the United States.

(f) The data specified under the several lettered headings should be submitted on separate sheets or sets of sheets, suitably identified. If such data have already been submitted with an earlier application, the present petition may incorporate it by specific reference to the earlier petition.

§ 8.5 Notification of filing of petition.

(a) Except where the petition involves a new drug, the Commissioner, within 15 days after receipt, will notify the petitioner of acceptance or nonacceptance of a petition, and if not accepted the reasons therefor. If accepted, the date of the notification letter sent to petitioner becomes the date of filing for the purposes of section 706(d) (1) of the act. If the petitioner desires, he may supplement a deficient petition after being notified regarding deficiencies. If the supplementary material or explanation of the petition is deemed acceptable, petitioner shall be notified. The date of such notification becomes the date of filing. If the petitioner does not wish to supplement or explain the petition and requests in writing that it be filed as submitted, the petition shall be filed and the petitioner so notified. The date of such notification becomes the date of filing. Where the petition involves a new drug or certifiable antibiotic, notification to the petitioner will be made in accordance with § 8.3(b) (3).

(b) The Commissioner will cause to be published in the FEDERAL REGISTER Within 30 days from the date of filing of such petition a notice of the filing, the name of the petitioner, and a brief description of the proposal in general terms. A copy of the notice will be mailed to the petitioner when the original document is signed.

§ 8.6 Publication of regulation.

The Commissioner will forward for publication in the FEDERAL REGISTER, within 90 days after filing of the petition (or within 180 days if the time is extended as provided for in section 706(d)(1) of the act):

(a) A regulation listing in Subpart C, D, E, F, G, or H of this part the color additive on the appropriate list or lists as provided under section 706(b) (1).

(1) Such a regulation may list the color additive for use generally in or on foods, drugs, or cosmetics or for use in coloring the human body, as the case may be, or may prescribe the conditions under which the color additive may be safely used (including, but not limited to, specifications as to the particular food, drug, or cosmetic or classes of food, drugs, or cosmetics in or on which such color additive may be used, or for the material intended for coloring the human body; the maximum quantity of any straight color or diluent that may be used or permitted to remain in or on such food, drug, or cosmetic or article intended for coloring the human body; the manner in which such color additive may be added to or used in or on such food, drug, or cosmetic or for coloring the human body; and any directions or other labeling or packaging requirements for such color additives deemed necessary to assure the safety of such use).

(2) Such regulations shall list the color additive only for the use or uses for which it has been found suitable and for which it may safely be employed. Alternatively, the Commissioner shall by order deny the petition, and notify the petitioner of such order and the reasons therefor.

(b) Whenever the Commissioner finds that batch certification is not necessary for the protection of the public health he will, by order, exempt the color additive from the certification procedure. In determining whether certification of a color additive is necessary, the Commissioner will consider the composition of

the additive, its manufacturing process, possible impurities, its toxic potential, control and analytical procedures necessary to assure compliance with the listing specifications, and the variability of its composition.

§ 8.7 Samples.

The Commissioner may request samples of the color additive, articles used as components thereof, or of the food, drug, or cosmetic in which the color additive is proposed to be used, or which comprises the color additive, and any additional information needed to clarify a submitted method at any time while a petition is under consideration. The Commissioner shall specify in the request for a sample of the color additive, or articles used as components thereof, or of the food, drug, or cosmetic in which the color additive is proposed to be used, or which comprises the color additive, a quantity deemed adequate to permit tests of analytical methods to determine quantities of the color additive present in products for which it is intended to be used or adequate for any study or investigation reasonably required with respect to the safety of the color additive or the physical or technical effect it produces. The date used for computing the 90-day limit for the purposes of section 706(d)(1) of the act shall be moved forward 1 day for each day, after mailing date of the request, taken by the petitioner to submit the information and sample. If the information or sample is requested a reasonable time in advance of the 180 days, but is not submitted within such 180 days after filing of the petition, the petition will be considered withdrawn without prejudice.

§ 8.8

Extension of time for studying petitions; substantive amendments; withdrawal of petitions without prejudice.

(a) Extension of time for studying petitions. If the Commissioner determines that additional time is needed to study and investigate the petition, he shall by written notice to the petitioner extend the 90-day period for not more than 180 days after the filing of the petition.

(b) Substantive amendments. After a petition has been filed, the petitioner may submit additional information or data in support thereof. In such cases, if the Commissioner determines that the