[Code of Federal Regulations]
[Title 21, Volume 3]
[Revised as of January 1, 2007]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR170.39]
[Page 18-20]
TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
SERVICES (CONTINUED)
PART 170_FOOD ADDITIVES--Table of Contents
Subpart B_Food Additive Safety
Sec. 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 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
Sec. 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
[[Page 19]]
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 food-contact article, the Food and Drug
Administration will calculate a worst-case 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 proposed use of the substance. The request should contain either a
claim for categorical exclusion as specified in Sec. 25.32 of this
chapter or an environmental assessment as specified in Sec. 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 Sec. 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
[[Page 20]]
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 Sec. 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 Sec. 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 food-contact 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]