[Federal Register Volume 80, Number 54 (Friday, March 20, 2015)]
[Rules and Regulations]
[Pages 14839-14842]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[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