0298 21cfr170

§ 170.39

21 CFR Ch. I (4–1–06 Edition)

of such an applicable prior sanction in
response to the proposal.

the Food and Drug Administration’s
files or from other appropriate sources;
(3) The substance has no technical effect in or on the food to which it migrates; and
(4) The substance use has no significant adverse impact on the environment.
(b) Notwithstanding paragraph (a) of
this section, the Food and Drug Administration reserves the right to decline
to grant an exemption in those cases in
which available information establishes that the proposed use may pose a
public health risk. The reasons for the
agency’s decision to decline to grant an
exemption will be explained in the
Food and Drug Administration’s response to the requestor.
(c) A request for the Food and Drug
Administration to exempt a use of a
substance from regulation as a food additive shall include three copies of the
following information (If part of the
submitted material is in a foreign language, it must be accompanied by an
English translation verified to be complete and accurate in accordance with
§ 10.20(c)(2) of this chapter):
(1) The chemical composition of the
substance for which the request is
made, including, whenever possible,
the name of the chemical in accordance with current Chemical Abstract
Service (CAS) nomenclature guidelines
and a CAS registry number, if available;
(2) Detailed information on the conditions of use of the substance (e.g.,
temperature, type of food with which
the substance will come into contact,
the duration of the contact, and whether the food-contact article will be for
repeated or single use applications);
(3) A clear statement as to whether
the request for exemption from regulation as a food additive is based on the
fact that the use of the substance in
the food-contact article results in a dietary concentration at or below 0.5
parts per billion, or on the fact that it
involves the use of a regulated direct
food additive for which the dietary exposure is at or below 1 percent of the
acceptable dietary intake (ADI);
(4) Data that will enable the Food
and Drug Administration to estimate

[42 FR 14488, Mar. 15, 1977, as amended at 42
FR 15673, Mar. 22, 1977; 54 FR 24896, June 12,
1989]

§ 170.39 Threshold of regulation for
substances used in food-contact articles.
(a) A substance used in a food-contact article (e.g., food-packaging or
food-processing equipment) that migrates, or that may be expected to migrate, into food will be exempted from
regulation as a food additive because it
becomes a component of food at levels
that are below the threshold of regulation if:
(1) The substance has not been shown
to be a carcinogen in humans or animals, and there is no reason, based on
the chemical structure of the substance, to suspect that the substance is
a carcinogen. The substance must also
not contain a carcinogenic impurity or,
if it does, must not contain a carcinogenic impurity with a TD50 value based
on chronic feeding studies reported in
the scientific literature or otherwise
available to the Food and Drug Administration of less than 6.25 milligrams
per kilogram bodyweight per day (The
TD50, for the purposes of this section, is
the feeding dose that causes cancer in
50 percent of the test animals when
corrected for tumors found in control
animals. If more than one TD50 value
has been reported in the scientific literature for a substance, the Food and
Drug Administration will use the lowest appropriate TD50 value in its review.);
(2) The substance presents no other
health or safety concerns because:
(i) The use in question has been
shown to result in or may be expected
to result in dietary concentrations at
or below 0.5 parts per billion, corresponding to dietary exposure levels
at or below 1.5 micrograms/person/day
(based on a diet of 1,500 grams of solid
food and 1,500 grams of liquid food per
person per day); or
(ii) The substance is currently regulated for direct addition into food, and
the dietary exposure to the substance
resulting from the proposed use is at or
below 1 percent of the acceptable daily
intake as determined by safety data in

18

VerDate Aug<31>2005

02:24 Apr 21, 2006

Jkt 208067

PO 00000

Frm 00028

Fmt 8010

Sfmt 8010

Y:\SGML\208067.XXX

208067

Food and Drug Administration, HHS

§ 170.39

the daily dietary concentration resulting from the proposed use of the substance. These data should be in the
form of:
(i) Validated migration data obtained
under worst-case (time/temperature)
intended use conditions utilizing appropriate food simulating solvents;
(ii) Information on the amount of the
substance used in the manufacture of
the food-contact article; or
(iii) Information on the residual level
of the substance in the food-contact article. For repeat-use articles, an estimate of the amount of food that contacts a specific unit of surface area
over the lifetime of the article should
also be provided. (In cases where data
are provided only in the form of manufacturing use levels or residual levels
of the substance present in the foodcontact article, the Food and Drug Administration will calculate a worstcase dietary concentration level assuming 100 percent migration.) A detailed description of the analytical
method used to quantify the substance
should also be submitted along with
data used to validate the detection
limit.
(iv) In cases where there is no detectable migration into food or food
simulants, or when no residual level of
a substance is detected in the food-contact article by a suitable analytical
method, the Food and Drug Administration will, for the purposes of estimating the dietary concentration, consider the validated detection limit of
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 pro-

posed 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 Division of Dockets
Management. 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 Division of Dockets
Management
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

19

VerDate Aug<31>2005

02:24 Apr 21, 2006

Jkt 208067

PO 00000

Frm 00029

Fmt 8010

Sfmt 8010

Y:\SGML\208067.XXX

208067

§ 170.45

21 CFR Ch. I (4–1–06 Edition)

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 Division of Dockets Management
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 (HFS–
200), 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]

Subpart C—Specific Administrative Rulings and Decisions
§ 170.45 Fluorine-containing
compounds.
The Commissioner of Food and Drugs
has concluded that it is in the interest
of the public health to limit the addition of fluorine compounds to foods (a)
to that resulting from the fluoridation
of public water supplies as stated in
§ 250.203 of this chapter, (b) to that resulting 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

20

VerDate Aug<31>2005

02:24 Apr 21, 2006

Jkt 208067

PO 00000

Frm 00030

Fmt 8010

Sfmt 8010

Y:\SGML\208067.XXX

208067