[Federal Register Volume 70, Number 124 (Wednesday, June 29, 2005)]
[Rules and Regulations]
[Pages 37255-37258]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-12699]


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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 D3

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 
D3 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:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.
     Agency Web site: http://www.fda.gov/dockets/ecomments. 
Follow the instructions for submitting comments on the agency Web site.
     E-mail: [email protected]. Include Docket No. 2003F-
0370 in the subject line of your e-mail message.
     FAX: 301-827-6870.
     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 D3 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 D3 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 D3, 
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 D2 and vitamin D3. Vitamin D 
without a subscript represents either D2 or 
D3. Section 184.1950 includes crystalline vitamin 
D2, crystalline vitamin D3, vitamin 
D2 resin, and vitamin D3 resin. Section 
172.380 includes only crystalline vitamin D3.

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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 D3, also known as cholecalciferol, is the 
chemical 9,10-seco(5Z,7E)-5,7,10(19)-cholestatrien-3-ol. Humans 
synthesize vitamin D3 in skin from its precursor, 7-
dehydrocholesterol under exposure to ultraviolet B radiation in 
sunlight. Vitamin D3 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 
D3, 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 D3 
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 D3 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 D3 
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 
D3, Unilever submitted 16 scientific articles published 
subsequent to the IOM report and issuance of the 2003 final rule 
permitting the use of vitamin D3 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 
D3 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 D3 
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 D3 reviewed by the 
agency, FDA concludes that there is a reasonable certainty that no harm 
will result from the use of vitamin D3 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 D3 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 D3 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 
D3 must meet the specifications of the Food Chemicals Codex, 
4th ed., 1996. The agency compared specifications for vitamin 
D3 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 D3.

* * * * *
    (b) Vitamin D3 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