81 FR 46578 - Food Additives Permitted for Direct Addition to Food for Human Consumption; Vitamin D2

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 81, Issue 137 (July 18, 2016)

Page Range		46578-46582
FR Document		2016-16738

The Food and Drug Administration (FDA or we) is amending the food additive regulations to expand the safe uses of vitamin D<INF>2</INF> as a nutrient supplement in edible plant-based beverages intended for use as milk alternatives and in edible plant-based yogurt alternatives and vitamin D<INF>3</INF> as a nutrient supplement in milk at levels higher than those currently permitted. We are taking this action in response to a food additive petition filed by Dean Foods Company and WhiteWave Foods Company.

Federal Register, Volume 81 Issue 137 (Monday, July 18, 2016)

[Federal Register Volume 81, Number 137 (Monday, July 18, 2016)]
[Rules and Regulations]
[Pages 46578-46582]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2016-16738]

[[Page 46578]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 172

[Docket No. FDA-2013-N-0888]

Food Additives Permitted for Direct Addition to Food for Human
Consumption; Vitamin D2 and Vitamin D3

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
food additive regulations to expand the safe uses of vitamin
D2 as a nutrient supplement in edible plant-based beverages
intended for use as milk alternatives and in edible plant-based yogurt
alternatives and vitamin D3 as a nutrient supplement in milk
at levels higher than those currently permitted. We are taking this
action in response to a food additive petition filed by Dean Foods
Company and WhiteWave Foods Company.

DATES: This rule is effective July 18, 2016. See section VIII for
further information on the filing of objections. Submit either
electronic or written objections and requests for a hearing by August
17, 2016. The Director of the Federal Register approves the
incorporation by reference of certain publications listed in the rule
as of July 18, 2016.

ADDRESSES: You may submit objections and requests for a hearing as
follows:

Electronic Submissions

Submit electronic objections in the following way:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments. Objections submitted
electronically, including attachments, to http://www.regulations.gov
will be posted to the docket unchanged. Because your objection will be
made public, you are solely responsible for ensuring that your
objection does not include any confidential information that you or a
third party may not wish to be posted, such as medical information,
your or anyone else's Social Security number, or confidential business
information, such as a manufacturing process. Please note that if you
include your name, contact information, or other information that
identifies you in the body of your objection, that information will be
posted on http://www.regulations.gov.
If you want to submit an objection with confidential
information that you do not wish to be made available to the public,
submit the objection as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

Submit written/paper submissions as follows:
Mail/Hand delivery/Courier (for written/paper
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper objections submitted to the Division of
Dockets Management, FDA will post your objection, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2013-N-0888 for ``Food Additives Permitted for Direct Addition to
Food for Human Consumption; Vitamin D2 and Vitamin
D3 Final Rule.'' Received objections will be placed in the
docket and, except for those submitted as ``Confidential Submissions,''
publicly viewable at http://www.regulations.gov or at the Division of
Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.
Confidential Submissions--To submit an objection with
confidential information that you do not wish to be made publicly
available, submit your objections only as a written/paper submission.
You should submit two copies total. One copy will include the
information you claim to be confidential with a heading or cover note
that states ``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The
Agency will review this copy, including the claimed confidential
information, in its consideration of comments. The second copy, which
will have the claimed confidential information redacted/blacked out,
will be available for public viewing and posted on http://www.regulations.gov. Submit both copies to the Division of Dockets
Management. If you do not wish your name and contact information to be
made publicly available, you can provide this information on the cover
sheet and not in the body of your comments and you must identify this
information as ``confidential.'' Any information marked as
``confidential'' will not be disclosed except in accordance with 21 CFR
10.20 and other applicable disclosure law. For more information about
FDA's posting of comments to public dockets, see 80 FR 56469, September
18, 2015, or access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments 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: Judith Kidwell, Center for Food Safety
and Applied Nutrition (CFSAN) (HFS-265), Food and Drug Administration,
5100 Paint Branch Pkwy., College Park, MD 20740-3835, 240-402-1071.

SUPPLEMENTARY INFORMATION:

I. Background

In a document published in the Federal Register of August 16, 2013
(78 FR 49990), FDA announced that Dean Foods Company (Dean Foods) and
WhiteWave Foods Company (WhiteWave), c/o Hogan Lovells US LLP, Columbia
Square, 555 13th Street NW., Washington, DC 20004, had jointly filed a
food additive petition (FAP 3A4801). The petition proposed to amend 21
CFR 172.379 to provide for the safe use of vitamin D2 as a
nutrient supplement in edible plant-based food products intended for
use as alternatives to milk and milk products and to amend 21 CFR
172.380 to provide for the safe use of vitamin D3 as a
nutrient supplement in milk at levels higher than those currently
permitted. After the notice of filing published, the petitioners
amended the petition to limit the proposed use of vitamin D2
to only edible plant-based beverages intended as alternatives to milk
(e.g., soy-, rice-, almond-, coconut-based beverages) and edible plant-
based yogurt alternatives. This final rule is a complete response to
the petition.
Dean Foods/WhiteWave have requested that we amend Sec. 172.379 to
authorize the use of vitamin D2 as a nutrient supplement at
levels not to exceed 84 International Units (IU) per 100 grams (g) in
edible plant-based beverages intended for use as milk alternatives and
not to exceed 89 IU per 100 g in edible plant-based yogurt
alternatives. Dean Foods/WhiteWave requested that the proposed use of
84 IU vitamin D2 per 100 g in edible plant-based beverages
replace the current allowable maximum use of 50 IU per 100 g in soy
beverages authorized under

[[Page 46579]]

Sec. 172.379(c). Specifically, Dean Foods/WhiteWave requested that we
amend Sec. 172.379(c) to eliminate the ``soy beverages'' category, and
instead create a new category of food that may be supplemented with
vitamin D2. This category, ``edible plant-based beverages
intended for use as milk alternatives'', would include soy beverages
intended as milk alternatives, and would have a maximum allowable use
of 84 IU vitamin D2 per 100 g. This category would also
include other edible plant-based beverages made from rice, almond, and
coconut, among other foods, that are intended as milk alternatives.
Dean Foods/WhiteWave also requested that we amend Sec. 172.380 to
allow for the addition of vitamin D3 as a nutrient
supplement in milk at levels not to exceed 84 IU per 100 g milk. For
milk with more than the amount of vitamin D provided for in the milk
standard of identity in 21 CFR 131.110(b)(2), the milk would be
required to be named by use of a nutrient content claim and a
standardized term in accordance with 21 CFR 130.10.
Vitamin D comprises a group of fat-soluble seco-sterols and comes
in many forms. The two major physiologically relevant forms are vitamin
D2 and vitamin D3. Vitamin D without a subscript
represents either vitamin D2 or vitamin D3 or
both. Vitamin D is affirmed as generally recognized as safe (GRAS) for
use in food as a nutrient supplement in accordance with 21 CFR
184.1950(c)(1) and 21 CFR 184.1(b)(2), with the following specific
limitations:

------------------------------------------------------------------------
Maximum levels in food (as
Category of food served)
------------------------------------------------------------------------
Breakfast cereals......................... 350 IU/100 grams (g).
Grain products and pasta.................. 90 IU/100 g.
Milk...................................... 42 IU/100 g.
Milk products............................. 89 IU/100 g.
------------------------------------------------------------------------

Additionally, under Sec. 184.1950(c)(2) and (3), vitamin D is
affirmed as GRAS for use in infant formulas and margarine,
respectively. Under Sec. 172.380, vitamin D3 is approved
for use as a food additive as a nutrient supplement in calcium-
fortified fruit juices and fruit juice drinks, meal replacement and
other type bars, soy protein-based meal replacement beverages
represented for special dietary use in reducing or maintaining body
weight, certain cheese and cheese products, meal replacement beverages
that are not intended for special dietary use in reducing or
maintaining body weight, and foods represented for use as a sole source
of nutrition for enteral feeding.
Under Sec. 172.379, vitamin D2 is approved for use as a
food additive as a nutrient supplement in soy beverages, soy beverage
products, soy-based butter substitute spreads, and soy-based cheese
substitutes, and soy-based cheese substitute products.
Under Sec. 172.381, vitamin D2 bakers yeast is approved
for use as a food additive as a source of vitamin D2 and as
a leavening agent in yeast-leavened baked goods and baking mixes and
yeast-leavened baked snack foods.
Vitamin D is essential for human health. The major function of
vitamin D is the maintenance of blood serum concentrations of calcium
and phosphorus by enhancing the absorption of these minerals in the
small intestine. Vitamin D deficiency can lead to abnormalities in
calcium and bone metabolism, such as rickets in children or
osteomalacia in adults. Excessive intake of vitamin D elevates blood
plasma calcium levels (hypercalcemia) by increased intestinal
absorption and/or mobilization from the bone.
To ensure that vitamin D is not added to the U.S. food supply at
levels that could raise safety concerns, FDA affirmed vitamin D as GRAS
with specific limitations as listed in Sec. 184.1950. Under Sec.
184.1(b)(2), an ingredient affirmed as GRAS with specific limitations
may be used in food only within such limitations, including the
category of food, functional use of the ingredient, and level of use.
Any addition of vitamin D to food beyond those limitations set out in
Sec. 184.1950 requires either a food additive regulation or an
amendment of Sec. 184.1950.
To support their petition, Dean Foods/WhiteWave submitted dietary
exposure estimates of vitamin D from the proposed uses of vitamin
D2 and vitamin D3, as well as all dietary sources
from naturally occurring sources of vitamin D and uses in accordance
with our approved food additive regulations (Sec. Sec. 172.379,
172.380, and 172.381) and our GRAS affirmation regulation (Sec.
184.1950). They also included dietary supplements in their estimates
and compared these intake estimates to the Tolerable Upper Intake Level
(UL) for vitamin D established by the Institute of Medicine (IOM) of
the National Academies. Dean Foods/WhiteWave also submitted a number of
publications pertaining to human clinical studies on vitamin D. Based
on this information, Dean Foods/WhiteWave concluded that the proposed
uses of vitamin D2 in edible plant-based beverages intended
as alternatives to milk, edible plant-based yogurt alternatives, and
vitamin D3 in milk are safe.

II. Evaluation of Safety

To establish with reasonable certainty that a food additive is not
harmful under its intended conditions of use, we consider the projected
human dietary exposure to the additive, the additive's toxicological
data, and other relevant information (such as published literature)
available to us. We compare the estimated daily intake (EDI) of the
additive from all food sources to an acceptable daily intake level
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 food sources
of the additive. We commonly use the EDI for the 90th percentile
consumer of a food additive as a measure of high chronic dietary
intake.

A. Acceptable Daily Intake Level for Vitamin D

In 2011, 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 on vitamin D to update current dietary reference intakes and
ULs for vitamin D. Based on this information, the IOM revised the ULs
for vitamin D and developed a report on their findings (Ref. 1). In
their 2011 assessment of vitamin D, the IOM established a UL of 1,000
IU per day (IU/p/d) for infants 0 months to 6 months of age and a UL of
1,500 IU/p/d for infants 6 months to 12 months of age. For children 1
year to 3 years of age, the IOM established a UL of 2,500 IU/p/d; for
children 4 years to 8 years of age, the IOM established a UL of 3,000
IU/p/d. For children 9 years to 18 years of age and adults, the IOM
established a UL of 4,000 IU/p/d.
The IOM considers the UL as the highest average daily intake level
of a nutrient that poses no risk of adverse effects when the nutrient
is consumed over long periods of time. The UL is determined using a
risk assessment model developed specifically for nutrients. 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 application of an uncertainty
factor. We considered the ULs established by the IOM relative to

[[Page 46580]]

the intake estimates as the primary basis for assessing the safety of
the petitioned uses of vitamin D2 and vitamin D3.
We also reviewed scientific articles on the safety of vitamin D
submitted in the petition, as well as other relevant published studies
available to FDA.

B. Estimated Daily Intake for Vitamin D

For the proposed uses of vitamin D2 and vitamin
D3, Dean Foods/WhiteWave provided dietary intake estimates
of vitamin D for 11 population groups, assuming maximum levels of
vitamin D in all foods that could be fortified (except for one scenario
where typical fortification levels in infant formula were used), as
well as in the petitioned foods. They also included exposure from
dietary supplements as reported in the 2003-2008 National Health and
Nutrition Survey (NHANES) 30-day dietary supplement use data (http://wwwn.cdc.gov/nchs/nhanes/search/datapage.aspx?Component=dietary) and
from naturally occurring food sources.
The exposure estimates performed by Dean Foods/WhiteWave are
appropriate. However, there are some exposure parameters that have
changed since the estimates were completed in 2013. In particular, Dean
Foods/WhiteWave provided estimates that included vitamin D exposure
from fortification of edible plant-based dairy analogs other than
edible plant-based yogurt alternatives, which they are no longer
seeking to fortify. Dean Food/WhiteWave also included fortification of
meal replacement bars at a level of 500 IU/40 g in anticipation of the
approval of FAP 2A4788 (Abbott Laboratories); however, this use was
subsequently withdrawn from the petition before the final rule issued
(see 79 FR 46993, August 12, 2014). In addition, more recent 24-hour
recall dietary supplement data from the 2009-2012 NHANES (http://wwwn.cdc.gov/nchs/nhanes/search/datapage.aspx?Component=dietary) have
become available that may better represent current vitamin D exposure
from dietary supplements than the 30-day dietary supplement use data
from the 2003-2008 NHANES used by Dean Foods/WhiteWave. Moreover, a
recent published study suggests that it may be appropriate to include
dietary sources of the vitamin D metabolite, 25-hydroxyvitamin D
(25(OH)D), in vitamin D exposure estimates to take into account
discrepancies seen between dietary intake and blood serum levels of
vitamin D (Ref. 2). The foods that were identified in the study as
sources of 25(OH)D were beef, pork, chicken, turkey, and eggs. The
study also indicated that 25(OH)D may have a potency five times that of
vitamin D. For these reasons, we have used the 2009-2012 NHANES data to
estimate dietary exposure to vitamin D from: (1) The petitioned uses in
milk, edible plant-based beverages intended as milk alternatives, and
edible plant-based yogurt alternatives; and (2) cumulative exposure
from all current sources of vitamin D (i.e., naturally occurring
sources, approved fortified sources, and dietary supplements), the
petitioned uses of vitamin D in milk, edible plant-based beverages
intended as milk alternatives, and edible plant-based yogurt, and
exposure from sources of 25(OH)D, which have been adjusted to account
for the difference in potency between 25(OH)D and vitamin D.
For the overall U.S. population 1 year of age and older, the
cumulative exposure at the 90th percentile from all food sources of
vitamin D, including the proposed uses, dietary supplements, and
25(OH)D, was estimated to be 2,000 IU/p/d. The cumulative exposure for
infants 0 to 6 months of age and infants 6 to 12 months of age from all
food sources of vitamin D, including the proposed uses, dietary
supplements, and 25(OH)D, was estimated to be 948 IU/p/d and 988 IU/p/
d, respectively, for the 90th percentile consumer (Ref. 3).

C. Safety of the Petitioned Uses of Vitamin D2

We reviewed and evaluated the information submitted by Dean Foods/
WhiteWave regarding the safety of the dietary intake of vitamin D from
the proposed uses in milk, edible plant-based beverages intended as
milk alternatives, and edible plant-based yogurt alternatives. Dean
Food/WhiteWave submitted reports of scientific studies published
subsequent to the 1997 IOM report and issuance of the final rule (79 FR
46993) authorizing the use of vitamin D3 in meal replacement
beverages that are not intended for special dietary use in reducing or
maintaining body weight and in foods represented for use as a sole
source of nutrition for enteral feeding. Dean Food/WhiteWave concluded
that these publications support a conclusion that the proposed use of
vitamin D is safe.
We reviewed the published reports of scientific studies on vitamin
D submitted by Dean Food/WhiteWave, as well as other relevant published
studies available to us since our previous evaluations of six food
additive petitions for fortifying a variety of foods with vitamin D (77
FR 52228, August 29, 2012; 74 FR 11019, March 16, 2009; 70 FR 69435,
November 16, 2005; 70 FR 37255, June 29, 2005; 70 FR 36021, June 22,
2005; 68 FR 9000, February 27, 2003). These studies did not raise any
new safety concerns regarding the current or proposed uses of vitamin
D. The most recent food additive petition resulted in our amendment of
the food additive regulations in Sec. 172.380 to allow for the safe
use of vitamin D3 in meal replacement beverages that are not
intended for special dietary use in reducing or maintaining body weight
and in foods represented for use as a sole source of nutrition for
enteral feeding (79 FR 46993). The six earlier food additive petitions
also resulted in amendments of the food additive regulations to allow
for the safe use of vitamin D as a nutrient supplement in certain
foods.
We considered the ULs established by the IOM relative to the intake
estimates as the primary basis for assessing the safety of the
petitioned uses of vitamin D. Depending on the age group, the IOM UL
for vitamin D for the U.S. population 1 year of age and older ranges
from 2,500 IU/p/d to 4,000 IU/p/d. The estimated dietary exposure to
vitamin D from all food sources, including the proposed uses, at the
90th percentile for the U.S. population (1 years of age and older) is
estimated to be 2,000 IU/p/d, which is below the lowest IOM UL of 2,500
IU/p/d in the range of ULs for the overall U.S. population (1 year of
age and older). Estimated exposure to vitamin D from all food sources,
including the proposed uses, for infants 0 months to 6 months of age at
the 90th percentile is 948 IU/p/d; for infants 6 months to 12 months of
age, estimated exposure to vitamin D is 988 IU/p/d. Both of these
estimates are below the IOM UL of 1,000 IU/p/d for infants 0 months to
6 months of age and 1,500 IU/p/d for infants 6 months to 12 months of
age. Because the 90th percentile EDI of vitamin D from all current and
proposed food sources for each population group is less than the
corresponding IOM UL for that population group, we conclude that
dietary intake of vitamin D2 from the proposed use as a
nutrient supplement in edible plant-based beverages intended as milk
alternatives and edible plant-based yogurt alternatives and the
proposed increased maximum permitted level of vitamin D3 in
milk are safe (Ref. 4).

III. Incorporation by Reference

FDA is incorporating by reference two monographs from the Food
Chemicals Codex 9th Edition (FCC 9), which was approved by the Office
of the Federal Register. You may purchase a copy of the material from
the United States Pharmacopeial Convention, 12601

[[Page 46581]]

Twinbrook Pkwy., Rockville, MD 20852, 1-800-227-8772, http://www.usp.org/.
The current regulation for the use of vitamin D3 in food
(Sec. 172.380) indicates that the additive must meet the
specifications in the FCC 8. The more current FCC is the 9th Edition.
The current regulation for vitamin D2 (Sec. 172.379)
indicates the additive must meet the specifications in the 7th edition
of the FCC (FCC 7). Because the specifications for vitamin
D2 and vitamin D3 in FCC 9 are identical to those
in FCC 7 and FCC 8, respectively, Dean Foods/WhiteWave requested that
the respective regulations be updated to reference the specifications
in FCC 9. Therefore, we are amending Sec. Sec. 172.379 and 172.380 by
adopting the specifications for vitamin D2 and vitamin
D3 in FCC 9 in place of FCC 7 and FCC 8, respectively.

IV. Conclusion

Based on all data relevant to vitamin D that we reviewed, we
conclude that the petitioned uses of vitamin D in milk and edible
plant-based beverages intended as milk alternatives and edible plant-
based yogurt alternatives within the limits proposed by Dean Food/
WhiteWave are safe. Consequently, we are amending the food additive
regulations as set forth in this document.

V. Public Disclosure

In accordance with Sec. 171.1(h) (21 CFR 171.1(h)), 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.
171.1(h), we will delete from the documents any materials that are not
available for public disclosure.

VI. Analysis of Environmental Impact

We previously considered the environmental effects of this rule, as
stated in the August 16, 2013, Federal Register document of petition
for FAP 3A4801. 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.

VII. 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.

VIII. 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(s) to which you object, and
the grounds for your objection. Within each numbered objection, you
must 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.
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.

IX. Section 301(ll) of the Federal Food, Drug, and Cosmetic Act

Our review of this petition was limited to section 409 of the
Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 348).
This final rule is not a statement regarding compliance with other
sections of the FD&C Act. For example, section 301(ll) of the FD&C Act
(21 U.S.C. 331(ll)) 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 (4) of the FD&C Act applies. In our review of this
petition, FDA did not consider whether section 301(ll) of the FD&C Act
or any of its exemptions apply to food containing this additive.
Accordingly, this final rule should not be construed to be a statement
that a food containing this 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
food additive final rules and therefore should not be construed to be a
statement of the likelihood that section 301(ll) of the FD&C Act
applies.

X. References

References marked with an asterisk (*) are on display at the
Division of Dockets Management (see ADDRESSES), under Docket No. FDA-
2013-N-0888, and are available for viewing by interested persons
between 9 a.m. and 4 p.m., Monday through Friday; they are also
available electronically at http://www.regulations.gov. References
without asterisks are not on display; they are available as published
articles and books.

1. Committee to Review Dietary Reference Intakes for Vitamin D and
Calcium, Food and Nutrition Board, Institute of Medicine, ``Dietary
Reference Intakes for Calcium and Vitamin D,'' National Academies
Press, Washington, DC, 2011.
2. Taylor, C., K. Patterson, J. Roseland, et al., ``Including Food
25-Hydroxyvitamin D in Intake Estimates May Reduce the Discrepancy
Between Dietary and Serum Measures of Vitamin D Status,'' Journal of
Nutrition, 144:654-659, 2014.
*3. FDA Memorandum from D. Folmer, CFSAN Chemistry Review Group,
Division of Petition Review, to J. Kidwell, Regulatory Group I,
Division of Petition Review, January 27, 2016.
*4. FDA Memorandum from T. Tyler, CFSAN Toxicology Team, Division of
Petition Review, to J. Kidwell, Division of Petition Review,
February 10, 2016.

List of Subjects in 21 CFR Part 172

Food additives, Incorporation by reference, Reporting and
recordkeeping requirements.

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 172 is amended as follows:

PART 172--FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR
HUMAN CONSUMPTION

0
1. The authority citation for part 172 continues to read as follows:

Authority: 21 U.S.C. 321, 341, 342, 348, 371, 379e.

0
2. Amend Sec. 172.379 by revising the first sentence in paragraph (b)
and revising the table in paragraph (c) by removing the entry for ``Soy
beverages'' and adding entries for ``Edible plant-

[[Page 46582]]

based beverages intended as milk alternatives'' and ``Edible plant-
based yogurt alternatives'' in alphabetical order to read as follows:

Sec. 172.379 Vitamin D2.

* * * * *
(b) Vitamin D2 meets the specifications of the 2015 Food
Chemical Codex, 9th edition (through Third Supplement), effective
December 1, 2015, pp. 1260-1261, which is incorporated by reference. *
* *
(c) * * *

------------------------------------------------------------------------
Maximum levels in food (as
Category of food served)
------------------------------------------------------------------------
Edible plant-based beverages intended as 84 IU/100 g.
milk alternatives.
Edible plant-based yogurt alternatives.... 89 IU/100 g.

* * * * *
------------------------------------------------------------------------

0
3. Amend Sec. 172.380 by revising the first sentence in paragraph (b)
and by adding paragraph (c)(8) to read as follows:

Sec. 172.380 Vitamin D3.

* * * * *
(b) Vitamin D3 meets the specifications of the 2015 Food
Chemical Codex, 9th edition (through Third Supplement), effective
December 1, 2015, pp. 1261-1262, which is incorporated by reference. *
* *
(c) * * *
(8) At levels not to exceed 84 IU per 100 g (800 IU/quart) in milk
that contains more than 42 IU vitamin D per 100 g (400 IU/quart) and
that meets the requirements for foods named by use of a nutrient
content claim and a standardized term in accordance with Sec. 130.10
of this chapter.

Dated: July 11, 2016.
Susan Bernard,
Director, Office of Regulations, Policy and Social Sciences, Center for
Food Safety and Applied Nutrition.
[FR Doc. 2016-16738 Filed 7-15-16; 8:45 am]
BILLING CODE 4164-01-P

Federal Register / Vol. 81, No. 137 / Monday, July 18, 2016 / Rules and Regulations 46579

§ 172.379(c). Specifically, Dean Foods/ a sole source of nutrition for enteral as alternatives to milk, edible plant-
WhiteWave requested that we amend feeding. based yogurt alternatives, and vitamin
§ 172.379(c) to eliminate the ‘‘soy Under § 172.379, vitamin D2 is D3 in milk are safe.
beverages’’ category, and instead create approved for use as a food additive as
a nutrient supplement in soy beverages, II. Evaluation of Safety
a new category of food that may be
supplemented with vitamin D2. This soy beverage products, soy-based butter To establish with reasonable certainty
category, ‘‘edible plant-based beverages substitute spreads, and soy-based cheese that a food additive is not harmful
intended for use as milk alternatives’’, substitutes, and soy-based cheese under its intended conditions of use, we
would include soy beverages intended substitute products. consider the projected human dietary
as milk alternatives, and would have a Under § 172.381, vitamin D2 bakers exposure to the additive, the additive’s
maximum allowable use of 84 IU yeast is approved for use as a food toxicological data, and other relevant
vitamin D2 per 100 g. This category additive as a source of vitamin D2 and information (such as published
would also include other edible plant- as a leavening agent in yeast-leavened literature) available to us. We compare
based beverages made from rice, baked goods and baking mixes and the estimated daily intake (EDI) of the
almond, and coconut, among other yeast-leavened baked snack foods. additive from all food sources to an
foods, that are intended as milk Vitamin D is essential for human acceptable daily intake level established
alternatives. Dean Foods/WhiteWave health. The major function of vitamin D by toxicological data. The EDI is
also requested that we amend § 172.380 is the maintenance of blood serum determined by projections based on the
to allow for the addition of vitamin D3 concentrations of calcium and amount of the additive proposed for use
as a nutrient supplement in milk at phosphorus by enhancing the in particular foods and on data
levels not to exceed 84 IU per 100 g absorption of these minerals in the regarding the amount consumed from
milk. For milk with more than the small intestine. Vitamin D deficiency all food sources of the additive. We
amount of vitamin D provided for in the can lead to abnormalities in calcium commonly use the EDI for the 90th
milk standard of identity in 21 CFR and bone metabolism, such as rickets in percentile consumer of a food additive
131.110(b)(2), the milk would be children or osteomalacia in adults. as a measure of high chronic dietary
Excessive intake of vitamin D elevates intake.
required to be named by use of a
blood plasma calcium levels
nutrient content claim and a A. Acceptable Daily Intake Level for
(hypercalcemia) by increased intestinal
standardized term in accordance with Vitamin D
absorption and/or mobilization from the
21 CFR 130.10. In 2011, the Standing Committee on
bone.
Vitamin D comprises a group of fat- To ensure that vitamin D is not added the Scientific Evaluation of Dietary
soluble seco-sterols and comes in many to the U.S. food supply at levels that Reference Intakes of the Food and
forms. The two major physiologically could raise safety concerns, FDA Nutrition Board at the IOM conducted
relevant forms are vitamin D2 and affirmed vitamin D as GRAS with an extensive review of relevant
vitamin D3. Vitamin D without a specific limitations as listed in published scientific literature on
subscript represents either vitamin D2 or § 184.1950. Under § 184.1(b)(2), an vitamin D to update current dietary
vitamin D3 or both. Vitamin D is ingredient affirmed as GRAS with reference intakes and ULs for vitamin D.
affirmed as generally recognized as safe specific limitations may be used in food Based on this information, the IOM
(GRAS) for use in food as a nutrient only within such limitations, including revised the ULs for vitamin D and
supplement in accordance with 21 CFR the category of food, functional use of developed a report on their findings
184.1950(c)(1) and 21 CFR 184.1(b)(2), the ingredient, and level of use. Any (Ref. 1). In their 2011 assessment of
with the following specific limitations: addition of vitamin D to food beyond vitamin D, the IOM established a UL of
those limitations set out in § 184.1950 1,000 IU per day (IU/p/d) for infants 0
Maximum requires either a food additive months to 6 months of age and a UL of
Category of food levels in food
(as served) regulation or an amendment of 1,500 IU/p/d for infants 6 months to 12
§ 184.1950. months of age. For children 1 year to 3
Breakfast cereals .................. 350 IU/100 To support their petition, Dean years of age, the IOM established a UL
grams (g). Foods/WhiteWave submitted dietary of 2,500 IU/p/d; for children 4 years to
Grain products and pasta ..... 90 IU/100 g. exposure estimates of vitamin D from 8 years of age, the IOM established a UL
Milk ....................................... 42 IU/100 g. the proposed uses of vitamin D2 and of 3,000 IU/p/d. For children 9 years to
Milk products ........................ 89 IU/100 g. vitamin D3, as well as all dietary sources 18 years of age and adults, the IOM
from naturally occurring sources of established a UL of 4,000 IU/p/d.
Additionally, under § 184.1950(c)(2) vitamin D and uses in accordance with The IOM considers the UL as the
and (3), vitamin D is affirmed as GRAS our approved food additive regulations highest average daily intake level of a
for use in infant formulas and (§§ 172.379, 172.380, and 172.381) and nutrient that poses no risk of adverse
margarine, respectively. Under our GRAS affirmation regulation effects when the nutrient is consumed
§ 172.380, vitamin D3 is approved for (§ 184.1950). They also included dietary over long periods of time. The UL is
use as a food additive as a nutrient supplements in their estimates and determined using a risk assessment
supplement in calcium-fortified fruit compared these intake estimates to the model developed specifically for
juices and fruit juice drinks, meal Tolerable Upper Intake Level (UL) for nutrients. The dose-response
replacement and other type bars, soy vitamin D established by the Institute of assessment, which concludes with an
asabaliauskas on DSK3SPTVN1PROD with RULES

protein-based meal replacement Medicine (IOM) of the National estimate of the UL, is built upon three
beverages represented for special dietary Academies. Dean Foods/WhiteWave toxicological concepts commonly used
use in reducing or maintaining body also submitted a number of publications in assessing the risk of exposures to
weight, certain cheese and cheese pertaining to human clinical studies on chemical substances: No-observed-
products, meal replacement beverages vitamin D. Based on this information, adverse-effect level, lowest-observed-
that are not intended for special dietary Dean Foods/WhiteWave concluded that effect level, and application of an
use in reducing or maintaining body the proposed uses of vitamin D2 in uncertainty factor. We considered the
weight, and foods represented for use as edible plant-based beverages intended ULs established by the IOM relative to

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Federal Register / Vol. 81, No. 137 / Monday, July 18, 2016 / Rules and Regulations 46581

Twinbrook Pkwy., Rockville, MD 20852, under the Paperwork Reduction Act of for introduction into interstate
1–800–227–8772, http://www.usp.org/. 1995 is not required. commerce, would not violate section
The current regulation for the use of 301(ll) of the FD&C Act. Furthermore,
VIII. Objections
vitamin D3 in food (§ 172.380) indicates this language is included in all food
that the additive must meet the If you will be adversely affected by additive final rules and therefore should
specifications in the FCC 8. The more one or more provisions of this not be construed to be a statement of the
current FCC is the 9th Edition. The regulation, you may file with the likelihood that section 301(ll) of the
current regulation for vitamin D2 Division of Dockets Management (see FD&C Act applies.
(§ 172.379) indicates the additive must ADDRESSES) either electronic or written
meet the specifications in the 7th objections. You must separately number X. References
edition of the FCC (FCC 7). Because the each objection, and within each References marked with an asterisk
specifications for vitamin D2 and numbered objection you must specify (*) are on display at the Division of
vitamin D3 in FCC 9 are identical to with particularity the provision(s) to Dockets Management (see ADDRESSES),
those in FCC 7 and FCC 8, respectively, which you object, and the grounds for under Docket No. FDA–2013–N–0888,
Dean Foods/WhiteWave requested that your objection. Within each numbered and are available for viewing by
the respective regulations be updated to objection, you must specifically state interested persons between 9 a.m. and 4
reference the specifications in FCC 9. whether you are requesting a hearing on p.m., Monday through Friday; they are
Therefore, we are amending §§ 172.379 the particular provision that you specify also available electronically at http://
and 172.380 by adopting the in that numbered objection. If you do www.regulations.gov. References
specifications for vitamin D2 and not request a hearing for any particular without asterisks are not on display;
vitamin D3 in FCC 9 in place of FCC 7 objection, you waive the right to a they are available as published articles
and FCC 8, respectively. hearing on that objection. If you request and books.
a hearing, your objection must include
IV. Conclusion 1. Committee to Review Dietary Reference
a detailed description and analysis of Intakes for Vitamin D and Calcium, Food
Based on all data relevant to vitamin the specific factual information you and Nutrition Board, Institute of
D that we reviewed, we conclude that intend to present in support of the Medicine, ‘‘Dietary Reference Intakes for
the petitioned uses of vitamin D in milk objection in the event that a hearing is Calcium and Vitamin D,’’ National
and edible plant-based beverages held. If you do not include such a Academies Press, Washington, DC, 2011.
intended as milk alternatives and edible description and analysis for any 2. Taylor, C., K. Patterson, J. Roseland, et al.,
particular objection, you waive the right ‘‘Including Food 25-Hydroxyvitamin D
plant-based yogurt alternatives within
to a hearing on the objection. in Intake Estimates May Reduce the
the limits proposed by Dean Food/ Discrepancy Between Dietary and Serum
WhiteWave are safe. Consequently, we Any objections received in response
Measures of Vitamin D Status,’’ Journal
are amending the food additive to the regulation may be seen in the
of Nutrition, 144:654–659, 2014.
regulations as set forth in this Division of Dockets Management *3. FDA Memorandum from D. Folmer,
document. between 9 a.m. and 4 p.m., Monday CFSAN Chemistry Review Group,
through Friday, and will be posted to Division of Petition Review, to J.
V. Public Disclosure the docket at http:// Kidwell, Regulatory Group I, Division of
In accordance with § 171.1(h) (21 CFR www.regulations.gov. Petition Review, January 27, 2016.
171.1(h)), the petition and the *4. FDA Memorandum from T. Tyler, CFSAN
IX. Section 301(ll) of the Federal Food, Toxicology Team, Division of Petition
documents that we considered and Drug, and Cosmetic Act Review, to J. Kidwell, Division of
relied upon in reaching our decision to
Our review of this petition was Petition Review, February 10, 2016.
approve the petition will be made
available for public disclosure (see FOR limited to section 409 of the Federal List of Subjects in 21 CFR Part 172
FURTHER INFORMATION CONTACT). As Food, Drug, and Cosmetic Act (the
FD&C Act) (21 U.S.C. 348). This final Food additives, Incorporation by
provided in § 171.1(h), we will delete reference, Reporting and recordkeeping
from the documents any materials that rule is not a statement regarding
compliance with other sections of the requirements.
are not available for public disclosure. Therefore, under the Federal Food,
FD&C Act. For example, section 301(ll)
VI. Analysis of Environmental Impact of the FD&C Act (21 U.S.C. 331(ll)) Drug, and Cosmetic Act and under
We previously considered the prohibits the introduction or delivery authority delegated to the Commissioner
environmental effects of this rule, as for introduction into interstate of Food and Drugs and redelegated to
stated in the August 16, 2013, Federal commerce of any food that contains a the Director, Center for Food Safety and
Register document of petition for FAP drug approved under section 505 of the Applied Nutrition, 21 CFR part 172 is
3A4801. We stated that we had FD&C Act (21 U.S.C. 355), a biological amended as follows:
determined, under 21 CFR 25.32(k), that product licensed under section 351 of
the Public Health Service Act (42 U.S.C. PART 172—FOOD ADDITIVES
this action ‘‘is of a type that does not PERMITTED FOR DIRECT ADDITION
individually or cumulatively have a 262), or a drug or biological product for
which substantial clinical investigations TO FOOD FOR HUMAN
significant effect on the human CONSUMPTION
environment’’ such that neither an have been instituted and their existence
environmental assessment nor an has been made public, unless one of the ■ 1. The authority citation for part 172
environmental impact statement is exemptions in section 301(ll)(1) to (4) of continues to read as follows:
asabaliauskas on DSK3SPTVN1PROD with RULES

required. We have not received any new the FD&C Act applies. In our review of
Authority: 21 U.S.C. 321, 341, 342, 348,
information or comments that would this petition, FDA did not consider
371, 379e.
affect our previous determination. whether section 301(ll) of the FD&C Act
or any of its exemptions apply to food ■ 2. Amend § 172.379 by revising the
VII. Paperwork Reduction Act of 1995 containing this additive. Accordingly, first sentence in paragraph (b) and
This final rule contains no collection this final rule should not be construed revising the table in paragraph (c) by
of information. Therefore, clearance by to be a statement that a food containing removing the entry for ‘‘Soy beverages’’
the Office of Management and Budget this additive, if introduced or delivered and adding entries for ‘‘Edible plant-

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Document Created: 2016-07-16 02:28:13
Document Modified: 2016-07-16 02:28:13

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 July 18, 2016. See section VIII for further information on the filing of objections. Submit either electronic or written objections and requests for a hearing by August 17, 2016. The Director of the Federal Register approves the incorporation by reference of certain publications listed in the rule as of July 18, 2016.
Contact		Judith Kidwell, Center for Food Safety and Applied Nutrition (CFSAN) (HFS-265), Food and Drug Administration, 5100 Paint Branch Pkwy., College Park, MD 20740-3835, 240-402-1071.
FR Citation		81 FR 46578

81 FR 46578 - Food Additives Permitted for Direct Addition to Food for Human Consumption; Vitamin D2

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 81, Issue 137 (July 18, 2016)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration