the method used to analyze for the substance.

(5) The results of an analysis of existing toxicological information on the substance and its impurities. This information on the substance is needed to show whether an animal carcinogen bioassay has been carried out, or whether there is some other basis for suspecting that the substance is a carcinogen or potent toxin. This type of information on the impurities is needed to show whether any of them are carcinogenic, and, if carcinogenic, whether their TD50 values are greater than 6.25 milligrams per kilogram bodyweight per day in accordance with paragraph (a)(1) of this section.

(6) Information on the environmental impact that would result from the proposed use of the substance. The request should contain either a claim for categorical exclusion as specified in § 25.32 of this chapter or an environmental assessment as specified in §25.40 of this chapter.

(d) Data to be reviewed under this section shall be submitted to the Food and Drug Administration's Office of Premarket Approval (HFS-200), 5100 Paint Branch Pkwy., College Park, MD 20740.

(e) The Food and Drug Administration will inform the requestor by letter whether the specific food-contact application is exempt from regulation as a food additive or not. Although a substance that migrates to food at a level that results in a dietary concentration at or below the threshold of regulation will not be the subject of a regulation published in the FEDERAL REGISTER and will not appear in the Code of Federal Regulations, the Food and Drug Administration will maintain a list of substances exempted from regulation as food additives under this section on display at the Dockets Management Branch. This list will include the name of the company that made the request, the chemical name of the substance, the specific use for which it has received an exemption from regulation as a food additive, and any appropriate limitations on its use. The list will not include any trade names. This list will enable interested persons to see the types of uses of food-contact materials being exempted under the regulation.

Interested persons may also obtain a copy of the list of exempted substances by contacting the Food and Drug Administration's Office of Premarket Approval (HFS-200), 5100 Paint Branch Pkwy., College Park, MD 20740. For actions requiring an environmental assessment, the agency's finding of no significant impact and the evidence supporting that finding, contained in the petitioner's environmental assessment, also will be available for public inspection at the Dockets Management Branch in accordance with §25.51(b)(2) of this chapter. Requests for copies of releasable information contained in submissions requesting exemptions from the food additive regulations will be handled in accordance with the Food and Drug Administration's Freedom of Information Act procedures, as described in part 20 of this chapter. In particular, data and information that fall within the definitions of a trade secret or confidential commercial or financial information are not available for public disclosure in accordance with §20.61(c) of this chapter.

(f) If the request for an exemption from regulation as a food additive is not granted, the requestor may submit a petition to the Food and Drug Administration for reconsideration of the decision in accordance with the provisions of § 10.33 of this chapter.

(g) If the Food and Drug Administration receives significant new information that raises questions about the dietary concentration or the safety of a substance that the agency has exempted from regulation, the Food and Drug Administration may reevaluate the substance. If the Food and Drug Administration tentatively concludes that the information that is available about the substance no longer supports an exemption for the use of the foodcontact material from the food additive regulations, the agency will notify any persons that requested an exemption for the substance of its tentative decision. The requestors will be given an opportunity to show why the use of the substance should not be regulated under the food additive provisions of the act. If the requestors fail to adequately respond to the new evidence, the agency will notify them that further use of the substance in question

for the particular use will require a food additive regulation. This notification will be placed on public display at the Dockets Management Branch as part of the file of uses of substances exempted from regulation as food additives. The Food and Drug Administration recognizes that manufacturers other than those that actually made a request for exemption may also be using exempted substances in food-contact articles under conditions of use (e.g., use levels, temperature, type of food contacted, etc.) that are similar to those for which the exemption was issued. Because only requestors will be notified as part of the revocation process described in this section, the Food and Drug Administration plans to notify other manufacturers by means of a notice published in the FEDERAL REGISTER of its decision to revoke an exemption issued for a specific use of a substance in a food contact article.

(h) Guidance documents to assist requestors in the preparation of submissions seeking exemptions from the food additive regulations are available from the Food and Drug Administration's Office of Premarket Approval (HFS200), 5100 Paint Branch Pkwy., College Park, MD 20740. Interested persons are encouraged to obtain specific guidance from the Food and Drug Administration on the appropriate protocols to be used for obtaining migration data, on the validation of the analytical methods used to quantify migration levels, on the procedures used to relate migration data to dietary exposures, and on any other issue not specifically covered in the Food and Drug Administration's guidance documents.

[60 FR 36595, July 17, 1995, as amended at 62 FR 40599, July 29, 1997; 65 FR 56479, Sept. 19, 2000]

sulting from the fluoridation of bottled water within the limitation established in § 103.35(d) of this chapter, and (c) to that authorized by regulations (40 CFR part 180) under section 408 of the Act.

§ 170.50 Glycine (aminoacetic acid) in food for human consumption.

(a) Heretofore, the Food and Drug Administration has expressed the opinion in trade correspondence that glycine is generally recognized as safe for certain technical effects in human food when used in accordance with good manufacturing practice; however:

(1) Reports in scientific literature indicate that adverse effects were found in cases where high levels of glycine were administered in diets of experimental animals.

(2) Current usage information indicates that the daily dietary intake of glycine by humans may be substantially increasing due to changing use patterns in food technology.

Therefore, the Food and Drug Administration no longer regards glycine and its salts as generally recognized as safe for use in human food and all outstanding letters expressing sanction for such use are rescinded.

(b) The Commissioner of Food and Drugs concludes that by May 8, 1971,

manufacturers:

(1) Shall reformulate food products for human use to eliminate added glycine and its salts; or

(2) Shall bring such products into compliance with an authorizing food additive regulation. A food additive petition supported by toxicity data is required to show that any proposed level of glycine or its salts added to foods for human consumption will be safe.

(c) The status of glycine as generally recognized as safe for use in animal feed, as prescribed in §582.5049 of this chapter, remains unchanged because the additive is considered an essential nutrient in certain animal feeds and is safe for such use under conditions of good feeding practice.

§ 170.60 Nitrites and/or nitrates in curing premixes.

(a) Nitrites and/or nitrates are food additives when combined in curing premixes with spices and/or other flavoring or seasoning ingredients that

contain or constitute a source of secondary or tertiary amines, including but not limited to essential oils, disodium inosinate, disodium guanylate, hydrolysates of animal or plant origin (such as hydrolyzed vegetable protein), oleoresins of spices, soy products, and spice extractives. Such food additives may be used only after the establishment of an authorizing food additive regulation. A food additive petition submitted pursuant to §§ 171.1 and 171.100 of this chapter, supported by data demonstrating that nitrosamines are not formed in curing premixes containing such food additives, is required to establish safety.

(b) Nitrites and/or nitrates, when packaged separately from flavoring and seasoning in curing premixes, may continue to be used under prior sanctions in the commercial curing of meat and meat products and poultry products and in accordance with the provisions of §§ 172.170 and 172.175 of this chapter that apply to meat curing preparations for the home curing of meat and meat products, including poultry and wild game. To assure safe use of such ingredients the labeling of the premixes shall bear instructions to the user that such separately packaged ingredients are not to be combined until just prior to use. Encapsulating or coating some or all of the ingredients does not constitute separate packaging.

(a) Petitions to be filed with the Commissioner under the provisions of section 409(b) of the Federal Food, Drug, and Cosmetic Act (the act) shall be submitted in triplicate (quadruplicate, if intended uses include use in meat, meat food product, or poultry product). If any part of the material submitted is in a foreign language, it shall be accompanied by an accurate and complete English translation. The petition shall state petitioner's post office address to which published notices or orders issued or objections filed pursuant to section 409 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 it. Any reference to published information offered in support of a food additive petition should be accompanied by reprints or photostatic copies of such references.

(c) Petitions shall include the following data and be submitted in the following form:

Attached hereto, in triplicate (quadruplicate, if intended uses include use in meat, meat food product, or poultry product), and constituting a part of this petition are the following:

A. The name and all pertinent information concerning the food additive, including chemical identity and composition of the food additive, its physical, chemical, and biological properties, and specifications prescribing the minimum content of the desired component(s) and identifying and limiting the reaction byproducts and other impurities. Where such information is not available, a statement as to the reasons why it is not should be submitted.

When the chemical identity and composition of the food additive is not known, the petition shall contain information in sufficient detail to permit evaluation regarding the method of manufacture and the analytical controls used during the various stages of manufacturing, processing, or packing of the food additive which are relied upon to 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.

If the food additive is a mixture of chemicals, the petition shall supply a list of all substances used in the synthesis, extraction, or other method of preparation, regardless of whether they undergo chemical change in the process. Each substance should be identified by its common English name and 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 quantitative 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 food additive, the petition 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 additive, the expiration date that will be employed.

B. The amount of the food additive proposed for use and the purposes for which it is proposed, together with all directions, recommendations, and suggestions regarding the proposed use, as well as specimens of the labeling proposed for the food additive and any labeling that will be required by applicable provisions of the Federal Food, Drug, and Cosmetic Act on the finished food by reason of the use of the food additive. If the additive results or may reasonably be expected to re

sult from the use of 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 a statement is made that final printed labeling identical in content to the draft copy will be submitted as soon as available and prior to the marketing of the food additive.)

(If the food 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.)

C. Data establishing that the food additive will have the intended physical or other technical effect or that it may reasonably be expected to become a component, or to affect the characteristics, directly or indirectly, of food and the amount necessary to accomplish this. These data should include information in sufficient detail to permit evaluation with control data.

D. A description of practicable methods to determine the amount of the food additive in the raw, processed, and/or finished food and of any substance formed in or on such food because of its use. The test proposed shall be one that can be used for food-control purposes and that can be applied with consistent results by any properly equipped and trained laboratory personnel.

E. Full reports of investigations made with respect to the safety of the food additive.

(A petition may be regarded as incomplete unless it includes full reports of adequate tests reasonably applicable to show whether or not the food 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 reports of investigations that would bias an evaluation of the safety of the food additive.)

F. Proposed tolerances for the food additive, if tolerances are required in order to insure its safety. A petitioner may include a proposed regulation.

G. If submitting petition to modify an existing regulation issued pursuant to section 409(c)(1)(A) 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.

H. The petitioner is required to submit either a claim for categorical exclusion under $25.30 or 25.32 of this chapter or an environmental assessment under §25.40 of this chapter.

Yours very truly, Petitioner

By

(Indicate authority)

(d) The petitioner will be notified of the date on which his petition is filed; and an incomplete petition, or one that has not been submitted in triplicate, will usually be retained but not filed as a petition under section 409 of the Act. The petitioner will be notified in what respects his petition is incomplete.

(e) The petition must be signed by the petitioner or by his attorney or agent, or (if a corporation) by an authorized official.

(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. If part of the data have been submitted by the manufacturer of the food additive as a master file, the petitioner may refer to the master file if and to the extent he obtains the manufacturer's written permission to do so. The manufacturer may authorize specific reference to the data without disclosure to the petitioner. Nothing herein shall prevent reference to published data.

(g) A petition shall be retained but shall not be filed if any of the data prescribed by section 409(b) of the Act are lacking or are not set forth so as to be readily understood.

(h)(1) The following data and information in a food additive petition are available for public disclosure, unless extraordinary circumstances

are

shown, after the notice of filing of the petition is published in the FEDERAL REGISTER or, if the petition is not promptly filed because of deficiencies in it, after the petitioner is informed that it will not be filed because of the deficiencies involved:

(i) All safety and functionality data and information submitted with or incorporated by reference in the petition.

(ii) A protocol for a test or study, unless it is shown to fall within the exemption established for trade secrets and confidential commercial information in §20.61 of this chapter.

(iii) Adverse reaction reports, product experience reports, consumer complaints, and other similar data and information, after deletion of:

(a) Names and any information that would identify the person using the product.

(b) Names and any information that would identify any third party involved with the report, such as a physician or hospital or other institution.

(iv) A list of all ingredients contained in a food additive, whether or not it is in descending order of predominance. A particular ingredient or group of ingredients shall be deleted from any such list prior to public disclosure if it is shown to fall within the exemption established in § 20.61 of this chapter, and a notation shall be made that any such ingredient list is incomplete.

(v) An assay method or other analytical method, unless it serves no regulatory or compliance purpose and is shown to fall within the exemption established in § 20.61 of this chapter.

(2) The following data and information in a food additive petition are not available for public disclosure unless they have been previously disclosed to the public as defined in § 20.81 of this chapter or they relate to a product or ingredient that has been abandoned and they no longer represent a trade secret or confidential commercial or financial information as defined in § 20.61 of this chapter:

(i) Manufacturing methods or processes, including quality control procedures.

(ii) Production, sales, distribution, and similar data and information, except that any compilation of such data and information aggregated and prepared in a way that does not reveal data or information which is not available for public disclosure under this provision is available for public disclo

sure.

(iii) Quantitative or semiquantitative formulas.

(3) All correspondence and written summaries of oral discussions relating

197-064 D-2