[Code of Federal Regulations]
[Title 21, Volume 3]
[Revised as of April 1, 2003]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR180]
 
[Page 445]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                          SERVICES (CONTINUED)
 
PART 180--FOOD ADDITIVES PERMITTED IN FOOD OR IN CONTACT WITH FOOD ON AN INTERIM BASIS PENDING ADDITIONAL STUDY--Table of Contents
 
 
                      Subpart A--General Provisions
 
Sec.
180.1  General.
 
       Subpart B--Specific Requirements for Certain Food Additives
 
180.22  Acrylonitrile copolymers.
180.25  Mannitol.
180.30  Brominated vegetable oil.
180.37  Saccharin, ammonium saccharin, calcium saccharin, and sodium 
          saccharin.
 
    Authority: 21 U.S.C. 321, 342, 343, 348, 371; 42 U.S.C. 241.
 
    Editorial Note: Nomenclature changes to part 180 appear at 61 FR 
14482, Apr. 2, 1996, and 66 FR 56035, Nov. 6, 2001.
 
 
 
 
 
[Code of Federal Regulations]
[Title 21, Volume 3]
[Revised as of April 1, 2003]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR180.1]
 
[Page 445-446]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                          SERVICES (CONTINUED)
 
PART 180--FOOD ADDITIVES PERMITTED IN FOOD OR IN CONTACT WITH FOOD ON AN INTERIM BASIS PENDING ADDITIONAL STUDY--Table of Contents
 
                      Subpart A--General Provisions
 
Sec. 180.1  General.
 
 
    (a) Substances having a history of use in food for human consumption 
or in food contact surfaces may at any time have their safety or 
functionality brought into question by new information that in itself is 
not conclusive. An interim food additive regulation for the use of any 
such substance may be promulgated in this subpart when new information 
raises a substantial question about the safety or functionality of the 
substance but there is a reasonable certainty that the substance is not 
harmful and that no harm to the public health will result from the 
continued use of the substance for a limited period of time while the 
question raised is being resolved by further study.
    (b) No interim food additive regulation may be promulgated if the 
new information is conclusive with respect to the question raised or if 
there is a reasonable likelihood that the substance is harmful or that 
continued use of the substance will result in harm to the public health.
    (c) The Commissioner, on his own initiative or on the petition of 
any interested person, pursuant to part 10 of this chapter, may propose 
an interim food additive regulation. A final order promulgating an 
interim food additive regulation shall provide that continued use of the 
substance in food is subject to each of the following conditions:
    (1) Use of the substance in food or food contact surfaces must 
comply with whatever limitations the Commissioner deems to be 
appropriate under the circumstances.
    (2) Within 60 days following the effective date of the regulation, 
an interested person shall satisfy the Commissioner in writing that 
studies adequate and appropriate to resolve the questions raised about 
the substance have been undertaken, or the Food and Drug Administration 
may undertake the studies. The Commissioner may extend this 60-day 
period if necessary to review and act on proposed protocols. If no such 
commitment is made, or adequate and appropriate studies are not
 
[[Page 446]]
 
undertaken, an order shall immediately be published in the Federal 
Register revoking the interim food additive regulation effective upon 
publication.
    (3) A progress report shall be filed on the studies every January 1 
and July 1 until completion. If the progress report is inadequate or if 
the Commissioner concludes that the studies are not being pursued 
promptly and diligently or if interim results indicate a reasonable 
likelihood that a health hazard exists, an order will promptly be 
published in the Federal Register revoking the interim food additive 
regulation effective upon publication.
    (4) If nonclinical laboratory studies are involved, studies filed 
with the Commissioner shall include, with respect to each study, either 
a statement that the study has been or will be conducted in compliance 
with the good laboratory practice regulations as set forth in part 58 of 
this chapter, or, if any such study was not conducted in compliance with 
such regulations, a brief statement of the reason for the noncompliance.
    (5) [Reserved]
    (6) If clinical investigations involving human subjects are 
involved, such investigations filed with the Commissioner shall include, 
with respect to each investigation, a statement that the investigation 
either was conducted in compliance with the requirements for 
institutional review set forth in part 56 of this chapter, or was not 
subject to such requirements in accordance with Secs. 56.104 or 56.105, 
and that it has been or will be conducted in compliance with the 
requirements for informed consent set forth in part 50 of this chapter.
    (d) Promptly upon completion of the studies undertaken on the 
substance, the Commissioner will review all available data, will 
terminate the interim food additive regulation, and will either issue a 
food additive regulation or will require elimination of the substance 
from the food supply.
    (e) The Commissioner may consult with advisory committees, 
professional organizations, or other experts in the field, in 
evaluating:
    (1) Whether an interim food additive regulation is justified,
    (2) The type of studies necessary and appropriate to resolve 
questions raised about a substance,
    (3) Whether interim results indicate the reasonable likelihood that 
a health hazard exists, or
    (4) Whether the data available at the conclusion of those studies 
justify a food additive regulation.
    (f) Where appropriate, an emergency action level may be issued for a 
substance subject to paragraph (a) of this section that is not an 
approved food additive, pending the issuance of a final interim food 
additive regulation. Such an action level shall be issued pursuant to 
sections 306 and 402(a) of the act to identify, based upon available 
data, a safe level of use for the substance. Such an action level shall 
be issued in a notice published in the Federal Register and shall be 
followed as soon as practicable by a proposed interim food additive 
regulation. Where the available data do not permit establishing an 
action level for the safe use of a substance, use of the substance may 
be prohibited. The identification of a prohibited substance may be made 
in part 189 of this chapter when appropriate.
 
[42 FR 14636, Mar. 15, 1977, as amended at 42 FR 15674, Mar. 22, 1977; 
42 FR 52821, Sept. 30, 1977; 46 FR 8952, Jan. 27, 1981; 46 FR 14340, 
Feb. 27, 1981; 50 FR 7492, Feb. 22, 1985; 54 FR 39634, Sept. 27, 1989]
 
 
 
 
 
[Code of Federal Regulations]
[Title 21, Volume 3]
[Revised as of April 1, 2003]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR180.22]
 
[Page 446-448]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                          SERVICES (CONTINUED)
 
PART 180--FOOD ADDITIVES PERMITTED IN FOOD OR IN CONTACT WITH FOOD ON AN INTERIM BASIS PENDING ADDITIONAL STUDY--Table of Contents
 
       Subpart B--Specific Requirements for Certain Food Additives
 
Sec. 180.22  Acrylonitrile copolymers.
 
 
    Acrylonitrile copolymers may be safely used on an interim basis as 
articles or components of articles intended for use in contact with 
food, in accordance with the following prescribed conditions:
    (a) Limitations for acrylonitrile monomer extraction for finished 
food-contact articles, determined by a method of analysis titled "Gas-
Solid Chromatographic Procedure for Determining Acrylonitrile Monomer in 
Acrylonitrile-Containing Polymers and Food Simulating Solvents," which 
is incorporated by reference. Copies are available from the Center for 
Food Safety and Applied Nutrition (HFS-200), Food and Drug 
Administration, 5100 Paint Branch Pkwy., College Park,
 
[[Page 447]]
 
MD 20740, or available for inspection at the Office of the Federal 
Register, 800 North Capitol Street, NW., suite 700, Washington, DC 
20408, are as follows:
    (1) In the case of single-use articles having a volume to surface 
ratio of 10 milliliters or more per square inch of food contact surface-
-0.003 milligram/square inch when extracted to equilibrium at 120  deg.F 
with food-simulating solvents appropriate to the intended conditions of 
use.
    (2) In the case of single-use articles having a volume to surface 
ratio of less than 10 milliliters per square inch of food contact 
surface--0.3 part per million calculated on the basis of the volume of 
the container when extracted to equilibrium at 120  deg.F with food-
simulating solvents appropriate to the intended conditions of use.
    (3) In the case of repeated-use articles--0.003 milligram/square 
inch when extracted at a time equivalent to initial batch usage 
utilizing food-simulating solvents and temperatures appropriate to the 
intended conditions of use.
 
The food-simulating solvents shall include, where applicable, distilled 
water, 8 percent or 50 percent ethanol, 3 percent acetic acid, and 
either n-heptane or an appropriate oil or fat.
    (b) Where necessary, current regulations permitting the use of 
acrylonitrile copolymers shall be revised to specify limitations on 
acrylonitrile/mercaptan complexes utilized in the production of 
acrylonitrile copolymers. Such copolymers, if they contain reversible 
acrylonitrile/mercaptan complexes and are used in other than repeated-
use conditions, shall be tested to determine the identity of the complex 
and the level of the complex present in the food-contact article. Such 
testing shall include determination of the rate of decomposition of the 
complex at temperatures of 100  deg.F, 160  deg.F, and 212  deg.F using 
3 percent acetic acid as the hydrolic agent. Acrylonitrile monomer 
levels, acrylonitrile/mercaptan complex levels, acrylonitrile oligomer 
levels, descriptions of the analytical methods used to determine the 
complex and the acrylonitrile migration, and validation studies of these 
analytical methods shall be submitted by June 9, 1977, to the Center for 
Food Safety and Applied Nutrition (HFS-200), Food and Drug 
Administration, 5100 Paint Branch Pkwy., College Park, MD 20740, unless 
an extension is granted by the Food and Drug Administration for good 
cause shown. Analytical methods for the determination of acrylonitrile 
complexes with n-dodecyl-mercaptan, n-octyl mercaptan, and 2-
mercaptoethanol, titled "Determination of [beta]-Dodecyl-
mercaptopropionitrile in NR-16R Aqueous Extracts" and "Measurement of 
[beta]-(2-Hdroxyethylmercapto) Propionitrile in Heptane Food-Simulating 
Solvent," are incorporated by reference. Copies are available from the 
Center for Food Safety and Applied Nutrition (HFS-200), Food and Drug 
Administration, 5100 Paint Branch Pkwy., College Park, MD 20740, or 
available for inspection at the Office of the Federal Register, 800 
North Capitol Street, NW., suite 700, Washington, DC 20408.
    (c) The following data shall be provided for finished food-contact 
articles intended for repeated use:
    (1) Qualitative and quantitative migration values at a time 
equivalent to initial batch usage, utilizing solvents and temperatures 
appropriate to the intended conditions of use.
    (2) Qualitative and quantitative migration values at the time of 
equilibrium extractions, utilizing solvents and temperatures appropriate 
to the intended conditions of use.
    (3) Data on the volume and/or weight of food handled during the 
initial batch time period(s), during the equilibrium test period, and 
over the estimated life of the food-contact surface.
    (d) Where acrylonitrile copolymers represent only a minor component 
of a polymer system, calculations based on 100 percent migration of the 
acrylonitrile component may be submitted in lieu of the requirements of 
paragraphs (a), (b), and (c) of this section in support of the continued 
safe use of acrylonitrile copolymers.
    (e) On or before September 13, 1976, any interested person shall 
satisfy the Commissioner of Food and Drugs that toxicological feeding 
studies adequate and appropriate to establish safe conditions for the 
use of acrylonitrile copolymers have been, or soon will be,
 
[[Page 448]]
 
undertaken. Toxicity studies of acrylonitrile monomer shall include: (1) 
Lifetime feeding studies with a mammalian species, preferably with 
animals exposed in utero to the chemical, (2) studies of multigeneration 
reproduction with oral administration of the test material, (3) 
assessment of teratogenic and mutagenic potentials, (4) subchronic oral 
administration in a nonrodent mammal, (5) tests to determine any 
synergistic toxic effects between acrylonitrile monomer and cyanide ion, 
and (6) a literature search on the effects of chronic ingestion of 
hydrogen cyanide. Data on levels of acrylamide extractable from 
acrylonitrile copolymers shall also be submitted. Protocols of testing 
should be submitted for review to the Center for Food Safety and Applied 
Nutrition (HFS-200, Food and Drug Administration, 5100 Paint Branch 
Pkwy., College Park, MD 20740.
    (f) Acrylonitrile copolymers may be used in contact with food only 
if authorized in parts 174 through 179 or Sec. 181.32 of this chapter, 
except that other uses of acrylonitrile copolymers in use prior to June 
14, 1976, may continue under the following conditions:
    (1) On or before August 13, 1976, each use of acrylonitrile 
copolymers in a manner not authorized by Sec. 181.32 of this chapter or 
parts 174 through 179 of this chapter shall be the subject of a notice 
to the Center for Food Safety and Applied Nutrition (HFS-200), Food and 
Drug Administration, 5100 Paint Branch Pkwy., College Park, MD 20740. 
Such notice shall be accompanied by a statement of the basis, including 
any articles and correspondence, on which the user in good faith 
believed the use to be prior-sanctioned. The Commissioner of Food and 
Drugs shall, by notice in the Federal Register, identify any use of 
acrylonitrile copolymers not in accordance with this paragraph. Those 
uses are thereafter unapproved food additives and consequently unlawful.
    (2) Any use of acrylonitrile copolymers subject to paragraph (f)(1) 
of this section shall be the subject of a petition submitted on or 
before December 13, 1976, in accordance with Sec. 171.1 of this chapter, 
unless an extension of time is granted by the Food and Drug 
Administration for good cause shown. Any application for extension shall 
be by petition submitted in accordance with the requirements of part 10 
of this chapter. If a petition is denied, in whole or in part, those 
uses subject to the denial are thereafter unapproved food additives and 
consequently unlawful.
    (3) Any use of acrylonitrile copolymers subject to paragraph (f)(1) 
of this section shall meet the acrylonitrile monomer extraction 
limitation set forth in paragraph (a) of this section and shall be 
subject to the requirements of paragraph (b) of this section.
    (g) In addition to the requirements of this section, the use of 
acrylonitrile copolymers shall comply with all applicable requirements 
in other regulations in this part.
 
[42 FR 14636, Mar. 15, 1977, as amended at 47 FR 11850, Mar. 19, 1982; 
54 FR 24899, June 12, 1989; 61 FR 14246, Apr. 1, 1996]
 
 
 
 
 
[Code of Federal Regulations]
[Title 21, Volume 3]
[Revised as of April 1, 2003]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR180.25]
 
[Page 448-449]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                          SERVICES (CONTINUED)
 
PART 180--FOOD ADDITIVES PERMITTED IN FOOD OR IN CONTACT WITH FOOD ON AN INTERIM BASIS PENDING ADDITIONAL STUDY--Table of Contents
 
       Subpart B--Specific Requirements for Certain Food Additives
 
Sec. 180.25  Mannitol.
 
    (a) Mannitol is the chemical 1,2,3,4,5,6,-hexanehexol 
(C6H14O6) a hexahydric alcohol, 
differing from sorbitol principally by having a different optical 
rotation. Mannitol is produced by one of the following processes:
    (1) The electrolytic reduction or transition metal catalytic 
hydrogenation of sugar solutions containing glucose or fructose.
    (2) The fermentation of sugars or sugar alcohols such as glucose, 
sucrose, fructose, or sorbitol using the yeast Zygosaccharomyces rouxii.
    (b) The ingredient meets the specifications of the "Food Chemicals 
Codex," 3d Ed. (1981), pp. 188-190, which is incorporated by reference. 
Copies may be obtained from the National Academy Press, 2101 
Constitution Ave. NW., Washington, DC 20418, or may be examined at the 
Office of the Federal Register, 800 North Capitol Street, NW., suite 
700, Washington, DC 20408.
    (c) The ingredient is used as an anticaking agent and free-flow 
agent as defined in Sec. 170.3(o)(1) of this chapter, formulation aid as 
defined in Sec. 170.3(o) (14) of this chapter, firming agent as defined 
in Sec. 170.3(o)(10) of this chapter, flavoring agent and adjuvant as 
defined in Sec. 170.3(o)(12) of this chapter, lubricant and release 
agent as defined in
 
[[Page 449]]
 
Sec. 170.3(o)(18) of this chapter, nutritive sweetener as defined in 
Sec. 170.3(o)(21) of this chapter, processing aid as defined in 
Sec. 170.3(o)(24) of this chapter, stabilizer and thickener as defined 
in Sec. 170.3(o)(28) of this chapter, surface-finishing agent as defined 
in Sec. 170.3(o)(30) of this chapter, and texturizer as defined in 
Sec. 170.3(o)(32) of this chapter.
    (d) The ingredient is used in food at levels not to exceed 98 
percent in pressed mints and 5 percent in all other hard candy and cough 
drops as defined in Sec. 170.3(n)(25) of this chapter, 31 percent in 
chewing gum as defined in Sec. 170.3(n)(6) of this chapter, 40 percent 
in soft candy as defined in Sec. 170.3(n)(38) of this chapter, 8 percent 
in confections and frostings as defined in Sec. 170.3(n)(9) of this 
chapter, 15 percent in nonstandardized jams and jellies, commercial, as 
defined in Sec. 170.3(n)(28) of this chapter, and at levels less than 
2.5 percent in all other foods.
    (e) The label and labeling of food whose reasonably foreseeable 
consumption may result in a daily ingestion of 20 grams of mannitol 
shall bear the statement "Excess consumption may have a laxative 
effect".
    (f) In accordance with Sec. 180.1, adequate and appropriate feeding 
studies have been undertaken for this substance. Continued uses of this 
ingredient are contingent upon timely and adequate progress reports of 
such tests, and no indication of increased risk to public health during 
the test period.
    (g) Prior sanctions for this ingredient different from the uses 
established in this regulation do not exist or have been waived.
 
[42 FR 14636, Mar. 15, 1977, as amended at 49 FR 5610, Feb. 14, 1984; 61 
FR 7991, Mar. 1, 1996]
 
 
 
 
 
[Code of Federal Regulations]
[Title 21, Volume 3]
[Revised as of April 1, 2003]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR180.30]
 
[Page 449]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                          SERVICES (CONTINUED)
 
PART 180--FOOD ADDITIVES PERMITTED IN FOOD OR IN CONTACT WITH FOOD ON AN INTERIM BASIS PENDING ADDITIONAL STUDY--Table of Contents
 
       Subpart B--Specific Requirements for Certain Food Additives
 
Sec. 180.30  Brominated vegetable oil.
 
    The food additive brominated vegetable oil may be safely used in 
accordance with the following prescribed conditions:
    (a) The additive complies with specifications prescribed in the 
"Food Chemicals Codex," 3d Ed. (1981), pp. 40-41, which is 
incorporated by reference, except that free fatty acids (as oleic) shall 
not exceed 2.5 percent and iodine value shall not exceed 16. Copies of 
the material incorporated by reference may be obtained from the National 
Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418, or may 
be examined at the Office of the Federal Register, 800 North Capitol 
Street, NW., suite 700, Washington, DC 20418.
    (b) The additive is used on an interim basis as a stabilizer for 
flavoring oils used in fruit-flavored beverages, for which any 
applicable standards of identity do not preclude such use, in an amount 
not to exceed 15 parts per million in the finished beverage, pending the 
outcome of additional toxicological studies on which periodic reports at 
6-month intervals are to be furnished and final results submitted to the 
Food and Drug Administration promptly after completion of the studies.
 
[42 FR 14636, Mar. 15, 1977, as amended at 49 FR 5610, Feb. 14, 1984]
 
 
 
 
 
[Code of Federal Regulations]
[Title 21, Volume 3]
[Revised as of April 1, 2003]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR180.37]
 
[Page 449-450]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                          SERVICES (CONTINUED)
 
PART 180--FOOD ADDITIVES PERMITTED IN FOOD OR IN CONTACT WITH FOOD ON AN INTERIM BASIS PENDING ADDITIONAL STUDY--Table of Contents
 
       Subpart B--Specific Requirements for Certain Food Additives
 
Sec. 180.37  Saccharin, ammonium saccharin, calcium saccharin, and sodium saccharin.
 
    The food additives saccharin, ammonium saccharin, calcium saccharin, 
and sodium saccharin may be safely used as sweetening agents in food in 
accordance with the following conditions, if the substitution for 
nutritive sweeteners is for a valid special dietary purpose and is in 
accord with current special dietary food regulations and policies or if 
the use or intended use is for an authorized technological purpose other 
than calorie reduction:
    (a) Saccharin is the chemical, 1,2-benzisothiazolin-3-one - 1,1 - 
dioxide (C7H5NO3S). The named salts of 
saccharin are produced by the additional neutralization of saccharin 
with the proper base to yield the desired salt.
    (b) The food additives meet the specifications of the "Food 
Chemicals Codex," 3d Ed. (1981), pp. 22, 62, 266-267, 297-299, which is 
incorporated by reference. Copies may be obtained from the National 
Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418, or may 
be examined at the Office of the Federal Register, 800 North Capitol 
Street, NW., suite 700, Washington, DC 20408.
    (c) Authority for such use shall expire when the Commissioner 
receives the final reports on the ongoing studies in Canada and 
publishes an order on the safety of saccharin and its salts
 
[[Page 450]]
 
based on those reports and other available data.
    (d) The additives are used or intended for use as a sweetening agent 
only in special dietary foods, as follows:
    (1) In beverages, fruit juice drinks, and bases or mixes when 
prepared for consumption in accordance with directions, in amounts not 
to exceed 12 milligrams of the additive, calculated as saccharin, per 
fluid ounce.
    (2) As a sugar substitute for cooking or table use, in amounts not 
to exceed 20 milligrams of the additive, calculated as saccharin, for 
each expressed teaspoonful of sugar sweetening equivalency.
    (3) In processed foods, in amounts not to exceed 30 milligrams of 
the additive, calculated as saccharin, per serving of designated size.
    (e) The additives are used or intended for use only for the 
following technological purposes:
    (1) To reduce bulk and enhance flavors in chewable vitamin tablets, 
chewable mineral tablets, or combinations thereof.
    (2) To retain flavor and physical properties of chewing gum.
    (3) To enhance flavor of flavor chips used in nonstandardized bakery 
products.
    (f) To assure safe use of the additives, in addition to the other 
information required by the Act:
    (1) The label of the additive and any intermediate mixes of the 
additive for manufacturing purposes shall bear:
    (i) The name of the additive.
    (ii) A statement of the concentration of the additive, expressed as 
saccharin, in any intermediate mix.
    (iii) Adequate directions for use to provide a final food product 
that complies with the limitations prescribed in paragraphs (d) and (e) 
of this section.
    (2) The label of any finished food product containing the additive 
shall bear:
    (i) The name of the additive.
    (ii) The amount of the additive, calculated as saccharin, as 
follows:
    (a) For beverages, in milligrams per fluid ounce;
    (b) For cooking or table use products, in milligrams per dispensing 
unit;
    (c) For processed foods, in terms of the weight or size of a serving 
which shall be that quantity of the food containing 30 milligrams or 
less of the additive.
    (iii) When the additive is used for calorie reduction, such other 
labeling as is required by part 105 or Sec. 100.130 of this chapter.
 
[42 FR 14636, Mar. 15, 1977, as amended at 49 FR 5610, Feb. 14, 1984]