80 FR 14839 - Listing of Color Additives Exempt From Certification; Synthetic Iron Oxide

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 54 (March 20, 2015)

Page Range		14839-14842
FR Document		2015-06418

The Food and Drug Administration (FDA or we) is amending the color additive regulations to provide for the expanded safe use of synthetic iron oxide as a color additive to include use in soft and hard candy, mints, and chewing gum. This action is in response to a petition filed by Wm. Wrigley Jr. Company (Wrigley).

Federal Register, Volume 80 Issue 54 (Friday, March 20, 2015)

[Federal Register Volume 80, Number 54 (Friday, March 20, 2015)]
[Rules and Regulations]
[Pages 14839-14842]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2015-06418]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 73

[Docket No. FDA-2013-C-1008]

Listing of Color Additives Exempt From Certification; Synthetic
Iron Oxide

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA or we) is amending the
color additive regulations to provide for the expanded safe use of
synthetic iron oxide as a color additive to include use in soft and
hard candy, mints, and chewing gum. This action is in response to a
petition filed by Wm. Wrigley Jr. Company (Wrigley).

DATES: This rule is effective April 21, 2015. See section X for further
information on the filing of objections. Submit either electronic or
written objections and requests for a hearing by April 20, 2015.

ADDRESSES: You may submit either electronic or written objections and
requests for a hearing, identified by Docket No. FDA-2013-C-1008, by
any of the following methods:

Electronic Submissions

Submit electronic objections in the following way:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.

Written Submissions

Submit written objections in the following ways:
Mail/Hand delivery/Courier (for paper submissions):
Division of Dockets Management (HFA-305), Food and Drug Administration,
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
Instructions: All submissions received must include the Docket No.
FDA-2013-C-1008 for this rulemaking. All objections received will be
posted without change to http://www.regulations.gov, including any
personal information provided. For detailed instructions on submitting
objections, see the ``Objections'' heading of the SUPPLEMENTARY
INFORMATION section.
Docket: For access to the docket to read background documents or
objections received, go to http://www.regulations.gov and insert the
docket number, found in brackets in the heading of this document, into
the ``Search'' box and follow the prompts and/or go to the Division of
Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Laura A. Dye, Center for Food Safety
and Applied Nutrition (HFS-265), Food and Drug Administration, 5100
Paint Branch Pkwy., College Park, MD 20740-3835, 240-402-1275.

SUPPLEMENTARY INFORMATION:

I. Introduction

In a document published in the Federal Register of September 17,
2013 (78 FR 57105), we announced that we had filed a color additive
petition (CAP 3C0298) submitted by Wm. Wrigley Jr. Company, c/o
Exponent Inc., 1150 Connecticut Ave. NW., Suite 1100, Washington, DC
20036 (petitioner). The petition proposed to amend the color additive
regulations in Sec. 73.200 Synthetic Iron Oxide (21 CFR 73.200) by
expanding the safe use of synthetic iron oxide as a color additive to
include use in soft and hard candy, mints, and chewing gum. The
petitioner requested that the proposed uses be permitted at levels
consistent with current good manufacturing practice (GMP). The petition
also proposed to lower the specification limit for lead in synthetic
iron oxide for human food use from 10 milligrams per kilogram (mg/kg;
10 parts per million (ppm)) to 5 mg/kg (5 ppm).

II. Background

Currently, synthetic iron oxides and their hydrated forms are
approved as color additives for the following direct uses in human
food, drugs, and cosmetics: (1) In sausage casings intended for
consumption in an amount not exceeding 0.10 percent by weight of the
finished food (Sec. 73.200); (2) in ingested or topically-applied
drugs with a limit for ingested drugs of 5 milligrams, calculated as
elemental iron, per day for labeled or prescribed dosages (21 CFR
73.1200); and (3) in cosmetics generally, including cosmetics applied
to the area of the eye, in amounts consistent with GMP (21 CFR
73.2250).
Synthetically prepared iron oxides and their hydrated forms include
red iron oxide, yellow iron oxide, black iron oxide, and brown iron
oxide, which is

[[Page 14840]]

a blend of various iron oxides. For the subject petition, synthetic
iron oxides are intended to be used in soft and hard candy, mints, and
chewing gum in amounts consistent with GMP. The maximum GMP use level
for iron oxides depends on the color of the iron oxide and the
application. We have determined that the amount of the color additive
used in these foods is self-limiting (Ref. 1). Therefore, there is no
need for a specific upper limit on the percent by weight of iron oxide
in hard and soft candies, mints, and chewing gum in the regulation for
these foods.

III. Evaluation of Safety

Under section 721(b)(4) of the Federal Food, Drug, and Cosmetic Act
(the FD&C Act) (21 U.S.C. 379e(b)(4)), a color additive cannot be
listed for a particular use unless the data and information available
to FDA establishes that the color additive is safe for that use. FDA's
color additive regulations in 21 CFR 70.3(i) define ``safe'' to mean
that there is convincing evidence that establishes with reasonable
certainty that no harm will result from the intended use of the color
additive. To establish with reasonable certainty that a color additive
intended for use in food is not harmful under its intended conditions
of use, we consider the estimated human dietary exposure to the
additive, the additive's toxicological data, and other relevant
information (such as published literature) available to us. We compare
an individual's estimated daily intake (EDI) of the additive from all
sources to an acceptable daily intake (ADI) established by
toxicological data. The EDI is determined by projections based on the
amount of the additive proposed for use in particular foods and on data
regarding the amount consumed from all sources of the additive. We
typically use the EDI for the 90th percentile consumer of a color
additive as a measure of high chronic dietary exposure.

IV. Safety of Petitioned Use of the Additive

To support the safety of the proposed uses of synthetic iron oxide,
Wrigley provided information about iron intake expected to result from
the proposed new uses of synthetic iron oxide, as well as intake from
other sources of iron. There are many dietary sources of iron,
including from food ingredients, dietary supplements, and from food
that contains naturally occurring iron. Specifically, Wrigley submitted
detailed exposure estimates of iron that took into account the
following: (1) The proposed uses of synthetic iron oxide as a color
additive in soft and hard candy, mints, and chewing gum based on the
maximum anticipated use levels; (2) the current use of synthetic iron
oxide to color sausage casings; (3) background iron from conventional
food based on the iron content declared on food labels; (4) iron from
dietary supplements; and (5) oral exposure to iron oxides from their
use as color additives in lipstick. These exposure estimates assumed
that all of the iron that is present is absorbed in the
gastrointestinal tract. Wrigley also provided exposure estimates to
iron that took into account the bioavailability of iron from all
current dietary sources, proposed uses, and lipstick. Wrigley compared
these intake estimates to the Tolerable Upper Intake Level (UL) for
iron established by the Institute of Medicine (IOM) of the National
Academies. Based on this and other information, Wrigley concluded that
the proposed use of synthetic iron oxide to color soft and hard candy,
mints, and chewing gum is safe.

A. Estimated Daily Intake of Iron

Using food consumption data from the 2003-2008 National Health and
Nutrition Examination Survey (NHANES), Wrigley's estimated exposure to
iron from the proposed uses in soft and hard candy, mints and chewing
gum for the U.S. population (2 years of age and older) to be 16.3 mg/p/
day (d) for the 90th percentile consumer. Wrigley also provided dietary
exposure estimates to iron for children 2 to 5 years of age, children 2
to 13 years of age, and adolescents and adults 14 years of age and
older. For these population groups, Wrigley estimated the exposure to
iron from the proposed uses at the 90th percentile to be 12.2 mg/p/d,
15.6 mg/p/d, and 16.4 mg/p/d, respectively. Wrigley also estimated the
cumulative exposure to iron from all food sources (current and
proposed) for the U.S. population (2 years of age and older) to be 40.6
mg/p/d for the 90th percentile consumer. Wrigley also provided dietary
exposure estimates to iron for children 2 to 5 years of age, children 2
to 13 years of age, and adolescents and adults 14 years of age and
older. For these population groups, Wrigley estimated the exposure to
iron at the 90th percentile to be 31.2 mg/p/d, 34.6 mg/p/d, and 41.5
mg/p/d, respectively. In addition, Wrigley estimated exposure to iron
from all food sources (current and proposed) and lipstick for females
10 to 13 years old, and 14 years of age and older. The exposure at the
90th percentile for these two population groups was 33.8 mg/p/d and
40.2 mg/p/d, respectively. Wrigley noted that these exposure estimates
are conservative and assume that all of the iron present is
bioavailable. We have no further questions regarding Wrigley's exposure
estimates for iron in food and cosmetics and conclude that the
petitioner's exposure estimates are sufficiently conservative to
account for the use of iron oxides in ingested drugs (Ref. 2). We also
conclude that exposure from indirect uses of iron oxides, such as for
colorants for food-contact polymers authorized in 21 CFR 178.3297,
would not significantly contribute to the overall exposure to iron
oxides.
To address the bioavailability of iron, Wrigley provided
information showing approximately 18 percent of iron from conventional
foods and dietary supplements is bioavailable, and that about 1 percent
of iron from synthetic iron oxide is bioavailable. Based on this
information, Wrigley provided exposure estimates that take into account
the bioavailability of iron. Wrigley estimated the exposure to
bioavailable iron from the proposed uses at the 90th percentile to be
0.16 mg/p/d, 0.12 mg/p/d, 0.16 mg/p/d, and 0.16 mg/p/d for the U.S.
population (2 years of age and older), children 2 to 5 years of age,
children 2 to 13 years of age, and adolescents and adults 14 years of
age and older, respectively. Wrigley estimated the cumulative exposure
to bioavailable iron from all food sources (current and proposed) at
the 90th percentile to be 6.02 mg/p/d, 4.68 mg/p/d, 4.99 mg/p/d, and
6.21 mg/p/d for the U.S. population (2 years of age and older),
children 2 to 5 years of age, children 2 to 13 years of age, and
adolescents and adults 14 years of age and older, respectively. For
females 10 to 13 years old, and 14 years of age and older, Wrigley
estimated exposure to bioavailable iron from all food sources (current
and proposed) and lipstick to be 5.07 mg/p/d and 6.12 mg/p/d,
respectively (Ref. 2).

B. Acceptable Intake Level for Iron

In 2000, the Standing Committee on the Scientific Evaluation of
Dietary Reference Intakes of the Food and Nutrition Board at the IOM
conducted an extensive review of relevant published scientific
literature to determine dietary reference intakes and ULs for iron. The
IOM published a detailed report that included a UL for iron of 40 mg/d
for children (2 to 5 years of age and 2 to 13 years of age), and a UL
of 45 mg/d for adolescents and adults (14 years of age and older) (Ref.
3).
The IOM considers the UL as the highest daily intake level of a
nutrient that poses no risk of adverse effects when the nutrient is
consumed over

[[Page 14841]]

long periods of time. The UL is determined using a risk assessment
model developed specifically for nutrients and, generally speaking, may
consider intake from such sources as food, water, nutrient supplements,
and pharmacological agents. The dose-response assessment, which
concludes with an estimate of the UL, is built upon three toxicological
concepts commonly used in assessing the risk of exposures to chemical
substances: No-observed-adverse-effect level, lowest-observed-effect
level, and an uncertainty factor. We considered the ULs established by
the IOM relative to the intake estimates as the primary basis for
assessing the safety of iron from the proposed uses of synthetic iron
oxide. We also reviewed scientific articles on the safety of iron
submitted by Wrigley, as well as other relevant published studies
available to FDA.
The exposure estimates to iron from all food sources, including the
proposed use of synthetic iron oxide in soft and hard candy, mints, and
chewing gum, at the 90th percentile for children 2 to 5 years of age
and for children 2 to 13 years of age, without taking into account the
bioavailability of the iron, is 31.2 mg/p/d and 34.6 mg/p/d,
respectively. Both of these exposure estimates are below the UL for
these age groups. The exposure estimate to iron from all food sources
(current and proposed) and lipstick for females 10 to 13 years old at
the 90th percentile of 33.8 mg/p/d is also below the UL established for
this group. For adolescents and adults 14 years of age and older, the
exposure estimate for iron at the 90th percentile of 41.5 mg/p/d is
below the UL of 45 mg/p/d for adolescents 14 to 18 years of age.
Similarly, the exposure estimate to iron from all food sources and
lipstick for females 14 years of age and older of 40.2 mg/p/d at the
90th percentile is below the UL of 45 mg/p/d for adolescents and adults
(14 years of age and older). Because the EDI of iron from all current
and proposed food sources at the 90th percentile for each population
group, which was estimated using conservative assumptions, is below the
corresponding IOM UL for that population group, even without taking
into account the low bioavailability of the iron from the petitioned
uses, we conclude that there is a reasonable certainty of no harm from
the proposed use of synthetic iron oxide as a color additive in soft
and hard candy, mints, and chewing gum (Ref. 4).

C. Lead Specification

As discussed in section I, the petitioner proposed to lower the
specification limit for lead in synthetic iron oxide for human food use
in 21 CFR 73.200 from 10 mg/kg to 5 mg/kg. To support the lower lead
specification, the petitioner submitted data on lead levels from batch
analyses of synthetic iron oxide. The data demonstrates that the
proposed lead limit of 5 ppm is achievable with the use of good
manufacturing practices in the production of the color additive (Ref.
5). Because the lower specification limit is achievable, and also
because the lower specification limit is consistent with the safe use
of the color additive, we are lowering the lead specification limit for
lead in synthetic iron oxide for human food as proposed. The lower
specification applies to both the petitioned new use of synthetic iron
oxide to color candy, chewing gum, and mints, as well as to the
already-approved use of synthetic iron oxide for human food use in the
coloring of sausage casings.

V. Conclusion

Based on the data and information in the petition and other
relevant material, we conclude that the petitioned use of synthetic
iron oxide in soft and hard candy, mints, and chewing gum is safe. We
further conclude that the additive will achieve its intended technical
effect and is suitable for the petitioned use. Consequently, we are
amending the color additive regulations in 21 CFR part 73 as set forth
in this document. In addition, based upon the factors listed in 21 CFR
71.20(b), we conclude that batch certification of synthetic iron oxide
is not necessary for the protection of public health.

VI. Public Disclosure

In accordance with Sec. 71.15 (21 CFR 71.15), the petition and the
documents that we considered and relied upon in reaching our decision
to approve the petition will be made available for public disclosure
(see FOR FURTHER INFORMATION CONTACT). As provided in Sec. 71.15, we
will delete from the documents any materials that are not available for
public disclosure.

VII. Environmental Impact

We previously considered the environmental effects of this rule as
stated in the September 17, 2013, notice of filing for CAP 3C0298 (78
FR 57105). We stated that we had determined, under 21 CFR 25.32(k),
that this action is of a type that does not individually or
cumulatively have a significant effect on the human environment such
that neither an environmental assessment nor an environmental impact
statement is required. We have not received any new information or
comments that would affect our previous determination.

VIII. Paperwork Reduction Act of 1995

This final rule contains no collection of information. Therefore,
clearance by the Office of Management and Budget under the Paperwork
Reduction Act of 1995 is not required.

IX. Section 301(ll) of the FD&C Act

Our review of this petition was limited to section 721 of the FD&C
Act. This final rule is not a statement regarding compliance with other
sections of the FD&C Act. For example, the Food and Drug Administration
Amendments Act of 2007, which was signed into law on September 27,
2007, amended the FD&C Act to, among other things, add section 301(ll)
of the FD&C Act (21 U.S.C. 331(ll)). Section 301(ll) of the FD&C Act
prohibits the introduction or delivery for introduction into interstate
commerce of any food that contains a drug approved under section 505 of
the FD&C Act (21 U.S.C. 355), a biological product licensed under
section 351 of the Public Health Service Act (42 U.S.C. 262), or a drug
or biological product for which substantial clinical investigations
have been instituted and their existence has been made public, unless
one of the exemptions in section 301(ll)(1) to (ll)(4) of the FD&C Act
applies. In our review of this petition, we did not consider whether
section 301(ll) of the FD&C Act or any of its exemptions apply to food
products containing this color additive. Accordingly, this final rule
should not be construed to be a statement that a product containing
this color additive, if introduced or delivered for introduction into
interstate commerce, would not violate section 301(ll) of the FD&C Act.
Furthermore, this language is included in all color additive final
rules that pertain to food and therefore should not be construed to be
a statement of the likelihood that section 301(ll) of the FD&C Act
applies.

X. Objections

This rule is effective as shown in the DATES section, except as to
any provisions that may be stayed by the filing of proper objections.
If you will be adversely affected by one or more provisions of this
regulation, you may file with the Division of Dockets Management (see
ADDRESSES) either electronic or written objections. You must separately
number each objection, and within each numbered objection you must
specify with particularity the provision to which you object and the
grounds for your objection. Within each numbered objection, you must

[[Page 14842]]

specifically state whether you are requesting a hearing on the
particular provision that you specify in that numbered objection. If
you do not request a hearing for any particular objection, you waive
the right to a hearing on that objection. If you request a hearing,
your objection must include a detailed description and analysis of the
specific factual information you intend to present in support of the
objection in the event that a hearing is held. If you do not include
such a description and analysis for any particular objection, you waive
the right to a hearing on the objection.
It is only necessary to send one set of documents. Identify
documents with the docket number found in brackets in the heading of
this document. Any objections received in response to the regulation
may be seen in the Division of Dockets Management between 9 a.m. and 4
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov. We will publish notice of the objections that we
have received or lack thereof in the Federal Register.

XI. References

The following references have been placed on display in the
Division of Dockets Management (see ADDRESSES) and may be seen by
interested persons between 9 a.m. and 4 p.m., Monday through Friday,
and are available electronically at http://www.regulations.gov. (FDA
has verified the Web site addresses in this reference section, but FDA
is not responsible for any subsequent changes to Web sites after this
document publishes in the Federal Register.)

1. Memorandum to the File from A. Zajac, Division of Petition
Review, February 27, 2015.
2. Memorandum from D. Doell, Chemistry Review Group, Division of
Petition Review, to L. Dye, Regulatory Group II, Division of
Petition Review, June 20, 2014.
3. Institute of Medicine. Dietary Reference Intakes for Vitamin A,
Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron,
Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc.
Washington, DC: The National Academies Press, 2001.
4. Memorandum from S. Thurmond, Toxicology Team, Division of
Petition Review, to L. Dye, Regulatory Group II, Division of
Petition Review, September 9, 2014.
5. Memorandum from N. Hepp, Color Technology Team, Office of
Cosmetics and Colors, to L. Dye, Division of Petition Review,
September 23, 2013.

List of Subjects in 21 CFR Part 73

Color additives, Cosmetics, Drugs, and Medical devices.

Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, and
redelegated to the Director, Center for Food Safety and Applied
Nutrition, 21 CFR part 73 is amended as follows:

PART 73--LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION

0
1. The authority citation for 21 CFR part 73 continues to read as
follows:

Authority: 21 U.S.C. 321, 341, 342, 343, 348, 351, 352, 355,
361, 362, 371, 379e.

0
2. Section 73.200 is amended by revising paragraphs (b)(1) and (c)(1)
to read as follows:

Sec. 73.200 Synthetic iron oxide.

* * * * *
(b) * * *
(1) Synthetic iron oxide for human food use shall conform to the
following specifications:
Arsenic (as As), not more than 3 milligrams per kilogram (mg/kg) (3
parts per million (ppm)).
Lead (as Pb), not more than 5 mg/kg (5 ppm).
Mercury (as Hg), not more than 1 mg/kg (1 ppm).
* * * * *
(c) * * *
(1) Synthetic iron oxide may be safely used for human food use
subject to the following restrictions:
(i) In sausage casings intended for human consumption in an amount
not exceeding 0.10 percent by weight of the finished food.
(ii) In soft and hard candy, mints, and chewing gum at levels
consistent with good manufacturing practice, except that it may not be
used to color foods for which standards of identity have been issued
under section 401 of the Federal Food, Drug, and Cosmetic Act, unless
the use of the added color is authorized by such standards.
* * * * *

Dated: March 17, 2015.
Susan M. Bernard,
Director, Office of Regulations, Policy and Social Sciences, Center for
Food Safety and Applied Nutrition.
[FR Doc. 2015-06418 Filed 3-19-15; 8:45 am]
BILLING CODE 4164-01-P

14840 Federal Register / Vol. 80, No. 54 / Friday, March 20, 2015 / Rules and Regulations

a blend of various iron oxides. For the and chewing gum based on the that all of the iron present is
subject petition, synthetic iron oxides maximum anticipated use levels; (2) the bioavailable. We have no further
are intended to be used in soft and hard current use of synthetic iron oxide to questions regarding Wrigley’s exposure
candy, mints, and chewing gum in color sausage casings; (3) background estimates for iron in food and cosmetics
amounts consistent with GMP. The iron from conventional food based on and conclude that the petitioner’s
maximum GMP use level for iron oxides the iron content declared on food labels; exposure estimates are sufficiently
depends on the color of the iron oxide (4) iron from dietary supplements; and conservative to account for the use of
and the application. We have (5) oral exposure to iron oxides from iron oxides in ingested drugs (Ref. 2).
determined that the amount of the color their use as color additives in lipstick. We also conclude that exposure from
additive used in these foods is self- These exposure estimates assumed that indirect uses of iron oxides, such as for
limiting (Ref. 1). Therefore, there is no all of the iron that is present is absorbed colorants for food-contact polymers
need for a specific upper limit on the in the gastrointestinal tract. Wrigley also authorized in 21 CFR 178.3297, would
percent by weight of iron oxide in hard provided exposure estimates to iron that not significantly contribute to the
and soft candies, mints, and chewing took into account the bioavailability of overall exposure to iron oxides.
gum in the regulation for these foods. iron from all current dietary sources, To address the bioavailability of iron,
proposed uses, and lipstick. Wrigley Wrigley provided information showing
III. Evaluation of Safety approximately 18 percent of iron from
compared these intake estimates to the
Under section 721(b)(4) of the Federal Tolerable Upper Intake Level (UL) for conventional foods and dietary
Food, Drug, and Cosmetic Act (the iron established by the Institute of supplements is bioavailable, and that
FD&C Act) (21 U.S.C. 379e(b)(4)), a color Medicine (IOM) of the National about 1 percent of iron from synthetic
additive cannot be listed for a particular Academies. Based on this and other iron oxide is bioavailable. Based on this
use unless the data and information information, Wrigley concluded that the information, Wrigley provided exposure
available to FDA establishes that the proposed use of synthetic iron oxide to estimates that take into account the
color additive is safe for that use. FDA’s color soft and hard candy, mints, and bioavailability of iron. Wrigley
color additive regulations in 21 CFR chewing gum is safe. estimated the exposure to bioavailable
70.3(i) define ‘‘safe’’ to mean that there iron from the proposed uses at the 90th
is convincing evidence that establishes A. Estimated Daily Intake of Iron percentile to be 0.16 mg/p/d, 0.12 mg/
with reasonable certainty that no harm Using food consumption data from p/d, 0.16 mg/p/d, and 0.16 mg/p/d for
will result from the intended use of the the 2003–2008 National Health and the U.S. population (2 years of age and
color additive. To establish with Nutrition Examination Survey older), children 2 to 5 years of age,
reasonable certainty that a color (NHANES), Wrigley’s estimated children 2 to 13 years of age, and
additive intended for use in food is not exposure to iron from the proposed uses adolescents and adults 14 years of age
harmful under its intended conditions in soft and hard candy, mints and and older, respectively. Wrigley
of use, we consider the estimated chewing gum for the U.S. population (2 estimated the cumulative exposure to
human dietary exposure to the additive, years of age and older) to be 16.3 mg/ bioavailable iron from all food sources
the additive’s toxicological data, and p/day (d) for the 90th percentile (current and proposed) at the 90th
other relevant information (such as consumer. Wrigley also provided percentile to be 6.02 mg/p/d, 4.68 mg/
published literature) available to us. We dietary exposure estimates to iron for p/d, 4.99 mg/p/d, and 6.21 mg/p/d for
compare an individual’s estimated daily children 2 to 5 years of age, children 2 the U.S. population (2 years of age and
intake (EDI) of the additive from all to 13 years of age, and adolescents and older), children 2 to 5 years of age,
sources to an acceptable daily intake adults 14 years of age and older. For children 2 to 13 years of age, and
(ADI) established by toxicological data. these population groups, Wrigley adolescents and adults 14 years of age
The EDI is determined by projections estimated the exposure to iron from the and older, respectively. For females 10
based on the amount of the additive proposed uses at the 90th percentile to to 13 years old, and 14 years of age and
proposed for use in particular foods and be 12.2 mg/p/d, 15.6 mg/p/d, and 16.4 older, Wrigley estimated exposure to
on data regarding the amount consumed mg/p/d, respectively. Wrigley also bioavailable iron from all food sources
from all sources of the additive. We estimated the cumulative exposure to (current and proposed) and lipstick to
typically use the EDI for the 90th iron from all food sources (current and be 5.07 mg/p/d and 6.12 mg/p/d,
percentile consumer of a color additive proposed) for the U.S. population (2 respectively (Ref. 2).
as a measure of high chronic dietary years of age and older) to be 40.6 mg/
exposure. p/d for the 90th percentile consumer. B. Acceptable Intake Level for Iron
Wrigley also provided dietary exposure In 2000, the Standing Committee on
IV. Safety of Petitioned Use of the estimates to iron for children 2 to 5 the Scientific Evaluation of Dietary
Additive years of age, children 2 to 13 years of Reference Intakes of the Food and
To support the safety of the proposed age, and adolescents and adults 14 years Nutrition Board at the IOM conducted
uses of synthetic iron oxide, Wrigley of age and older. For these population an extensive review of relevant
provided information about iron intake groups, Wrigley estimated the exposure published scientific literature to
expected to result from the proposed to iron at the 90th percentile to be 31.2 determine dietary reference intakes and
new uses of synthetic iron oxide, as well mg/p/d, 34.6 mg/p/d, and 41.5 mg/p/d, ULs for iron. The IOM published a
as intake from other sources of iron. respectively. In addition, Wrigley detailed report that included a UL for
There are many dietary sources of iron, estimated exposure to iron from all food iron of 40 mg/d for children (2 to 5 years
including from food ingredients, dietary sources (current and proposed) and of age and 2 to 13 years of age), and a
mstockstill on DSK4VPTVN1PROD with RULES

supplements, and from food that lipstick for females 10 to 13 years old, UL of 45 mg/d for adolescents and
contains naturally occurring iron. and 14 years of age and older. The adults (14 years of age and older) (Ref.
Specifically, Wrigley submitted detailed exposure at the 90th percentile for these 3).
exposure estimates of iron that took into two population groups was 33.8 mg/p/ The IOM considers the UL as the
account the following: (1) The proposed d and 40.2 mg/p/d, respectively. highest daily intake level of a nutrient
uses of synthetic iron oxide as a color Wrigley noted that these exposure that poses no risk of adverse effects
additive in soft and hard candy, mints, estimates are conservative and assume when the nutrient is consumed over

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Federal Register / Vol. 80, No. 54 / Friday, March 20, 2015 / Rules and Regulations 14841

long periods of time. The UL is iron oxide for human food use in 21 would affect our previous
determined using a risk assessment CFR 73.200 from 10 mg/kg to 5 mg/kg. determination.
model developed specifically for To support the lower lead specification,
VIII. Paperwork Reduction Act of 1995
nutrients and, generally speaking, may the petitioner submitted data on lead
consider intake from such sources as levels from batch analyses of synthetic This final rule contains no collection
food, water, nutrient supplements, and iron oxide. The data demonstrates that of information. Therefore, clearance by
pharmacological agents. The dose- the proposed lead limit of 5 ppm is the Office of Management and Budget
response assessment, which concludes achievable with the use of good under the Paperwork Reduction Act of
with an estimate of the UL, is built upon manufacturing practices in the 1995 is not required.
three toxicological concepts commonly production of the color additive (Ref. 5). IX. Section 301(ll) of the FD&C Act
used in assessing the risk of exposures Because the lower specification limit is
to chemical substances: No-observed- achievable, and also because the lower Our review of this petition was
adverse-effect level, lowest-observed- specification limit is consistent with the limited to section 721 of the FD&C Act.
effect level, and an uncertainty factor. safe use of the color additive, we are This final rule is not a statement
We considered the ULs established by lowering the lead specification limit for regarding compliance with other
the IOM relative to the intake estimates lead in synthetic iron oxide for human sections of the FD&C Act. For example,
as the primary basis for assessing the food as proposed. The lower the Food and Drug Administration
safety of iron from the proposed uses of specification applies to both the Amendments Act of 2007, which was
synthetic iron oxide. We also reviewed petitioned new use of synthetic iron signed into law on September 27, 2007,
scientific articles on the safety of iron oxide to color candy, chewing gum, and amended the FD&C Act to, among other
submitted by Wrigley, as well as other mints, as well as to the already- things, add section 301(ll) of the FD&C
relevant published studies available to approved use of synthetic iron oxide for Act (21 U.S.C. 331(ll)). Section 301(ll) of
FDA. human food use in the coloring of the FD&C Act prohibits the introduction
The exposure estimates to iron from sausage casings. or delivery for introduction into
all food sources, including the proposed interstate commerce of any food that
use of synthetic iron oxide in soft and V. Conclusion contains a drug approved under section
hard candy, mints, and chewing gum, at Based on the data and information in 505 of the FD&C Act (21 U.S.C. 355), a
the 90th percentile for children 2 to 5 the petition and other relevant material, biological product licensed under
years of age and for children 2 to 13 we conclude that the petitioned use of section 351 of the Public Health Service
years of age, without taking into account synthetic iron oxide in soft and hard Act (42 U.S.C. 262), or a drug or
the bioavailability of the iron, is 31.2 candy, mints, and chewing gum is safe. biological product for which substantial
mg/p/d and 34.6 mg/p/d, respectively. We further conclude that the additive clinical investigations have been
Both of these exposure estimates are will achieve its intended technical effect instituted and their existence has been
below the UL for these age groups. The and is suitable for the petitioned use. made public, unless one of the
exposure estimate to iron from all food Consequently, we are amending the exemptions in section 301(ll)(1) to (ll)(4)
sources (current and proposed) and color additive regulations in 21 CFR of the FD&C Act applies. In our review
lipstick for females 10 to 13 years old part 73 as set forth in this document. In of this petition, we did not consider
at the 90th percentile of 33.8 mg/p/d is addition, based upon the factors listed whether section 301(ll) of the FD&C Act
also below the UL established for this in 21 CFR 71.20(b), we conclude that or any of its exemptions apply to food
group. For adolescents and adults 14 batch certification of synthetic iron products containing this color additive.
years of age and older, the exposure oxide is not necessary for the protection Accordingly, this final rule should not
estimate for iron at the 90th percentile of public health. be construed to be a statement that a
of 41.5 mg/p/d is below the UL of 45 product containing this color additive, if
mg/p/d for adolescents 14 to 18 years of VI. Public Disclosure introduced or delivered for introduction
age. Similarly, the exposure estimate to In accordance with § 71.15 (21 CFR into interstate commerce, would not
iron from all food sources and lipstick 71.15), the petition and the documents violate section 301(ll) of the FD&C Act.
for females 14 years of age and older of that we considered and relied upon in Furthermore, this language is included
40.2 mg/p/d at the 90th percentile is reaching our decision to approve the in all color additive final rules that
below the UL of 45 mg/p/d for petition will be made available for pertain to food and therefore should not
adolescents and adults (14 years of age public disclosure (see FOR FURTHER be construed to be a statement of the
and older). Because the EDI of iron from INFORMATION CONTACT). As provided in likelihood that section 301(ll) of the
all current and proposed food sources at § 71.15, we will delete from the FD&C Act applies.
the 90th percentile for each population documents any materials that are not
X. Objections
group, which was estimated using available for public disclosure.
conservative assumptions, is below the This rule is effective as shown in the
VII. Environmental Impact DATES section, except as to any
corresponding IOM UL for that
population group, even without taking We previously considered the provisions that may be stayed by the
into account the low bioavailability of environmental effects of this rule as filing of proper objections. If you will be
the iron from the petitioned uses, we stated in the September 17, 2013, notice adversely affected by one or more
conclude that there is a reasonable of filing for CAP 3C0298 (78 FR 57105). provisions of this regulation, you may
certainty of no harm from the proposed We stated that we had determined, file with the Division of Dockets
use of synthetic iron oxide as a color under 21 CFR 25.32(k), that this action Management (see ADDRESSES) either
mstockstill on DSK4VPTVN1PROD with RULES

additive in soft and hard candy, mints, is of a type that does not individually electronic or written objections. You
and chewing gum (Ref. 4). or cumulatively have a significant effect must separately number each objection,
on the human environment such that and within each numbered objection
C. Lead Specification neither an environmental assessment you must specify with particularity the
As discussed in section I, the nor an environmental impact statement provision to which you object and the
petitioner proposed to lower the is required. We have not received any grounds for your objection. Within each
specification limit for lead in synthetic new information or comments that numbered objection, you must

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Document Created: 2015-12-18 11:34:44
Document Modified: 2015-12-18 11:34:44

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Rules and Regulations
Action		Final rule.
Dates		This rule is effective April 21, 2015. See section X for further information on the filing of objections. Submit either electronic or written objections and requests for a hearing by April 20, 2015.
Contact		Laura A. Dye, Center for Food Safety and Applied Nutrition (HFS-265), Food and Drug Administration, 5100 Paint Branch Pkwy., College Park, MD 20740-3835, 240-402-1275.
FR Citation		80 FR 14839
CFR Associated		Color Additives; Cosmetics; Drugs and Medical Devices

80 FR 14839 - Listing of Color Additives Exempt From Certification; Synthetic Iron Oxide

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 80, Issue 54 (March 20, 2015)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration