[Federal Register: June 29, 2005 (Volume 70, Number 124)]
[Rules and Regulations]
[Page 37255-37258]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr29jn05-3]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 172
[Docket No. 2003F-0370]
Food Additives Permitted for Direct Addition to Food for Human
Consumption; Vitamin D
3
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is amending the food
additive regulations to provide for the safe use of vitamin
D
3 as a nutrient supplement in meal replacement bars, other-
type bars, and soy-protein based meal replacement beverages represented
for special dietary use in reducing or maintaining body weight. This
action is in response to a petition filed by Unilever United States,
Inc. (Unilever).
DATES: This rule is effective June 29, 2005. The Director of the Office
of the Federal Register approves the incorporation by reference in
accordance with 5 U.S.C. 552(a) and 1 CFR part 51 of certain
publications in 21 CFR 172.380 as of June 29, 2005. Submit written or
electronic objections and requests for a hearing by July 29, 2005. See
section VI of this document for information on the filing of
objections.
ADDRESSES: You may submit written objections and requests for a
hearing, identified by Docket No. 2003F-0370, by any of the following
methods:
<bullet> Federal eRulemaking Portal:
http://www.regulations.gov.
Follow the instructions for submitting comments.
<bullet> Agency Web site:
http://www.fda.gov/dockets/ecomments.
Follow the instructions for submitting comments on the agency Web site.
<bullet> E-mail:
fdadockets@oc.fda.gov. Include Docket No. 2003F-
0370 in the subject line of your e-mail message.
<bullet> FAX: 301-827-6870.
<bullet> Mail/Hand delivery/Courier [For paper, disk, or CD-ROM
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 agency name
and docket number for this rulemaking. All objections received will be
posted without change to
http://www.fda.gov/ohrms/dockets/default.htm,
including any personal information provided. For detailed instructions
on submitting objections, see the ``Objections'' heading of the
SUPPLEMENTARY INFORMATION section of this document.
Docket: For access to the docket to read background documents or
objections received, go to
http://www.fda.gov/ohrms/dockets/default.htm
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 L. Kidwell, Center for Food
Safety and Applied Nutrition (HFS-265), Food and Drug Administration,
5100 Paint Branch Pkwy., College Park, MD 20740, 301-436-1071.
SUPPLEMENTARY INFORMATION:
I. Introduction
In a notice published in the Federal Register of August 21, 2003
(68 FR 50541), FDA announced that a food additive petition (FAP 3A4746)
had been filed by Unilever United States, Inc., 390 Park Ave., New
York, NY 10022-4698. The petition proposed that the food additive
regulations be amended in Sec. 172.380 Vitamin D3 (21 CFR 172.380) to
provide for the safe use of vitamin D
3 as a nutrient
supplement in certain foods for special dietary use, such as meal
replacement products and snack replacement products. Foods specifically
identified in the petition were meal replacement bars, other-type bars,
and soy-protein based meal replacement beverages that are represented
for special dietary use in reducing or maintaining body weight.
Vitamin D
3 currently is approved for use as a nutrient
supplement in calcium-fortified fruit juice and fruit juice drinks
under Sec. 172.380. Vitamin D\1\, including vitamin D
3,
also is affirmed as generally recognized as safe (GRAS) for use in food
under Sec. 184.1950 (21 CFR 184.1950) with the following limitations:
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\1\ Vitamin D comprises a group of fat-soluble seco-sterols and
comes in many forms. The two major physiologically relevant forms
are vitamin D
2 and vitamin D
3. Vitamin D
without a subscript represents either D
2 or
D
3. Section 184.1950 includes crystalline vitamin
D
2, crystalline vitamin D
3, vitamin
D
2 resin, and vitamin D
3 resin. Section
172.380 includes only crystalline vitamin D
3.
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Category of Food Maximum Levels in Food (as served)
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Breakfast 350 International Units (IU)/100 grams (g)
cereals
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Grain products 90 IU/100 g
and pasta
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[[Page 37256]]
Milk 42 IU/100 g
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Milk products 89 IU/100 g
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Additionally, under Sec. 184.1950(c)(2) and (c)(3) vitamin D is
affirmed as GRAS for use in infant formula and margarine, respectively.
Vitamin D
3, also known as cholecalciferol, is the
chemical 9,10-seco(5Z,7E)-5,7,10(19)-cholestatrien-3-ol. Humans
synthesize vitamin D
3 in skin from its precursor, 7-
dehydrocholesterol under exposure to ultraviolet B radiation in
sunlight. Vitamin D
3 does not accumulate significantly in
the body as a result of sun exposure because it is metabolized and
removed during normal skin cell turnover. Other sources of naturally
occurring vitamin D are foods such as butter, buttermilk, cheese,
cream, eggs, fish, goat milk, meat fats and organ meats, and mushrooms.
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. At high levels, vitamin D may be toxic. Excessive intake of
vitamin D elevates blood plasma calcium levels 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 21 CFR
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(s), functional use(s), and level(s) 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 the safety of the proposed uses of vitamin
D
3, Unilever submitted dietary intake estimates from current
and proposed uses and naturally occurring sources of vitamin D and
compared these exposure estimates to the tolerable upper intake level
(UL) for vitamin D established by the Institute of Medicine (IOM) of
the National Academies. The petitioner also submitted a number of
publications pertaining to human clinical studies on vitamin D. Based
on this information, which is discussed in section II of this document,
the petitioner concluded that the proposed use of vitamin D
3
in meal replacement bars and other-type bars represented for special
dietary use in reducing or maintaining body weight at levels not to
exceed 100 IU per 40 g product is safe. The petitioner also concluded
that the proposed use of vitamin D
3 in soy-protein based
meal replacement beverages represented for special dietary use in
reducing or maintaining body weight at levels not to exceed 140 IU per
240 milliliter product is safe.
II. Evaluation of Safety
To establish with reasonable certainty that a food additive is not
harmful under its intended conditions of use, FDA considers the
projected human dietary exposure to the additive, the additive's
toxicological data, and other relevant information (such as published
literature) available to the agency. FDA compares an individual's
estimated daily intake (EDI) of the additive from all sources to an
acceptable 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 consumption
levels from all sources of the additive.
A. Acceptable Daily Intake for Vitamin D for Adults and Children
In 1997, the Standing Committee on the Scientific Evaluation of
Dietary Reference Intakes of the Food and Nutrition Board at IOM
conducted an extensive review of toxicology and metabolism studies on
vitamin D published through 1996. The IOM published a detailed report
that included a UL for vitamin D for infants, children, and adults. The
IOM UL for vitamin D for children 1 to 18 years of age and adults is
2,000 IU per person per day (IU/p/d). The UL for infants is 1,000 IU/p/
d.
The IOM considers the UL as the highest usual 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 and considers
intake from all sources: 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.
B. Estimated Daily Intake for Vitamin D
The petitioner provided average and 90th percentile vitamin D
intake estimates for consumers of meal replacement bars, other-type
bars, and soy-protein based meal replacement beverages represented for
special dietary use from the following: (1) The proposed food uses, (2)
current food uses (including naturally occurring sources of vitamin D),
(3) current and proposed food uses, and (4) current and proposed food
uses and dietary supplements. The proposed uses are for foods intended
for use by adults as part of a weight control diet. Although these
special dietary foods are not intended for use by children, the
petitioner acknowledged that some sporadic use by children may occur,
especially among older children. Therefore, intake estimates for adults
and children over the age of 9 years were provided. The agency has
determined that the methodology used to calculate these estimates is
appropriate.
For the proposed food uses, dietary intake of vitamin D
3
for 90th percentile consumers of meal replacement bars, other-type
bars, and soy-protein based meal replacement beverages was estimated to
be 215 IU/p/d for consumers 9 years of age and older. The corresponding
mean intake was estimated to be 127 IU/p/d.
For currently regulated uses in conventional foods (under Sec.
184.1950 and Sec. 172.380) and naturally occurring sources, mean
dietary exposure to vitamin D for consumers of meal replacement bars,
other-type bars, and soy-protein based meal replacement beverages was
estimated to be 470 IU/p/d for consumers 9 years of age and older.
Intake at the 90th percentile was estimated to be 957 IU/p/d. For
consumers 9 years of age and older, mean and 90th percentile dietary
intakes from current (including naturally occurring sources) and
proposed food uses of vitamin D were estimated to be 565 IU/p/d and 995
IU/p/d, respectively.
The petitioner also considered the intake of vitamin D from dietary
supplements. The National Health and Nutrition Examination Survey III
(NHANES III) data indicate that approximately 40 percent of the U.S.
population 2 months of age and older take dietary supplements. The
NHANES III data also show that, when vitamin D is taken as a dietary
supplement, the most frequent level is 400 IU/p/d. As a conservative
estimate of intake of vitamin D from dietary supplements and
[[Page 37257]]
food uses, the petitioner assumed that all consumers of meal
replacement bars, other-type bars, and soy-protein based meal
replacement beverages represented for special dietary use would take
dietary supplements containing 400 IU of vitamin D. They then added
this value to the mean and 90th percentile intake estimates from
current and proposed food uses. For consumers of meal replacement bars,
other-type bars, and soy-protein based meal replacement beverages, mean
and 90th percentile dietary intakes from current and proposed food uses
and dietary supplements were estimated to be 965 IU/p/d and 1,395 IU/p/
d for consumers 9 years of age and older, respectively. FDA concurs
with these exposure estimates.
C. Safety Assessment
To support the safety of their proposed uses for vitamin
D
3, Unilever submitted 16 scientific articles published
subsequent to the IOM report and issuance of the 2003 final rule
permitting the use of vitamin D
3 in calcium-fortified fruit
juices and fruit juice drinks within the prescribed limitations (68 FR
9000, February 27, 2003). Unilever concluded that the recent
publications continue to support the safe use of vitamin D
supplementation in both animals and humans. FDA concurs with Unilever's
conclusions.
FDA considered the UL established by IOM for children and adults
relative to the intake estimates provided by the petitioner as the
primary basis for assessing the safety of the proposed use of vitamin
D
3 in meal replacement bars, other-type bars, and soy-
protein based meal replacement beverages represented for special
dietary use. For all children and adults 9 years of age and older, mean
and 90th percentile intake estimates from current and proposed food
uses of vitamin D are well below the IOM UL of 2,000 IU/p/d.
Additionally, when dietary supplements are included in the
calculations, intake estimates remain below the UL.
Because the EDI of vitamin D from all sources is less than the UL,
the agency concludes that dietary exposure of vitamin D
3
from its use as a nutrient supplement in meal replacement bars, other-
type bars, and soy-protein based meal replacement beverages represented
for special dietary use in reducing or maintaining body weight will not
pose a safety concern.
III. Conclusion
Based on all data relevant to vitamin D
3 reviewed by the
agency, FDA concludes that there is a reasonable certainty that no harm
will result from the use of vitamin D
3 as a nutrient
supplement in meal replacement bars, other-type bars, and soy-protein
based meal replacement beverages represented for special dietary use in
reducing or maintaining body weight. Thus, vitamin D
3 is
safe for its proposed use and the agency concludes that the food
additive regulations should be amended as set forth in this document.
To ensure that only food grade vitamin D
3 is used in food,
the additive must meet the specifications set forth in this document.
Based on a request by the petitioner, FDA also is updating Sec.
172.380 by citing the 5th edition of the Food Chemicals Codex rather
than the 4th edition. Section 172.380(b) currently states that vitamin
D
3 must meet the specifications of the Food Chemicals Codex,
4th ed., 1996. The agency compared specifications for vitamin
D
3 in the 4th and 5th editions and found them to be
identical. Therefore, the agency is making this requested editorial
change. In addition, the agency is making an editorial update to Sec.
172.380(b) to reflect the new address for the National Academy Press.
The agency also is making editorial changes to Sec. 172.380(c) for
clarification.
In accordance with Sec. 171.1(h) (21 CFR 171.1(h)), the petition
and the documents that FDA considered and relied upon in reaching its
decision to approve the petition are available for inspection at the
Center for Food Safety and Applied Nutrition by appointment with the
information contact person (see FOR FURTHER INFORMATION CONTACT). As
provided in Sec. 171.1(h), the agency will delete from the documents
any materials that are not available for public disclosure before
making the documents available for inspection.
IV. Environmental Effects
The agency has previously considered the environmental effects of
this rule as announced in the notice of filing for FAP 3A4746 (68 FR
50541). No new information or comments have been received that would
affect the agency's previous determination that there is no significant
impact on the human environment and that an environmental impact
statement is not required.
V. 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.
VI. Objections
Any person who will be adversely affected by this regulation may
file with the Division of Dockets Management (see ADDRESSES) written or
electronic objections. Each objection shall be separately numbered, and
each numbered objection shall specify with particularity the provisions
of the regulation to which objection is made and the grounds for the
objection. Each numbered objection on which a hearing is requested
shall specifically so state. Failure to request a hearing for any
particular objection shall constitute a waiver of the right to a
hearing on that objection. Each numbered objection for which a hearing
is requested shall include a detailed description and analysis of the
specific factual information intended to be presented in support of the
objection in the event that a hearing is held. Failure to include such
a description and analysis for any particular objection shall
constitute a waiver of the right to a hearing on the objection. Three
copies of all documents are to be submitted and are to be identified
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.
List of Subjects in 21 CFR Part 172
Food additives, Incorporation by reference, Reporting and
recordkeeping requirements.
0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 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 21 CFR part 172 continues to read as
follows:
Authority: 21 U.S.C. 321, 341, 342, 348, 371, 379e.
0
2. Section 172.380 is amended by revising paragraphs (b) and (c) and
removing paragraph (d) to read as follows:
Sec. 172.380 Vitamin D
3.
* * * * *
(b) Vitamin D
3 meets the specifications of the Food
Chemicals Codex, 5th ed. (2004), pp. 498-499, which is incorporated by
reference. The Director of the Office of the Federal Register approves
this incorporation by
[[Page 37258]]
reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may
obtain copies from the National Academy Press, 500 Fifth St. NW.,
Washington, DC 20001 (Internet address
http://www.nap.edu). Copies may
be examined at the Center for Food Safety and Applied Nutrition's
Library, Food and Drug Administration, 5100 Paint Branch Pkwy., College
Park, MD 20740, or at the National Archives and Records Administration
(NARA). For information on the availability of this material at NARA,
call 202-741-6030, or go to:
http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html
.
(c) The additive may be used as follows:
(1) At levels not to exceed 100 International Units (IU) per 240
milliliters (mL) in 100 percent fruit juices (as defined under Sec.
170.3(n)(35) of this chapter) that are fortified with greater than or
equal to 33 percent of the reference daily intake (RDI) of calcium per
240 mL, excluding fruit juices that are specially formulated or
processed for infants.
(2) At levels not to exceed 100 IU per 240 mL in fruit juice drinks
(as defined under Sec. 170.3(n)(35) of this chapter) that are
fortified with greater than or equal to 10 percent of the RDI of
calcium per 240 mL, excluding fruit juice drinks that are specially
formulated or processed for infants.
(3) At levels not to exceed 140 IU per 240 mL (prepared beverage)
in soy-protein based meal replacement beverages (powder or liquid) that
are represented for special dietary use in reducing or maintaining body
weight in accordance with Sec. 105.66 of this chapter.
(4) At levels not to exceed 100 IU per 40 grams in meal replacement
bars or other-type bars that are represented for special dietary use in
reducing or maintaining body weight in accordance with Sec. 105.66 of
this chapter.
Dated: June 20, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-12699 Filed 6- 28-05; 8:45 am]
BILLING CODE 4160-01-S
