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Federal Register / Vol. 60, No. 136 / Monday, July 17, 1995 / Rules and Regulations

DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 5, 25, 170, 171, and 174
[Docket Nos. 77P–0122 and 92N–0181]

Food Additives; Threshold of
Regulation for Substances Used in
Food-Contact Articles
AGENCY: Food and Drug Administration,

HHS.
ACTION: Final rule.
SUMMARY: The Food and Drug
Administration (FDA) is amending its
food additive regulations to establish a
process for determining when the
likelihood or extent of migration to food
of a substance used in a food-contact
article is so trivial as not to require
regulation of the substance as a food
additive. Although still a ‘‘food
additive,’’ a substance exempted from
regulation under this process will not be
required to be the subject of a food
additive listing regulation. Under this
process, information about the proposed
use of the substance will undergo an
abbreviated review by FDA, as opposed
to the extensive review normally
required for food additives. This final
rule also lists the criteria that FDA will
use in its review in deciding whether it
is necessary to regulate the use of a
substance as a food additive and
identifies the types of data that it will
need to make this determination.
EFFECTIVE DATE: August 16, 1995.
FOR FURTHER INFORMATION CONTACT:
Edward J. Machuga, Center for Food
Safety and Applied Nutrition (HFS–
216), Food and Drug Administration,
200 C St. SW., Washington, DC 20204,
202–418–3085.
SUPPLEMENTARY INFORMATION:

I. Background
In the Federal Register of October 12,
1993 (58 FR 52719), the agency
proposed to establish a process for
determining when the likelihood or
extent of migration to food of a
substance used in a food-contact article
is so trivial as not to require regulation
of the substance as a food additive. The
proposal was in response to a number
of comments from representatives of the
food packaging and processing
industries suggesting that FDA establish
a threshold of regulation policy whereby
those substances used in food-contact
articles that result in minimal migration
into food would be exempt from
regulation as food additives.
The proposal also responded to a
citizen petition (Docket No. 77P–0122)

submitted by the Society of the Plastics
Industry, Inc., requesting that FDA
modify § 170.3(e) (21 CFR 170.3(e)), the
regulation that defines ‘‘food additive,’’
to provide that the use of a substance
that does not result in detectable levels
of migration into food-simulating
solvents (using validated analytical
methods sensitive to at least 50 parts per
billion (ppb)) would be exempt from
regulation as a food additive unless
there is scientific evidence that the
substance presents a significant risk of
harm to human health.
Traditionally, FDA had been reluctant
to adopt any of these suggestions in the
absence of data that clearly show that
substances present in the daily diet at
concentrations at or below the proposed
threshold level would not pose safety
concerns. However, data on the toxic
effects of a large number of
representative compounds have become
available over the last 5 to 10 years that
have made it possible for FDA to
evaluate the feasibility of establishing a
threshold of regulation for food-contact
articles. These data show that
noncarcinogenic and carcinogenic toxic
effects usually occur within predictable
ranges of dietary exposure. They make
it possible to identify a specific level of
dietary exposure that is well below the
range of dietary exposures that typically
induce toxic effects and, therefore, that
poses only negligible safety concerns.
This level can function as the
‘‘threshold of regulation’’ for
components of food-contact articles.
A Federal court has addressed the
issue of whether the use of a foodcontact material that results in
migration into food at insignificant
levels can be exempted from regulation
as a food additive. In Monsanto v.
Kennedy, 613 F.2d 947 (D.C. Cir. 1979),
the Monsanto Co. contended that no
detectable migration of acrylonitrile
copolymer resulted from the use of their
beverage bottles that contained the
substance, and that, therefore, the
copolymer did not have to be regulated
as a food additive. In its decision, the
court stated that the Commissioner of
Food and Drugs (the Commissioner)
may determine that the level of
migration into food of a particular
substance is so negligible as to present
no public health or safety concerns and,
in such cases, may decline to define the
substance as a food additive even
though it comes within the strictly
literal terms of the statutory definition
of a food additive (613 F.2d at 956). The
court also stated that the Commissioner
has the discretion not to exercise this
exemption authority (id.).
Based on available toxicological data
showing that it is feasible to establish a

threshold level below which dietary
exposures to substances used in foodcontact articles are so negligible as to
pose no public health or safety
concerns, the discretionary authority of
the Commissioner to exempt those
substances that present no public health
concerns from regulation as food
additives, and the agency’s
consideration of the comments that it
received on the October 12, 1993,
proposal, FDA is amending the food
additive regulations to establish a
process for determining when the
likelihood or extent of migration to food
of a substance used in a food-contact
article is so trivial as not to require that
the substance be regulated as a food
additive.
As part of this process, the agency is
establishing two types of thresholds for
the regulation of substances used in
food-contact articles. The first type of
threshold will exempt from regulation
those substances whose use in foodcontact articles results in a dietary
concentration of the substance of 0.5
ppb or less. The second type of
threshold will exempt regulated direct
food additives from regulation when
used in food-contact articles at levels
that result in a dietary exposure of 1
percent or less of the acceptable daily
intake (ADI) for the additive.
II. Comments on the Proposed Rule
The agency provided 60 days for
comment on the proposed rule. It
received two requests from industry for
an extension of the comment period.
The agency granted a 60-day extension
of the comment period to February 11,
1994, in a notice published in the
Federal Register of December 13, 1993
(58 FR 65139).
FDA received 20 comments from the
food packaging industry and trade
associations that represent the plastics
and paper industries. One of these
comments concerned the economic
impact of the proposed action. This
comment is discussed in section IV of
this document. The other issues raised
in the comments, and the agency’s
response to them, are set forth below.
A. The Exemption
Appropriateness of the 0.5 PPB
Threshold Level for Components of
Food-Contact Articles
1. Eight comments expressed the
opinion that the 0.5 ppb threshold is
more conservative and restrictive than is
necessary to adequately protect the
public health. In general, these
comments expressed the view that
current scientific data support the

Federal Register / Vol. 60, No. 136 / Monday, July 17, 1995 / Rules and Regulations
establishment of a dietary concentration
higher than 0.5 ppb as the threshold.
The agency does not agree that a 0.5
ppb threshold is unduly conservative,
especially in light of the fact that a
substance being considered for an
exemption may not have been the
subject of any toxicological testing. As
discussed in the proposed rule,
carcinogenic toxic effects in test animals
typically occur at lower dietary
concentrations than the levels at which
noncarcinogenic toxic effects occur.
Therefore, FDA’s goal has been to
establish a threshold that is low enough
to ensure that even if an unstudied
compound that is exempted from
regulation is later shown to be a
carcinogen, its use would not have
represented any more than a negligible
risk to the public health.
Although eight comments were
received that expressed the opinion that
the 0.5 ppb threshold is more
conservative and restrictive than is
necessary to adequately protect the
public health, no data were provided in
any of these comments to show that a
threshold significantly higher than 0.5
ppb is adequate to ensure that
substances present in the diet at or
below the threshold would pose only
negligible safety concerns. Therefore, as
proposed, this final rule establishes 0.5
ppb as the threshold of regulatory
concern for substances used in foodcontact articles. We will reconsider this
threshold if we receive new data that
justify a higher level.
2. One comment objected to the
agency’s apparent use of a 200-fold
safety factor when applying to humans
the results of studies showing the
noncarcinogenic toxic effects observed
in animals subjected to chronic
chemical exposure. The comment stated
that FDA guidelines employ only a 100fold safety factor. The comment argued
that the use of the 100-fold safety factor
would allow FDA to establish a
threshold of regulatory concern higher
than 0.5 ppb.
The agency emphasizes that it did not
base its proposed threshold on
noncarcinogenic toxic endpoints, and
that, therefore, it did not employ the
safety factor approach typically used
when applying to humans the results of
studies showing the noncarcinogenic
toxic effects observed in animals
subjected to chronic chemical exposure.
Because carcinogenic effects typically
occur in test animals at lower dietary
concentrations than those at which
noncarcinogenic toxic effects occur, as
stated above, FDA’s goal was to
establish a threshold that is low enough
to ensure that substances that are
exempted from regulation under it will

pose only negligible safety concerns
even if they are ultimately shown to
have carcinogenic effects.
Based on its analysis of the
carcinogenic potencies of 477
chemicals, and using the assumptions
that the distribution of carcinogenic
potencies of the 477 chemicals studied
are representative of all known and
unknown carcinogens, and that it is
very unlikely that an unstudied
compound would both: (1) Be a
carcinogen and (2) have an intrinsic
carcinogenic potency far greater than
the typical potency observed for the
studied compounds, FDA has
determined that, if an exempted
substance present in the diet at 0.5 ppb
were later found to be a carcinogen, the
upper-bound lifetime risk resulting from
the use of the substance is likely to be
below one in a million. This level of risk
is generally regarded as very low (i.e.,
one that poses only negligible safety
concerns). Because carcinogenic effects
typically occur at lower dietary
concentrations than those at which
noncarcinogenic toxic effects occur, an
0.5 ppb threshold would ensure that
substances that pass under it pose
negligible safety concerns from
noncarcinogenic toxic effects as well.
However, the fact that a 0.5 ppb
threshold level happens to be 200,
rather than a 100, times lower than the
chronic exposure level at which potent
pesticides induce noncarcinogenic toxic
effects is merely coincidental and does
not reflect the agency’s reasoning.1
3. One comment expressed the
opinion that the threshold should have
been based on the mean TD502 value of
the 477 known carcinogens that were
the subject of FDA analysis as opposed
to the most probable TD50 value. This
comment stated that the use of a mean
TD50 would allow FDA to establish a
threshold significantly higher than 0.5
ppb.
FDA does not agree that it is
appropriate to establish a threshold
level based on the mean TD50 value of
the 477 known carcinogens that were
the subject of FDA’s analysis because
this approach would give inappropriate
weight to carcinogens with high TD50
1 The agency typically uses a 100-fold safety
factor when applying to humans the results of
animal data obtained from long term exposure to a
chemical (i.e., 2-year chronic feeding studies). Short
term toxicological testing (i.e., 90-day subchronic
feeding studies) may not always be long enough to
show all of the toxic effects that may be induced
by long term exposure to a chemical, and, therefore,
in such cases, FDA often uses higher safety factors
(1000-fold to 2000-fold).
2 The TD , for the purposes of this regulation, is
50
the feeding dose that causes cancer in 50 percent
of the test animals when corrected for tumors found
in control animals.

36583

values. Because the carcinogenic
potency of a substance is inversely
related to its TD50 value, this approach
would give too much emphasis to
carcinogens with low potencies. A more
meaningful approach to estimating the
likelihood that a substance will pose a
potential health hazard at a given
dietary concentration is to use the
potency that it is most likely to have if
it were later found to be a carcinogen.
Because such an approach would be
based on the frequency distribution of
the potencies of a large number of
carcinogens (i.e., a distribution showing
the number of carcinogens whose
potencies occur within particular
dietary concentration ranges) and would
not be based on the magnitude of the
potencies themselves, this approach
would not give undue weight to
carcinogens with low potencies (i.e.,
high TD50 values).
In arriving at a threshold of
regulation, FDA’s analysis of the
potencies of 477 animal carcinogens
consisted in part of grouping them by
dietary concentration ranges (Ref. 1).
The agency plotted the potencies as a
probability distribution on a
semilogarithmic scale and found that
they formed a bell-shaped distribution
curve. Using this probability
distribution for carcinogenic potencies,
FDA determined that most known
carcinogens pose less than one in a
million upper-bound lifetime risk if
present in the daily diet at 0.5 ppb or
less.
4. One comment expressed the view
that it was unlikely that a given
packaging material would be present in
the daily diet over the course of a
lifetime. It asserted that, therefore, FDA
should not have based its threshold on
potential lifetime carcinogenic risks.
Because of the changing technology
associated with the food-packaging
industry, FDA agrees that is not always
possible to predict whether a given type
of packaging material is likely to be
present in the daily diet over the course
of a lifetime. However, because many of
the substances considered for an
exemption from regulation will not have
been the subject of any toxicological
testing, it is imperative, in establishing
a threshold level, to use an approach
that is not likely to underestimate the
risk associated with the use of such
additives. Therefore, the agency used an
approach that assumed that a given
packaging material would be present in
the daily diet for an entire lifetime.
Lifetime upper-bound risks have
traditionally been used by FDA to assess
the overall safety of packaging materials
containing small amounts of
carcinogenic impurities, and the agency

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believes that it is appropriate to use a
similar approach in assessing the
likelihood of potential carcinogenic
effects associated with substances
exempted from regulation. Based on its
analysis of the potencies of 477 known
carcinogens and the lifetime upperbound risks that they would pose if
present in the daily diet over a lifetime,
FDA has determined that a substance
present in the daily diet for a lifetime at
0.5 ppb would pose only negligible risk
even if it were later shown to be a
carcinogen. Because of the
conservatisms used by the agency in its
approach to determining a threshold
level, FDA is confident that an
exempted substance present in the daily
diet for a lifetime at 0.5 ppb would pose
no regulatory concern.
5. Four of the comments
recommended that FDA establish a
higher threshold for substances that
have been shown to be nonmutagenic or
to have relatively high LD503 values. For
example, one comment recommended
that for substances that have been
shown to be nonmutagenic and to have
LD50 values greater than 2,000
milligrams per kilogram (mg/kg), the
threshold should be raised to 5 ppb.
FDA agrees with these comments that
it may be possible to establish separate
thresholds for compounds that have
been the subject of toxicological tests
that show that they are nonmutagenic,
or that they have high LD50 values.
However, a direct correlation will need
to be firmly established showing that
such compounds, if carcinogenic, are
likely to be less potent than those that
have been shown to be mutagenic or to
have lower LD50 values. Such a
correlation would provide confirmation
that a substance that has been shown to
be nonmutagenic or to have a high LD50
value poses a significantly lower risk
from potential carcinogenic effects
when present in the daily diet at the
same level than one that has been
shown to be mutagenic or to have a low
LD50 value.
The correlation between mutagenicity
or acute toxicity and carcinogenic
potency is the subject of ongoing FDA
analysis. If the results of FDA’s analysis
confirm that the likelihood that a
substance poses a significant risk from
potential carcinogenic effects is
significantly lower when that substance
has been shown to be nonmutagenic or
to have a high LD50 value, it may be
possible to establish a threshold for
such substances that is higher than 0.5
ppb but that still ensures that their use
3 The LD
50 is the dose in acute feeding studies
that causes lethality in 50 percent of the test
animals.

in food-contact articles will pose only
negligible health concerns.
6. Three comments suggested that
FDA establish a higher threshold for
compounds that do not possess
structural concerns (i.e., that do not
possess structural similarities to known
carcinogens).
In general, the principle behind the
use of quantitative structure activity
relationships is that the analysis of the
toxicity of a large number of compounds
of known structure enables one to
predict the relative toxicity of unstudied
compounds based on the degree of
similarity in chemical structure to
studied compounds. While FDA may
use structure activity relationships to
ascertain whether there is a basis to
suspect that a substance is a carcinogen,
knowledge about such relationships is
not reliable enough at this time to justify
reliance on an analysis of them to
establish a higher threshold of
regulation for some compounds. The
comments did not submit any evidence
to support a contrary conclusion.
7. Three comments recommended that
the threshold be raised for compounds
that have been shown to be
noncarcinogenic. For example, one
comment recommended that the
threshold be raised to 100 ppb for
substances that have been shown to be
negative in 2-year bioassays.
FDA agrees that it may be possible in
the future to establish a threshold higher
than 0.5 ppb for substances that have
been shown to be noncarcinogenic
based on results obtained from
appropriate 2-year bioassays. As
discussed above, carcinogenic effects in
test animals typically occur at lower
dietary concentrations than do
noncarcinogenic toxic effects. Therefore,
FDA proposed to establish 0.5 ppb as
the dietary concentration threshold
because this level is low enough to
preclude the likelihood of all but
negligible risk even if an unstudied
compound is later shown to be a
carcinogen. In the case of
noncarcinogens, however, the threshold
of regulation could be based solely on
the level at, and below which,
noncarcinogenic toxic effects are
unlikely to occur.
As stated in the proposed rule (58 FR
52719 at 52722), FDA’s analysis of the
data on 18,000 acute oral feeding
studies in rats and mice found that all
of the acute toxic effects occurred above
1,000 ppb. The results of 2-year chronic
oral feeding studies on 220 compounds
have shown that only 5 of the 220
chemicals exhibited toxic effects below
1,000 ppb, and that all 5 of these
chemicals were pesticides, compounds
that are expected to be more toxic than

most substances. Even for these five
pesticides, none exhibited toxic effects
at dietary concentrations below 100
ppb. These results suggest that it may be
feasible to establish a separate threshold
for substances that have been
appropriately tested and found not to be
carcinogens. Such a threshold would
likely be well below the level at which
noncarcinogenic toxic effects are likely
to occur but higher than the 0.5 ppb
threshold that FDA is establishing to
minimize the risk from potential
carcinogens. FDA is not establishing a
separate threshold for noncarcinogenic
substances at this time, however,
because the number of chemicals,
particularly pesticides, that have been
analyzed is not sufficient to ensure that
the results of this analysis are
representative of substances used in the
manufacture of food-contact articles. An
analysis of the dietary concentrations at
which a large number and a wide
variety of potent toxicants, such as
pesticides, exhibit noncarcinogenic
toxic effects is needed before FDA can
determine whether establishment of a
threshold significantly higher than 0.5
ppb for noncarcinogenic substances is
justified.
Appropriateness of the 1-Percent ADI
Threshold for Regulated Direct
Additives
8. One comment recommended that
once the final rule has been established,
and the policy has been put into
practice for a time, FDA should reassess
the 1 percent of the ADI threshold for
regulated direct food additives used in
food-contact articles to see whether this
threshold can be raised.
As stated in the proposal, a 1-percent
ADI threshold for regulated direct food
additives used in food-contact articles is
appropriate because this level of dietary
exposure will contribute only a small
fraction of the ADI of a substance and,
therefore, will be well within the margin
of safety for those direct food additives
with small cumulative dietary
exposures. For substances with high
cumulative dietary exposures resulting
from regulated direct food additive uses,
a level of exposure that is 1 percent of
the ADI would be within the margin of
error for the estimated daily intake. It
would, therefore, not significantly affect
the cumulative dietary exposure, even
in the event that a particular substance
is granted exemptions for several
different types of uses in food-contact
articles.
The agency would like to emphasize
that no comments were received that
expressed any safety concern about the
1 percent of the ADI threshold. As for
raising this threshold above the 1-

Federal Register / Vol. 60, No. 136 / Monday, July 17, 1995 / Rules and Regulations
percent ADI level, FDA’s main concern
is with those cases in which a particular
substance may be granted exemptions
for a number of different types of new
uses, each of which results in a dietary
exposure at or near the threshold level.
In such cases, the dietary exposure
resulting from all of the exempted uses
could represent a significant increase in
the cumulative dietary exposure for the
substance and, in cases where the
estimated dietary intake from currently
regulated uses is close to the ADI, may
not be supported by existing safety data.
It is possible, however, that once the
threshold of regulation process is put
into practice, other factors will surface
that mitigate the agency’s concerns on
this issue. If the latter situation proves
to be the case, the agency may find it
appropriate to reassess the 1 percent of
the ADI threshold for regulated direct
food additives used in food-contact
articles.
9. One comment recommended that
FDA publish or otherwise make
available the ADI’s for currently
regulated direct food additives. In cases
where such ADI’s are not readily
available, FDA should consider other
sources (e.g., the European Union’s
Scientific Committee for Foods) or
provide guidelines for the calculation of
appropriate ADI’s.
FDA agrees that the ADI’s for
currently regulated direct food additives
should be made more readily available.
Therefore, FDA plans to incorporate this
information into its priority based
assessment of food additives (PAFA)
data base and make this data base
accessible to the public (Ref. 2). In the
meantime, requestors can obtain this
type of information on a specific
substance by submitting a written
request to FDA’s Office of Premarket
Approval (HFS–200, 200 C St. SW.,
Washington, DC 20204). In some cases,
especially for those uses of direct
additives that result in low dietary
exposures such as flavoring agents, FDA
may not have an ADI in its files.
Therefore, in those relatively few cases
where FDA does not have an
appropriate ADI for a regulated direct
food additive, the agency would
consider the use of an ADI value from
another appropriate source, such as the
Joint World Health Organization/Food
and Agriculture Organization (WHO/
FAO), Expert Committee on Food
Additives, or the European Union’s
Scientific Committee for Foods,
assuming that the data or other
information on which that ADI value is
based are also available. FDA is revising
proposed § 170.39(a)(2)(ii) to state that
FDA may use other appropriate sources
for ADI values.

FDA disagrees with the comment’s
suggestion that the agency provide
guidelines for the calculation of
appropriate ADI’s for review under the
process specified in this final rule.
Regulated direct food additives for
which an appropriate ADI does not exist
are not suitable candidates for an
abbreviated review under the threshold
of regulation process. This process is
not appropriate for reviewing
submissions containing detailed toxicity
studies on a substance for the purpose
of calculating an ADI value or for
verifying an ADI value calculated by the
requestor. Such extensive reviews are
better handled by the food additive
petition process.
10. One comment recommended that
FDA expand the proposed threshold of
regulation process for regulated direct
food additives to include exemptions for
direct uses in food, provided the dietary
exposures from such uses do not exceed
1 percent of the ADI. The proposed rule
limited such exemptions to only those
uses that may result in their indirectly
becoming components of food (i.e.,
resulting from their use in food-contact
articles).
FDA does not agree that the final rule
should be expanded in this manner.
There is a fundamental difference in
regulatory significance between
substances that are deliberately added
directly to food to accomplish a
technical effect in the food and
substances that are used in food-contact
articles in a manner such that they may
reasonably be expected to become
components of food indirectly and to
have no technical effect in that food.
The purpose of the food additive
provisions of the act is to ensure that
substances added to food are safe and
will have their intended technical effect
in the food that is to be consumed (S.
Rept. 2422, 85th Cong., August 18,
1958). Thus, given this purpose, there
simply would not be circumstances in
which a direct additive would be of
such little regulatory concern as to
justify application to it of the de
minimis 4 doctrine that underlies the
threshold of regulation concept (see
Monsanto v. Kennedy, supra). For
indirect food additives, in contrast, the
substance is being used for its technical
effect in a food-contact article, not in an
article that will itself be consumed.
Moreover, on occasion, it is
foreseeable that, while the exact amount
of an indirect additive that will get into
food is unclear, it will not exceed an
extremely small amount. It is in the
4 This doctrine is expressed in Latin as de
minimis non curat lex (the law does not concern
itself with trifles).

36585

latter circumstances that it is fair to say
that, given the purposes of the Federal
Food, Drug, and Cosmetic Act (the act),
the use of the substance is of no
significant regulatory concern, and thus
the use can be exempted from regulation
under the food additive provisions of
the act. In light of the purposes of the
food additive provisions, however, FDA
concludes that it is not appropriate to
extend the threshold of regulation
concept to substances intended for
direct use in food.
11. One comment expressed the
opinion that the proposed regulation is
unduly restrictive for the use of
regulated direct food additives in foodcontact articles when the direct additive
does not have any specific use level
restrictions. An example of the type of
situation raised by the comment would
be flavoring agents where the level of
their use in food would be self limiting
(i.e., use at high levels would make the
food unpalatable, and, therefore, FDA
did not find it necessary to impose
specific maximum use levels as part of
the regulations authorizing the use of
such substances). The comment
emphasized that, because of the time
required to obtain FDA approval (as a
result of FDA’s current backlog of work),
the consumer’s access to new packaging
technologies is often delayed. Not
requiring premarket approval of such
substances would save FDA resources,
reduce the backlog of work, and enable
the consumer to have quicker access to
new packaging formulations.
The comment argued that, based on
the extremely small levels of dietary
exposure that would result from the use
of direct additives in food-contact
articles, particularly in comparison to
the levels of exposure that result from
the direct uses of these substances, and
based on the fact that direct food
additives have been the subject of
extensive safety testing, FDA should
modify § 174.5(d) (21 CFR 174.5(d)) to
allow those direct food additives that
are regulated without specific use level
limitations to be used as components of
food-contact articles. The comment
asserted, however, that four restrictions
on such use were appropriate: (1) The
use of the substance in a food-contact
article must not result in a dietary
exposure that exceeds 1 percent of the
ADI for that substance; (2) the use level
must not exceed good manufacturing
practice (GMP) or that necessary to
accomplish the intended technical
effect; (3) the substance must be of a
purity suitable for the intended use; and
(4) the technical effect for such
additives must be as a formulation aid
or some other technical effect for which
the substance has been listed as a direct

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food additive (e.g., a substance
approved for use as a stabilizer and
thickener in food would be allowed to
be used as a stabilizer and thickener in
the manufacture of food-contact
articles). The comment cited FDA’s
approach to handling generally
recognized as safe (GRAS) substances as
a precedent for this approach. Under 21
CFR 186.1(a), ingredients affirmed as
GRAS for direct use in part 184 (21 CFR
part 184) are also affirmed as GRAS for
use as indirect human food ingredients
in accordance with § 184.1(a).
The agency notes that the issue raised
by this comment is outside the scope of
the proposed threshold of regulation
process. The comment is about whether
the uses in question should be approved
as food additive uses, not about whether
they should be exempted from
regulation under the food additive
provisions of the act.
Although outside the scope of this
rulemaking, FDA would like to
comment on the merits of the approach
recommended in this comment because
the agency is always interested in
evaluating ways that may help it to
more effectively implement the food
additive provisions of the act. FDA’s
main concern with the recommended
approach is that those direct food
additives that are regulated without
specific use level limitations, and which
meet the other restrictions specified in
this comment, could be used as
components of food-contact articles
without any further safety review by
FDA. Although it is true that the dietary
exposure resulting from the use of a
substance added directly to food is
usually much higher than that resulting
from the use of that substance as a
component of a food-contact article, the
existing safety data in FDA files used to
support the direct additive use may not
always be adequate to support even a
modest increase in the dietary exposure
resulting from its use as an indirect food
additive.
Some direct food additives have been
regulated for uses in which only a
narrow margin exists between the
cumulative estimated dietary exposure
and the acceptable dietary exposure.
Many other direct additives have been
regulated for uses for which, initially,
the margin between the estimated daily
intake and the ADI was reasonably
broad, but as the substance has been
subsequently regulated for other uses,
the margin has become quite narrow.
Because existing safety data may not be
adequate to support the use of direct
additives as components of food-contact
articles in all cases, such uses must be
evaluated on a case by case basis, either
as the subject of a food additive petition

(if the dietary exposure is likely to be
greater than 1 percent of the ADI) or as
a request for an exemption from
regulation (if the dietary exposure is
likely to be below the 1-percent ADI
threshold of regulatory concern).
Another agency concern with the
recommended approach is that some of
the direct food additives may also have
been regulated at a time when FDA did
not conduct reviews on the possible
environmental effects resulting from
such uses. (FDA regulations for
considering the environmental effect of
its actions in accordance with the
National Environmental Policy Act
(NEPA) were established on March 15,
1973.) It may be possible that the
manufacture, use, and disposal of foodcontact articles containing regulated
direct food additives may have an
adverse impact on the environment.
Therefore, the potential environmental
effects resulting from the intended use
of a direct food additive in a foodcontact article need to be evaluated by
FDA either as part of a review of a
petition or as part of a review of an
exemption from regulation request.
Further discussion of this issue is found
later in this final rule in the agency’s
response to comments 28 and 29.
For the reasons listed above, FDA has
concluded that the use of a regulated
direct food additive in a food-contact
article should either be the subject of a
specific food additive regulation
authorizing such use or be exempted
from regulation as a food additive by
FDA under the procedures specified in
this final rule. Application of the Food
Additive Definition
12. Two comments expressed the
opinion that the Monsanto decision
gives FDA the flexibility to consider
those substances migrating out of foodcontact articles in trivial amounts not to
be food additives. These comments
went on to say that the Delaney Clause
(section 409(c)(3)(A) of the act (21
U.S.C. 348(c)(3)(A)), which prohibits the
use of known carcinogens as food
additives, would therefore not apply.
FDA disagrees with the comments. It
is true that Monsanto stated that the
Commissioner has discretion to
implement the statutory scheme
established by the Food Additives
Amendment, and that this discretion
includes the option of declining to
define a substance as a food additive
(613 F.2d at 956). However, the court
also said that the Commissioner’s
discretion is limited (id.). The
Commissioner’s exercise of discretion
must be consistent with the statutory
scheme. He cannot exercise his
discretion to vitiate that scheme. Under
the Food Additives Amendment, a

carcinogenic additive is deemed to be
unsafe, no matter how low the exposure
to the additive or how low the risk from
the additive (see Public Citizen v.
Young, 831 F.2d 1108, 1122 (D.C. Cir.
1987), cert. denied, 485 U.S. 1006
(1988)). Given these facts, FDA has
formulated the threshold of regulation
regime to exempt substances from
regulation as food additives based on
the level of dietary exposure but has
conditioned that exemption on such
substances not having been shown to be
carcinogens. No other approach would
be consistent with the act.
13. Three comments recommended
that FDA clarify whether companies can
make their own threshold of regulation
determinations. The comments stated
that, in those cases where the use of the
substance meets the definition of a
‘‘food additive’’ in section 201(s) of the
act (21 U.S.C. 321(s)), individual
manufacturers should be able to make
their own determination as to whether
the use of a substance in a food-contact
article meets the criteria for an
exemption from regulation. One of the
comments requested that the agency’s
position on this issue be explicitly
stated in the final regulations.
According to Monsanto, only the
Commissioner has the statutory
authority to exempt a substance from
regulation as a food additive. A
substance that meets the definition of a
food additive in section 201(s) of the act
must, therefore, either be the subject of
a regulation authorizing its use or be
exempted from regulation by FDA under
the process specified in new § 170.39,
unless the use of the substance
conforms to an exemption for
investigational use issued under section
409(i) of the act.
From a policy standpoint, the
procedure outlined in this final rule,
whereby FDA makes all exemption
decisions, offers a number of advantages
over an approach that allows individual
manufacturers to make their own
threshold of regulation decisions. One
advantage is that the agency’s
determination as to whether a substance
used in a food-contact article meets the
criteria for an exemption from
regulation as a food additive will be
binding on the agency. Thus,
manufacturers of food-contact articles
will be able to rely on these
determinations and market their
products without fear of regulatory
action.
This approach also will result in more
consistent decisions. Qualified experts
may disagree on what specific
assumptions are appropriate for
estimating the dietary concentrations
resulting from the use of substances in

Federal Register / Vol. 60, No. 136 / Monday, July 17, 1995 / Rules and Regulations
food-contact articles. Thus, allowing
individual manufacturers to make their
own determinations would increase the
likelihood of inconsistent decisions.
For example, 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 validated
detection limit of the method used to
analyze for the substance would need to
be considered in order to estimate the
dietary concentration from the intended
use. Qualified experts may disagree not
only on the specific numeric value for
this detection limit but also on what
percentage of the detection limit should
be used in such situations to estimate
actual migration (e.g., 100 percent
versus 50 percent). Qualified experts
may also disagree on the appropriate
consumption factor to use in estimating
dietary concentrations. Different
conclusions on the environmental
effects resulting from the use of a foodcontact article may also arise from such
independent determinations. The
agency believes that having all such
exemption decisions made by a review
team consisting of a small number of
agency personnel will help lessen the
likelihood of inconsistent decisions on
these matters.
Having such determinations made by
FDA will also mean that the agency will
have more complete information on
what materials industry is actually
using in food-contact articles. As a
result, FDA will be able to make more
informed decisions in the event that
data become available that raise
significant concerns about whether the
continued use of a component of a foodcontact article is safe.
Although only the Commissioner of
FDA has the statutory authority to
exempt a substance from regulation as a
food additive in those cases where the
use of the substance meets the ‘‘food
additive’’ definition in section 201(s) of
the act, FDA emphasizes that nothing in
this final rule limits the use of a
substance exempted by FDA from
regulation to only the manufacturer who
submitted the request for an exemption.
Other manufacturers may use exempted
substances in food-contact articles as
long as the conditions of use (e.g., use
levels, temperature, type of food
contacted, etc.) are those for which the
exemption was issued.
Consistent with this fact, FDA plans
to give general notice by means of the
Federal Register, should it ever decide
to revoke an exemption. The notice will
state that continued use of such a
substance would constitute the use of an
unapproved food additive, unless a

petition is filed, and the substance is
listed for use in FDA’s regulations. It
will also set out the reasons for FDA’s
decision to revoke the exemption,
thereby providing manufacturers with
the opportunity to submit relevant data
to the agency and to request that the
exemption be reinstated.
FDA does not believe, however, that
it would be practical to routinely
provide notice in the Federal Register of
its intent to revoke an exemption. Such
a process would only unduly delay and
burden the revocation process. It would
be inconsistent with the intent of the
threshold of regulation process to
minimize the use of agency and
industry resources for those substances
whose use in food-contact articles poses
only negligible safety concerns.
Accordingly, FDA is revising § 170.39(g)
to make clear that the agency plans to
provide notice in the Federal Register
after it has decided to revoke an
exemption issued for a specific use of a
substance in a food contact article.
FDA has decided, however, not to
include in § 170.39 a statement that only
the Commissioner can make threshold
of regulation determinations. It is not
the agency’s usual practice to enumerate
in its regulations those regulatory
decisions that are reserved to the
agency. Therefore, the agency is not
doing so here.
Scope of the Exemption
14. Two comments recommended that
FDA expand its proposed threshold of
regulation to enable the agency to
exempt entire classes of compounds.
Under the scheme suggested by these
comments, FDA would review one or
more compounds within a given class,
and, if it determined that these
individual chemicals qualified for an
exemption, the agency would exempt all
of the chemicals within the class. One
of these comments expressed the view
that many manufacturers do not use
their proprietary chemicals for foodcontact applications because of FDA’s
requirement that they be regulated
based on their chemical identity, and
that the use of such an approach would
remove impediments that stifle
innovation in the food industry.
FDA disagrees with this approach for
a number of reasons. Because the level
of migration, and resulting dietary
concentration, of the chemical depend
on both its molecular weight and
chemical properties, it would be
impossible to predict whether the use of
all compounds within a class would
result in dietary concentrations below
the threshold based on the migration
properties of just one or two sample
chemicals. For example, polymeric

36587

materials manufactured from the same
monomer but having significantly
different molecular weights would
belong to the same class of chemicals
but would be expected to have different
migration properties. Similarly, the
intrinsic toxic potencies for chemicals
within a certain class may vary
significantly. For example, the
polychlorinated dibenzo-p-dioxins are a
class of 75 congeners that exhibits a
wide range of toxicity depending on the
degree of chlorination and the location
of the chlorine atoms within the
chemical structure. As a result, the
likelihood that a substance poses a
health hazard is not necessarily
determinable based on the information
about the toxicity of other chemicals
that are in the same class. In addition,
it would be difficult to predict the
environmental impact that would result
from the manufacture, use, and disposal
of all substances within a class based on
the impact of one or two chemicals.
Therefore, FDA does not believe that it
is possible, based on the review of one
or more compounds within a given
class, to justify an exemption for all
other chemicals belonging to the same
class.
For the foregoing reasons and because
the dietary concentration of a specific
chemical is dependent on the
conditions of its use (e.g., type of use,
temperature, food type, and contact
time), FDA concludes that to adequately
safeguard the public health, it is
necessary to limit exemptions under
§ 170.39 to those conditions of use of a
chemical that it has evaluated.
15. One comment recommended that
rather than require a submission for
each chemical and each proposed use,
FDA should publish guidelines based
on categories of uses that would provide
performance standards that could be
used by manufacturers to guide
customers on how to stay below the
threshold exposure.
As discussed earlier, the dietary
concentration resulting from the use of
a substance in a food-contact article may
vary considerably depending on the
type of use and the conditions of use.
Therefore, it would not be feasible to
establish guidelines for use with respect
to all possible food-contact articles
under all possible conditions.
Interpretation of such complicated
guidelines by individual manufacturers
and customers would inevitably lead to
confusion and inconsistencies.
The process specified in this final
rule, as part of which a small team of
agency personnel will review each
request for an exemption, will result in
more consistent decisions. Having all
such determinations made by FDA

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using the process specified in the final
rule should also result in the agency
having more complete information on
what substances are being used in foodcontact articles. This information will
permit the agency to take action in the
event that data become available that
raise significant questions as to whether
the continued use of a substance in a
food-contact article is safe.
16. One comment stated that the 0.5
ppb threshold was too low for the use
of pigments in food-contact articles
because such pigments are less toxic
than other chemicals. Because these
pigments are relatively insoluble, they
would also have lower bioavailability.
FDA does not believe that it is feasible
to establish specific thresholds of
regulation for each of the many types of
chemicals used in food-contact articles.
Such an approach, with many different
thresholds, would be cumbersome.
Moreover, as discussed in a previous
comment, the toxicological properties of
chemicals within a class can vary
greatly. Therefore, it would be
extremely difficult to establish a single
threshold for all the chemicals within a
given class. Because of this difficulty,
FDA is not taking any action in response
to this comment.
The agency believes that it may be
feasible in the future to establish a
higher threshold based on a substance’s
toxicological properties rather than
based on its type or on the class of
chemicals to which it belongs. For
example, as discussed in a previous
comment, it may be possible in the
future to establish separate thresholds
for substances that either have been
shown to be noncarcinogenic by
appropriate 2-year bioassays or, based
on the results of short-term toxicity
testing (e.g., mutagenicity and acute oral
feeding studies), are likely to have a low
carcinogenic potency if they are, in fact,
carcinogenic.
17. One comment requested that FDA
specifically address whether biocides
would be eligible for consideration
under the threshold of regulation
regime. Because such substances must
be registered with the Environmental
Protection Agency (EPA) in accordance
with the Federal Insecticide, Fungicide
and Rodenticide Act (FIFRA) (7 U.S.C.
136 et al.), and must undergo an
extensive review for safety and efficacy,
the comment stated that biocides are
well suited for an abbreviated review
under FDA’s threshold of regulation
process.
As long as the criteria specified in this
final rule are met, FDA will grant
exemptions from regulation as food
additives for biocides that become
components of food-contact articles.

18. Two comments requested that
FDA clarify how the presence of a
‘‘barrier’’ (one that would limit the
migration of a packaging substance into
food) would be factored into threshold
of regulation decisions. In particular,
the comment asked whether, in cases
where there is a functional barrier, and
no migration can be detected, FDA
would still consider the validated
detection limit of the method used to
analyze for the substance in its dietary
exposure estimate.
The key factor in FDA’s decision to
grant an exemption from regulation for
a substance used in a food-contact
article is whether the dietary
concentration of the substance resulting
from its use is below the threshold.
Thus, if the presence of a functional
barrier limits the migration of the
substance into food such that the
resulting dietary concentration is below
the threshold, FDA will grant an
exemption for the intended use of that
substance, provided that the other
criteria specified in this final rule are
met.
In most cases, the effectiveness of a
material to act as a barrier to migration
will depend not only on the physical
and chemical properties of the barrier
material and the potential migrant but
also on the thickness of the barrier layer
and the conditions of use (e.g.,
temperature, food type, contact time).
Therefore, it is usually not possible to
draw any conclusions regarding the
effectiveness of a barrier material in the
absence of migration data. In such cases,
requests for exemptions from the food
additive regulations would need to
contain data showing that the barrier
material precludes all but minimal
migration of the substance into food
(i.e., the resulting dietary concentration
is at or below the threshold). FDA will
consider the validated detection limit of
the method used to analyze for the
substance in arriving at its dietary
exposure estimate.
There are a number of specific
situations, however, where FDA would
not require data to show that a barrier
material precludes all but minimal
migration of the substance into food. For
example, some packaging materials such
as aluminum foil, when used as the
inner layer of laminates, have been
generally recognized as being able to
provide an effective barrier to migration
of the outer layer components into food
under a variety of conditions. In such
cases, it would not be necessary for the
requestor to carry out and submit
extraction studies designed to show the
effectiveness of the barrier layer.
Another example involves those cases
in which FDA has reviewed the barrier

material and has established specific
conditions under which the material
would indeed function as a barrier. In
these cases, the agency will be able to
make decisions on similar constructions
in the absence of any additional
extraction studies, as long as the
conditions of use do not differ
significantly from those the agency
reviewed.
19. One comment inquired as to
whether the final rule establishing a
threshold of regulation for substances
used in food-contact articles will be
applicable to regulated direct animal
feed additives that are intended to be
used as components of articles that may
contact animal feed (i.e., indirect animal
feed additives).
This final rule will allow those
substances exempted under § 170.39 to
be used in articles contacting animal
feed as long as the intended conditions
of use of the substance are those for
which the exemption was issued. This
result follows from §§ 174.6 and
§ 570.14 (21 CFR 570.14) of FDA’s
regulations. Under § 174.6 Threshold of
regulation for substances used in foodcontact articles, FDA will exempt
substances from regulation as food
additives whose use in food-contact
articles meet the criteria in § 170.39.
Authority to use substances exempted
under § 174.6 in articles contacting
animal feed is set out in § 570.14
Indirect food additives resulting from
packaging materials for animal feed and
pet food, which states that the
regulations providing for the use of
food-packaging materials in parts 174
through 179 (21 CFR parts 174 through
179) are applicable to packaging
materials used in animal feed and pet
food.
Moreover, in cases where the
exemption request concerns the use of
a substance in an article that is used
only in contact with animal feed, the
criteria used by FDA to determine
whether an exemption from regulation
is warranted will be those specified in
new § 170.39. Because § 570.14 contains
a cross-reference that includes § 174.6,
in accordance with that provision, FDA
can review a request for exemption of a
substance used only in contact with
animal feed under § 170.39.
Sections 170.39, 174.6, and 570.14,
however, will not provide for the use in
articles contacting animal feed, at a
level that is 1 percent or less of their
ADI, of substances that are currently
regulated for direct use in animal feed
in part 573 (21 CFR part 573). To
provide for such a review, FDA will
have to adopt a regulation similar to
§ 170.39 that applies to direct animal
feed additives that have not been

Federal Register / Vol. 60, No. 136 / Monday, July 17, 1995 / Rules and Regulations
regulated for direct addition to human
food. However, such a regulation is
outside the scope of this rulemaking and
would require a separate proceeding.
Application of the Exemption
20. One comment inquired whether
exempted substances may be used in
contact with all types of food.
Because the dietary concentration
resulting from the use of a substance in
a food-contact article is dependent on
the type of food with which it comes in
contact, the use of a substance in an
article contacting one type of food may
result in a dietary concentration below
the threshold, while the use of the same
material in contact with another type of
food may not. Therefore, FDA will limit
exemptions to those conditions of use
warranted by the available data.
B. The Regulation
21. One comment recommended that
FDA revise the language in
§ 170.39(a)(1) to make clear whether the
phrase ‘‘there is no reason, based on the
chemical structure of the substance, to
suspect that the substance is a
carcinogen’’ refers to impurities within
the substance or the substance itself.
FDA agrees with this comment and is
revising proposed § 170.39(a)(1) to make
it clear that the phrase ‘‘there is no
reason, based on the chemical structure
of the substance, to suspect that the
substance is a carcinogen’’ refers only to
the substance itself.
22. One comment recommended that
FDA revise the language in proposed
§ 170.39(c)(1) to make clear that the
description of the chemical composition
of the substance for which the request
is made should include, whenever
possible, the name of the chemical in
accordance with current chemical
abstracts service (CAS) nomenclature
guidelines and a CAS registry number if
available.
FDA agrees with this comment and
has revised proposed § 170.39(c)(1)
accordingly.
23. One comment recommended that
the word ‘‘substance’’ in proposed
§ 170.39(c)(4)(ii) and (c)(4)(iii) should
refer to the singular case for
consistency.
FDA agrees and has made the changes
that respond to this comment in this
final rule.
24. One comment recommended that
the regulation define in detail the types
of information required by FDA in
submissions requesting exemptions
from the food additive regulations.
FDA agrees that a detailed description
of the information that needs to be
included in a request for an exemption
should be readily available to interested

parties. However, FDA does not believe
that it is necessary or appropriate to
include this information in the Code of
Federal Regulations (CFR). The agency
considers it appropriate to make this
information available in a manner
similar to that which FDA uses with
respect to the contents of food additive
petitions. For food additive petitions,
FDA generally describes the information
that must be submitted in part 171 (21
CFR part 171) of its regulations and
maintains more detailed guidelines that
are available from the agency upon
request. While FDA publishes
modifications in the CFR only annually,
it can modify guidelines whenever
necessary, thereby providing requestors
with up-to-date guidance. This
flexibility in modifying detailed
guidelines is needed to take into
account ongoing advances in the
development of food-contact articles
and in the methodologies used to
quantify migration of components of
such articles into food.
Therefore, FDA is adding § 170.39(h),
which states that guidelines to assist
requestors in the preparation of
submissions seeking exemptions from
the food additive regulations are
available from FDA’s Office of
Premarket Approval (HFS–200), 200 C
St. SW., Washington, DC 20204.
Because it is not practical to provide
guidelines that would cover all of the
possible topics associated with these
types of submissions, this final rule
encourages interested parties to obtain
specific guidance from FDA on the
protocols to use in obtaining extraction
data, on the validation of the analytical
methods used to quantify migration
levels, on the procedures to use to relate
migration data to dietary exposures, and
on any other issue not specifically
covered in FDA’s guidelines.
FDA formerly proposed to announce
the availability of guidelines in
§ 170.39(c)(4)(v) because the guidelines
were meant to focus on questions
associated with the dietary
concentration resulting from the
intended use of a substance in a foodcontact article. However, the agency
believes it is more appropriate to
include such language as part of
§ 170.39(h) to emphasize that interested
parties may seek guidance on any issue
involving exemption requests.
Therefore, FDA is revising § 170.39 to
include this provision and has deleted
proposed § 170.39(c)(4)(v).
C. Procedural Issues
Obtaining an Exemption
25. One comment commended FDA
for its statement in the preamble that

36589

manufacturers may make their own
determination as to whether the use of
a substance in a food-contact article
meets the ‘‘food additive’’ definition in
section 201(s) of the act and
recommended that FDA explicitly state
this fact in the final regulation.
In response to this comment, FDA
would like to reaffirm its position that
nothing in the regulatory scheme
presented in this rule would prevent a
company from making its own
determination that a particular use of a
substance does not meet the definition
of a ‘‘food additive’’ in section 201(s) of
the act. However, as noted in the
proposal, companies make such
determinations at their own risk. If the
agency learns of the use of a substance
from, for example, a competitor and
reaches a different conclusion than the
company, the agency may take
regulatory action against the substance
as an unsafe food additive or against the
company that makes the substance for
introducing an adulterated food into
interstate commerce. Therefore, in cases
where it is not clear whether the use of
a food-contact article meets the ‘‘food
additive’’ definition, FDA recommends
that manufacturers seek a determination
under the procedures specified in this
rule to avoid the possibility of
regulatory action.
FDA does not believe, however, that
it is appropriate to address this issue in
the regulation. The issue raised by the
comment applies generally to FDA’s
application of the ‘‘food additive’’
definition in section 201(s) of the act.
This rulemaking concerns only the
threshold of regulation process.
Therefore, the question of whether, and
how, to incorporate into FDA’s
regulations the statement that the
comment seeks is outside the scope of
this rulemaking.
26. Seven comments recommended
that the agency establish a time limit for
reviewing and responding to requests
for exemptions from regulation as food
additives to ensure timely responses.
Two of the comments suggested specific
time limits of 60 and 90 days.
The agency agrees that such reviews
should be carried out in a timely
manner. Timely review will mean that
manufacturers and suppliers of
substances that are exempted from
regulation as food additives will be able
to market their products much more
quickly than has been the case. Timely
review will also mean that
manufacturers and suppliers of
substances that are not exempted will
receive prompt notice of the need to file
a food additive petition.
A pilot study carried out by FDA
showed that such reviews can usually

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Federal Register / Vol. 60, No. 136 / Monday, July 17, 1995 / Rules and Regulations

be completed within 3 to 4 months as
compared to the 1 to 2 years typically
required for indirect food additive
petitions. The agency is concerned,
however, that establishing a formal time
limit for completion of such reviews
will unduly restrict its ability to allocate
its limited resources to projects that may
be more critical. Therefore, the agency
has decided not to establish a time limit
for reviewing and responding to
requests for exemptions from regulation
as food additives at this time. As the
agency gains experience with its
threshold of regulation policy, it will
consider establishing an appropriate
time limit. In the interim, however, the
agency is committed to reviewing
exemption requests as expeditiously as
resources allow.
27. One comment recommended that
there be a phase-in process that would
allow companies to carefully evaluate
products that are on the market and to
obtain exemption determinations where,
and if, required.
As discussed previously, if the use of
a substance results in, or is reasonably
expected to result in, migration into
food, even at low levels, and is not
specifically excluded from the
definition of a ‘‘food additive’’ in
section 201(s) of the act, then the
substance is a food additive that must
either be the subject of a regulation
authorizing its use or be exempted from
regulation by FDA under the process
specified in this rule. However, if the
use of a substance in a food-contact
article currently on the market involves
low levels of migration into food (i.e.,
results in a dietary concentration at or
below the threshold of regulatory
concern), and is the subject of a request
for an exemption under the process
specified by this final rule, it is unlikely
that FDA would take regulatory action
during the time needed by the agency to
complete its review. Therefore, the
agency does not believe it is necessary
to establish a phase-in program to allow
companies to evaluate food-contact
articles currently on the market.
28. One comment recommended that
§ 170.39 be revised to include an
abbreviated review (i.e., one that does
not require a review of environmental
impact data and toxicological feeding
study data) for those exemption requests
that deal only with new uses of
regulated indirect food additives that
involve the same manufacturing process
but a different technical effect (e.g., a
substance currently regulated as a
defoamer in the manufacture of paper
and paperboard under § 176.170 that is
the subject of an exemption request for
its use as a deposit control agent in the
manufacture of paper and paperboard).

The agency is currently reevaluating
its environmental regulations under
NEPA, and is committed to expanding
the list of categorical exclusions found
in § 25.24 (21 CFR 25.24). However, as
indicated earlier, a key factor in FDA’s
decision to grant an exemption from
regulation is whether the substance has
a significant impact on the environment.
A new use of a regulated indirect food
additive that involves the same
manufacturing process but a different
technical effect may have, as a result of
its use or subsequent disposal, a
significantly different environmental
exposure than any previously regulated
use of the substance. Therefore, an
abbreviated review (i.e., one that does
not include a review of environmental
impact data) is not justified for all such
substances. Although these types of uses
do not currently qualify for a categorical
exclusion, some may qualify in the
future (the categorical exclusion list is
currently under consideration for
expansion).
In regard to reducing the requirements
for the submission of toxicological
feeding studies, FDA emphasizes that
§ 170.39 requires only that submissions
contain the results of an analysis of
existing toxicological information on the
substance and its impurities. This
information 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. FDA also requires this type of
information to enable it to determine
whether any of the impurities present in
the substance have been shown to be
carcinogenic, and, if carcinogenic,
whether their TD50 value is greater than
6.25 mg/kg bodyweight per day (see
§ 170.39(a)(1)). To clarify this issue,
FDA is revising the language in
§ 170.39(c)(5) to state that the only
toxicological information that must be
included in a submission for an
exemption from the food additive
regulations is an analysis of existing
toxicological information on the
substance and its impurities.
29. Two comments stated that
exempted substances should not be
subjected to the environmental impact
reviews typically required for food
additives. The comments asserted that,
instead, exempted substances should
come under a newly created
‘‘categorical exclusion’’ that would
exclude such actions from the
requirement that an environmental
assessment be prepared.
An FDA decision to exempt a
substance from regulation as a food
additive is an agency action under the
National Environmental Policy Act

(NEPA) (42 U.S.C. 4321). Under NEPA,
an agency action must include a
consideration of the environmental
effects resulting from the intended use,
unless it is the subject of one of the
categorical exclusions listed in 21 CFR
25.24. Actions are made subject to an
exclusion either because, as a class, they
will not result in the production or
distribution of any substance and,
therefore, will not result in the
introduction of any substance into the
environment, or because they meet
specific criteria that are intended to
ensure they will not cause significant
environmental effects. As stated above,
the agency is actively examining its
categorical exclusion regulations.
However, neither of the subject
comments provided information to
show that as a class, substances used in
food-contact articles would not be
introduced into the environment or to
support the establishment of a new
categorical exclusion. The agency
welcomes the submission of data and
information that would support the
establishment of a categorical exclusion
for these substances. At this time,
however, all requests for threshold of
regulation exemptions must include an
abbreviated environmental assessment.
Availability of the Information
Submitted
30. Six comments were submitted on
the general subject of what types of
information contained in submissions
under § 170.39 should be made publicly
available (i.e., on display at the Dockets
Management Branch or released in
response to requests submitted under
the Freedom of Information Act (FOIA)
(5 U.S.C. 552)). Three of these
comments were quite general,
recommending that FDA handle the
confidential information contained in
such submissions in the same manner
that it has traditionally treated other
documents submitted. A more specific
comment recommended that the
information released under FOIA
should be consistent with that released
from food additive petitions. One
comment expressed the opposite
viewpoint, stating that exempted
substances should not be considered
food additives, and that, therefore, the
rules governing the release of
information submitted on food additives
should not apply. This comment also
requested that the final regulation
include a statement recognizing the
possible trade secret status of
information submitted in support of an
exemption request. Another comment
stated that the names of companies
receiving exemption letters are trade
secret.

Federal Register / Vol. 60, No. 136 / Monday, July 17, 1995 / Rules and Regulations
As a general matter, the FOIA requires
that agencies make the fullest possible
disclosure of records to the public. The
procedures that FDA uses to handle the
release of public information in
accordance with FOIA are described in
part 20 (21 CFR part 20). Under these
procedures, information submitted to
FDA, including that submitted on the
use of food additives, is made publicly
available to the greatest extent possible.
As for substances that become
components of food below the threshold
that FDA is establishing, they will be
exempt from the requirement that their
use be the subject of a food additive
listing regulation. This exemption, like
a listing regulation, allows these
substances to be used in food contact
articles. Given the similarity in effect
between a food additive listing and the
grant of an exemption, FDA concludes
that it is appropriate for it to make
publicly available under § 170.39(e) the
same type of information that is
releasable on regulated food additives.
This information includes the name of
the company that sought and received
authorization to use the substance.
In response to the request that the
final regulation include a statement
recognizing the possible trade secret
status of information submitted in
support of an exemption request, FDA is
revising § 170.39(e) to state that the
agency will respond to all FOIA
requests for information submitted
under § 170.39 in accordance with part
20. Thus, data and information that are
trade secret or confidential commercial
or financial information are not
available for public disclosure in
accordance with § 20.61(c).
31. One comment stated that
information contained in submissions
under § 170.39 should not be released in
response to FOIA requests.
FDA does not agree with this
comment. As discussed in the previous
comment, FOIA requires that agencies
make the fullest possible disclosure of
records to the public. The agency,
however, recognizes that it has an
obligation to protect trade secret and
confidential commercial or financial
information as defined in § 20.61(a) and
(b). Therefore, FDA will not disclose
this type of information.
32. Two comments stated that the
chemical identities of exempted
substances should not be publicly
disclosed. One of these comments stated
that such information is trade secret and
considered by economists as
‘‘circumstantially relevant business
information.’’ The comment stated that,
if the company requesting an exemption
regards this information as trade secret,
keeping such information confidential is

consistent with controlling case law
interpretation of the confidentiality
standard that is applied to FDA under
Critical Mass Energy Project v. NRC, 975
F. 2d 871 (D.C. Cir. 1992). This
comment also stated that, because these
substances are exempt from regulation
as food additives, FDA is not under any
obligation to disclose their chemical
identities. The comment stated that
release of proprietary information could
force companies to make their own
determinations as to whether a food
additive regulation is needed. This
comment suggested that FDA adopt a
system whereby the chemical would be
identified only by the general class of
chemicals to which it belongs. This
comment also pointed out that EPA has
used this type of system in PreManufacture Notifications submitted
under the Toxic Substances Control Act
(40 CFR 720.85). One of these comments
raised the possibility that exempted
substances could be referred to only by
their trade names.
FDA disagrees with the suggestion
that exempted substances be referred to
only by trade names or by reference to
the general class of chemicals to which
they belong. Two factors underlie FDA’s
disagreement. First, the provisions of
the act added by the 1958 Food
Additives Amendment permit any
manufacturer to use any regulated food
additive as long as the substance meets
all applicable specifications, including
those associated with the identity of the
additive. Second, as previously
discussed, FOIA requires that agencies
make the fullest possible disclosure of
records to the public. Under the
procedures used by FDA to determine
the releasability of information under
FOIA, the agency has traditionally
considered the chemical identity of food
additives to be disclosable information,
and thus, the regulations implementing
the 1958 Food Additives Amendment
refer to food additives by their chemical
names. Because FDA’s approach to
exempted substances derives from the
food additive provisions of the act, and,
as stated above, FDA is acquiescing in
the use of the substance, FDA concludes
that the chemical identities of exempted
substances are disclosable under FOIA.
Critical Mass is not to the contrary.
While a company has an alternative to
making a submission to FDA under
§ 170.39 (i.e., filing a food additive
petition), and thus, the submission is in
a sense voluntary, the key question
under Critical Mass is whether the
information is of a kind that would
customarily not be released to the
public by the person from whom it was
obtained (975 F.2d at 879). As stated
above, information about the chemical

36591

identity of food additives for which
listing is sought is routinely disclosed to
the public in the Federal Register,
pursuant to section 409 of the act.
Submitters are well aware of this fact.
Thus, FDA finds no merit to the
suggestion by the comment that the
identity of substances subject to
§ 170.39 must be kept confidential. To
provide differently for substances
subject to § 170.39 would be to create a
special exemption. Clearly, Critical
Mass does not require such a result.
From a practical standpoint, chemical
nomenclature has typically been used to
characterize food additives because
chemical names are universally
recognized and are not subject to change
as trade names often are. Moreover,
trade names are often used to refer to
formulations in which the chemical
composition is held confidential. In
such cases, referring to regulated food
additives by trade names would make it
impossible for other manufacturers to
determine whether their chemical
substances meet applicable regulations.
A similar situation would occur if the
list of exempted substances made
publicly available did not include the
chemical identities of such substances.
Making available the chemical
identities of substances exempted from
regulation will permit other
manufacturers to use these substances
as long as the conditions of use are no
more likely to result in migration to
food than those for which the
exemption was originally issued. It will
also allow interested persons to
determine what substances have been
exempted by FDA under the process
established by this final rule. FDA
believes that, in the interest of open
government, it is essential that decisions
made under this policy be available to
the public. Therefore, for the reasons
specified above, FDA will make
publicly available the chemical
identities of exempted substances.
33. One comment stated that the
technical effect or function of the
substance should not be made publicly
available.
Under the procedures used by FDA to
implement FOIA, the agency has not
considered information on the technical
effect or functionality of a food additive
to be trade secret as defined in § 20.61(a)
or confidential commercial or financial
information as defined in § 20.61(b).
Because the dietary exposure resulting
from the use of a substance in a foodcontact article may vary considerably
depending on the technical effect of that
additive, it is often necessary to include
such information in the regulation
authorizing a specific type of use of the
food additive in order to restrict the

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dietary exposure to levels that can be
supported by existing safety data. For
example, substances regulated in 21
CFR 178.3400 are restricted to use as
emulsifiers and/or surface active agents
in the manufacture of articles or as
components of articles contacting food.
Moreover, the provisions of the act
added by the 1958 Food Additives
Amendment permit any manufacturer to
use any regulated food additive as long
as the use of the substance meets all
applicable specifications and
limitations. Such limitations include
those that restrict the use of the additive
to a specific technical effect. Therefore,
it is often necessary to include this
information as part of the conditions of
use set forth in the regulation
authorizing the use of the additive so
that other manufacturers may use the
same substance under only those
conditions that are safe. In addition to
being made available as part of a
regulation, the agency has routinely
made technical effect information
contained in food additive petitions
available to the public in response to
FOIA requests in accordance with
§ 171.1(h)(1)(i). Consistent with the
explanation above, FDA sees no reason
to change this policy with regard to food
additives exempted from regulation.
Treatment of the List of Exempted Uses
of Substances
34. One comment recommended that
in addition to making available a list of
exemptions at the Dockets Management
Branch, FDA should publish this list in
the Federal Register.
The public should have ready access
to an up-to-date list of those uses of
substances that have been exempted
from regulation as food additives by
FDA. However, maintaining such a list,
updated on a regular basis, on display
at the Dockets Management Branch, is
the most efficient way of achieving this
result. FDA anticipates being able to
respond to exemption requests within 3
to 4 months. Thus, the list of exempted
substances would be continually
changing. Monthly updates in the
Federal Register would be expensive
and yearly updates of little value.
Therefore, FDA has no plans to publish
this list in the Federal Register.
However, to ensure that interested
persons are aware that FDA is
maintaining such a list at its Dockets
Management Branch, the agency plans
to publish annually a brief notice in the
Federal Register on the availability of
this list. An updated list of exempted
substances can also be obtained by
contacting FDA’s Office of Premarket
Approval (address above). FDA is
revising § 170.39(e) to reflect this fact.

Revocation
35. One comment recommended that
FDA establish timeframes for the
revocation process. The comment
suggested that the requestor would have
60 days to respond to FDA’s tentative
decision to revoke an exemption. Once
the response is submitted, FDA would
have 60 days to reach its final decision.
FDA agrees that in cases in which
new information becomes available
showing that continued exemption of a
substance in a food-contact article from
regulation under the food additive
provisions cannot be supported in light
of existing safety data, the requestor’s
response to FDA’s tentative decision to
revoke an exemption, and FDA’s
subsequent decision, should occur in a
timely manner. However, because the
complexity of such reviews may vary
greatly and require varying amounts of
time to complete, FDA does not
consider it to be appropriate to establish
specific timeframes for such reviews.
III. Other Actions
FDA is revising § 170.39(c) to state
that three copies of a request for an
exemption from regulation are to be
submitted. The agency is requiring three
copies to help expedite its review of
such requests. To further expedite such
reviews, the agency is revising
§ 170.39(c) to state that 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) (21 CFR 10.20(c)(2)).
IV. Analysis of Impacts
FDA has examined the impacts of this
final rule under Executive Order 12866
and the Regulatory Flexibility Act (Pub.
L. 96–354). Executive Order 12866
directs agencies to assess all costs and
benefits of available regulatory
alternatives and, when regulation is
necessary, to select regulatory
approaches that maximize net benefits
(including potential economic,
environmental, public health and safety
effects; distributive impacts; and
equity). Under Executive Order 12866, a
regulatory action is economically
significant if it meets any one of a
number of specified conditions,
including having an annual effect on the
economy of $100 million or adversely
affecting in a material way a sector of
the economy, competition, or jobs. A
regulation is otherwise considered
significant under Executive Order 12866
if it raises novel legal or policy issues.
The Regulatory Flexibility Act requires
analyzing options for regulatory relief
for small businesses. FDA finds that this

final rule is not a significant regulatory
action as defined by Executive Order
12866. In compliance with the
Regulatory Flexibility Act, the agency
certifies that this final rule will not have
a significant impact on a substantial
number of small businesses.
38. One comment suggested that the
proposed threshold of regulation
process would have an adverse impact
on small businesses. FDA disagrees. The
regulation that FDA is adopting does not
prohibit or restrict any present activity
and, therefore, does not generate
compliance costs for either large or
small firms. In addition, FDA has
received no information that the
benefits of the proposed action will
accrue differentially to large firms. In
fact, this approach should minimize the
burden on all businesses by providing a
procedure that is less burdensome than
the food additive petition process.
Without this threshold of regulation
process, those components of foodcontact materials whose use results in
low levels of migration into food would
require premarket approval through the
food additive petition process.
Based on information provided to
FDA by representatives of the food
packaging and processing industries, the
collection of information and
preparation of an exemption request for
review under the process established by
this final rule is estimated to cost
anywhere from $1,400 to $25,000
depending on the complexity of the
project. If analytical studies are required
to be carried out to show that the dietary
exposure resulting from the proposed
use is below the threshold of regulation,
FDA estimates that the additional cost
would vary from $10,000 to $50,000
depending on the complexity of the
project (e.g., the number of substances
or food simulating solvents involved,
and the method of analysis). Thus, the
agency estimates that the total cost to
submit exemption from regulation
requests may vary from $1,400 to
$75,000.
The time required to prepare such
requests would also vary with the type
of data needed to estimate the dietary
exposure associated with the intended
use. A simple request (i.e., one that does
not contain any analytical work) would
typically contain: (1) Identity and use
information; (2) a literature search of the
existing toxicological data on the
substance and its impurities; and (3)
information on the environmental
impact resulting from the proposed use
of the substance. Based on information
provided to FDA by representatives of
the food packaging and processing
industries, the average time to prepare
such requests is estimated to be 68

Federal Register / Vol. 60, No. 136 / Monday, July 17, 1995 / Rules and Regulations
hours. The average time to prepare
requests that include analytical work
(e.g., extraction studies carried out using
food-simulating solvents, analytical
studies to determine the residual level
of the substance in the food-contact
article) is estimated to be 108 hours.
Although the preparation of requests
for exemptions from regulation may cost
anywhere from $1,400 to $75,000 and
require on average 68 hours to complete
(108 hours for submissions requiring
analytical data), these estimates
demonstrate that there will be a
significant decrease in the overall
burden to businesses for those
components of food-contact articles that
are exempted from regulation by this
expedited process but that previously
would have required premarket
approval via the food additive petition
process. (Petitions on these types of
issues can require on average 2,600
hours to prepare and cost anywhere
from $85,000 to $100,000.) Whenever
possible, FDA will provide assistance to
requestors to minimize the likelihood
that unnecessary work will be
performed. Based on the preceding
considerations, FDA finds that the
proposed action will not have an
adverse impact on small businesses.
In summary, the comments do not
provide a basis on which to change the
conclusions of the economic analysis
prepared for the proposed rule or to
establish that another option would
provide higher net benefits.
V. Environmental Impact
Considerations
The agency has previously reviewed
the environmental effects of this rule as
announced in the proposal (see 58 FR
52719, October 12, 1993). The agency
determined under 21 CFR 25.24(a)(8)
that neither an environmental
assessment nor an environment impact
statement is required. No new
information or comments have been
received that would affect the agency’s
previous determination.
The agency is required to consider the
environmental impact of each action to
exempt a component of a food-contact
article from regulation as a food
additive. The final rule sets out the type
of information that FDA needs to
determine the impact on the
environment resulting from the
intended use. The agency’s finding of no
significant impact, and the evidence
supporting that finding, contained in an
environmental assessment, will be made
available for public inspection at the
Dockets Management Branch (address
above) for those substances whose use
in food-contact articles has been

exempted from regulation by the
process established by this rule.
VI. Paperwork Reduction Act
Section 170.39 of this final rule
contains information collection
requirements that were submitted for
review and approval to the Office of
Management and Budget (OMB), as
required by section 3504(h) of the
Paperwork Reduction Act of 1980. The
requirements were approved and
assigned OMB control number 0910–
0298.
VII. Conclusions
Although a number of comments
expressed the opinion that the 0.5 ppb
threshold is more conservative and
restrictive than is necessary to
adequately protect the public health, no
data were submitted that would justify
FDA establishing a threshold of
regulatory concern at a dietary
concentration level higher than 0.5 ppb.
Based on its analysis of the available
evidence, FDA concludes that this
evidence does not support a threshold
significantly higher than 0.5 ppb,
especially where the substance being
considered for an exemption has not
been the subject of any toxicological
testing. Therefore, this final rule
establishes 0.5 ppb as the threshold of
regulatory concern for substances
intended for use in food-contact articles.
This final rule also establishes the
threshold of regulatory concern for
regulated direct food additives used in
food-contact articles as that dietary
exposure that is at or below 1 percent
of the ADI for that substance.
Listed below are the revisions that are
being incorporated into this final rule
based on comments received in
response to the proposal:
(1) FDA is revising § 170.39(a)(1) to
make it clear that the phrase ‘‘there is
no reason, based on the chemical
structure of the substance, to suspect
that the substance is a carcinogen’’
refers only to the substance itself (see
comment 21 of this document).
(2) FDA is revising § 170.39(a)(2)(ii) to
state that, for requests seeking an
exemption on the basis that the
substance is a regulated direct food
additive whose use in a food-contact
article will result in a dietary exposure
at or below 1 percent of the ADI for that
substance, FDA’s review will not
necessarily be restricted to ADI values
based on data in FDA files. In particular,
in cases where FDA has not calculated
an ADI value for a regulated direct food
additive, the agency will consider ADI
values from other appropriate sources
(see comment 9 of this document).

36593

(3) FDA is adding paragraph (h) to
§ 170.39 to state that guidelines to assist
requestors in the preparation of
submissions seeking exemptions from
the food additive regulations are
available from FDA’s Office of
Premarket Approval (HFS–200, 200 C
St. SW., Washington, DC 20204).
Because it is not practical to provide
guidelines that would cover all of the
possible topics associated with these
types of submissions, § 170.39(h)
encourages interested parties to obtain
specific guidance from FDA on the
appropriate protocols to be used for
obtaining extraction 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 FDA’s
guidelines (see comment 24 of this
document).
(4) FDA is revising § 170.39(c)(1) to
state that the description of the
chemical composition of the substance
for which the request is made should
include, whenever possible, the name of
the chemical in accordance with current
CAS nomenclature guidelines and a
CAS registry number, if available (see
comment 22 of this document).
(5) For consistency, FDA is revising
§ 170.39(c)(4)(ii) and (c)(4)(iii) so that
the word ‘‘substance’’ refers to the
singular case (see comment 23 of this
document).
(6) FDA is revising the language in
§ 170.39(c)(5) to state that the only
toxicological information that must be
included in a submission for an
exemption from the food additive
regulations is an analysis of existing
toxicological data on the substance and
its impurities. This information 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 value is greater than
6.25 mg/kg bodyweight per day in
accordance with § 170.39(a)(1) (see
comment 28 of this document).
(7) FDA is revising § 170.39(e) to state
that interested persons may obtain a list
of exempted substances by contacting
FDA’s Office of Premarket Approval
(HFS–200), 200 C St. SW., Washington,
DC 20204 (see comment 34 of this
document).
(8) FDA is also revising § 170.39(e) to
state that FDA will handle requests for
copies of releasable information
contained in submissions requesting
exemptions from the food additive

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Federal Register / Vol. 60, No. 136 / Monday, July 17, 1995 / Rules and Regulations

regulations in accordance with FDA’s
FOIA procedures as described in part
20. 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
21 CFR 20.61(c) (see comment 30 of this
document).
(9) FDA is revising the language in
§ 170.39(g) to state that the agency plans
to notify 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 (see comment
13 of this document).
(10) FDA is revising § 170.39(c) to
state that three copies of a request for an
exemption from regulation are to be
submitted. 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) (see Section III. of this
document: Other Actions). In addition
to these changes, FDA is clarifying its
definition of TD50 in § 170.39(a)(1). This
minor change from the October 12,
1993, proposal ensures the scientific
soundness of this definition.
VIII. References
The following references have been
placed on display in the Dockets
Management Branch (address above)
and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday
through Friday.
1. Rulis, A., ‘‘Threshold of Regulation:
Options for Handling Minimal Risk
Situations,’’ in Food Safety Assessment,
edited by Finley, J. W., S. F. Robinson, and
D. J. Armstrong, American Chemical Society
Symposium Series 484, pp. 132–139, 1992.
2. Rulis, A. M., D. G. Hattan, and V. M.
Morgenroth III, ‘‘FDA’s Priority Based
Assessment of Food Additives,’’ Regulatory
Toxicology and Pharmacology, vol. 4, pp.
37–56, 1984.

List of Subjects
21 CFR Part 5
Authority delegations (Government
agencies), Imports, Organization and
functions (Government agencies).
21 CFR Part 25
Environmental impact statements,
Foreign relations, Reporting and
recordkeeping requirements.

21 CFR Part 171
Administrative practice and
procedure, Food additives.
21 CFR Part 174
Food additives, Food packaging.
Therefore, under the Federal Food,
Drug, and Cosmetic Act and under
authority delegated to the Commissioner
of Food and Drugs, 21 CFR parts 5, 25,
170, 171, and 174 are amended as
follows:
PART 5—DELEGATIONS OF
AUTHORITY AND ORGANIZATION
1. The authority citation for 21 CFR
part 5 continues to read as follows:
Authority: 5 U.S.C. 504, 552, App. 2; 7
U.S.C. 138a, 2271; 15 U.S.C. 638, 1261–1282,
3701–3711a; secs. 2–12 of the Fair Packaging
and Labeling Act (15 U.S.C. 1451–1461); 21
U.S.C. 41–50, 61–63, 141–149, 467f, 679(b),
801–886, 1031–1309; secs. 201–903 of the
Federal Food, Drug, and Cosmetic Act (21
U.S.C. 321–394); 35 U.S.C. 156; secs. 301,
302, 303, 307, 310, 311, 351, 352, 354, 361,
362, 1701–1706, 2101, 2125, 2127, 2128 of
the Public Health Service Act (42 U.S.C. 241,
242, 242a, 242l, 242n, 243, 262, 263, 263b,
264, 265, 300u–300u–5, 300aa–1, 300aa–25,
300aa–27, 300aa–28); 42 U.S.C. 1395y,
3246b, 4332, 4831(a), 10007–10008; E.O.
11490, 11921, and 12591; secs. 312, 313, 314
of the National Childhood Vaccine Injury Act
of 1986, Pub. L. 99–660 (42 U.S.C. 300aa–1
note).

2. Section 5.61 is amended by adding
new paragraph (h) to read as follows:
§ 5.61 Food standards, food additives,
generally recognized as safe (GRAS)
substances, color additives, nutrient
content claims, and health claims.

*

*
*
*
*
(h) The following officials are
authorized to issue letters concerning
substances determined to be below the
‘‘threshold of regulation’’ under § 170.39
of this chapter:
(1) The Director and Deputy Directors,
Center for Food Safety and Applied
Nutrition (CFSAN).
(2) The Director, Office of Policy,
Planning and Strategic Initiatives,
CFSAN.
(3) The Director, Office of Premarket
Approval, CFSAN.
(4) The Directors of the Divisions of
Petition Control and Product Policy,
Office of Premarket Approval, CFSAN.
PART 25—ENVIRONMENTAL IMPACT
CONSIDERATIONS

21 CFR Part 170

3. The authority citation for 21 CFR
part 25 continues to read as follows:

Administrative practice and
procedure, Food additives, Reporting
and recordkeeping requirements.

Authority: Secs. 201–903 of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C.
321–393); secs. 351, 354–361 of the Public
Health Service Act (42 U.S.C. 262, 263b–

264); 42 U.S.C. 4321, 4332; 40 CFR parts
1500–1508; E.O. 11514 as amended by E.O.
11991; E.O. 12114.

4. Section 25.22 is amended by
revising paragraph (a)(10) to read as
follows:
§ 25.22 Actions requiring preparation of an
environmental assessment.

(a) * * *
(10) Approval of food and color
additive petitions, approval of requests
for exemptions for investigational use of
food additives, and granting of requests
for exemption from regulation as a food
additive.
*
*
*
*
*
5. Section 25.31a is amended by
revising the introductory text of
paragraphs (a), (b)(1), and (b)(2) to read
as follows:
§ 25.31a Environmental assessment for
proposed approvals of FDA-regulated
products—Format 1

(a) For proposed actions to approve
food or color additives, drugs, biological
products, animal drugs, and class III
medical devices, for proposed actions to
affirm food substances as generally
recognized as safe (GRAS), and for
proposed actions to grant requests for
exemption from regulation as a food
additive, the applicant or petitioner
shall prepare an environmental
assessment in the following format:
*
*
*
*
*
(b)(1) For actions (either to approve
food additive petitions or to grant
requests for exemption from regulation
as a food additive) concerning
components of food-contact articles
present in the finished food-packaging
material at a level not greater than 5percent-by-weight, the following
information is required for the format
items specified:
*
*
*
*
*
(b)(2) For actions (either to approve
food additive petitions or to grant
requests for exemption from regulation
as a food additive) concerning
components of food-contact articles to
be used in surfaces of permanent or
semipermanent equipment or of other
food-contact articles intended for
repeated use, the following information
is required for the items specified:
*
*
*
*
*
PART 170—FOOD ADDITIVES
6. The authority citation for 21 CFR
part 170 continues to read as follows:
Authority: Secs. 201, 401, 402, 408, 409,
701 of the Federal Food, Drug, and Cosmetic
Act (21 U.S.C. 321, 341, 342, 346a, 348, 371).

7. Section 170.3 is amended by
redesignating paragraph (e) as (e)(1) and

Federal Register / Vol. 60, No. 136 / Monday, July 17, 1995 / Rules and Regulations
by adding new paragraph (e)(2) to read
as follows:
§ 170.3

Definitions.

*

*
*
*
*
(e)(2) Uses of food additives not
requiring a listing regulation.
Substances used in food-contact articles
(e.g., food-packaging and foodprocessing equipment) that migrate, or
may be expected to migrate, into food at
such negligible levels that they have
been exempted from regulation as food
additives under § 170.39.
*
*
*
*
*
8. New § 170.39 is added to subpart B
to read as follows:
§ 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 foodprocessing 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 § 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 foodcontact 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 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

36595

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 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 foodcontact 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.
Depending on the type of use, this
information should be in the form of an
abbreviated environmental assessment
as specified in § 25.31a(b)(1) or (b)(2) 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), 200 C
St. SW., Washington, DC 20204.
(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

36596

Federal Register / Vol. 60, No. 136 / Monday, July 17, 1995 / Rules and Regulations

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), 200 C St. SW.,
Washington, DC 20204. The agency’s
finding of no significant impact and the
evidence supporting that finding,
contained in an environmental
assessment, also will be available for
public inspection at the Dockets
Management Branch in accordance with
§ 25.41(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) Guidelines 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), 200 C
St. SW., Washington, DC 20204.
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
guidelines.

PART 171—FOOD ADDITIVE
PETITIONS
9. The authority citation for 21 CFR
part 171 continues to read as follows:
Authority: Secs. 201, 402, 409, 701 of the
Federal Food, Drug, and Cosmetic Act (21
U.S.C. 321, 342, 348, 371).

10. New § 171.8 is added to subpart A
to read as follows:
§ 171.8 Threshold of regulation for
substances used in food-contact articles.

Substances used in food-contact
articles (e.g., food-packaging or foodprocessing equipment) that migrate or
that may be expected to migrate into
food at negligible levels may be
reviewed under § 170.39 of this chapter.
The Food and Drug Administration will
exempt substances whose uses it
determines meet the criteria in § 170.39
of this chapter from regulation as food
additives and, therefore, a food additive
petition will not be required for the
exempted use.
PART 174—INDIRECT FOOD
ADDITIVES: GENERAL
11. The authority citation for 21 CFR
part 174 continues to read as follows:
Authority: Secs. 201, 402, 409, 701 of the
Federal Food, Drug, and Cosmetic Act (21
U.S.C. 321, 342, 348, 371).

12. New § 174.6 is added to read as
follows:
§ 174.6 Threshold of regulation for
substances used in food-contact articles.

Substances used in food-contact
articles (e.g., food-packaging or foodprocessing equipment) that migrate, or
that may be expected to migrate, into
food at negligible levels may be
reviewed under § 170.39 of this chapter.
The Food and Drug Administration will
exempt substances whose uses it
determines meet the criteria in § 170.39
of this chapter from regulation as food
additives and, therefore, a food additive
petition will not be required for the
exempted use.
Dated: July 11, 1995.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 95–17435 Filed 7–14–95; 8:45 am]
BILLING CODE 4160–01–P