[Federal Register Volume 70, Number 220 (Wednesday, November 16, 2005)]
[Rules and Regulations]
[Pages 69435-69438]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-22670]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 172

[Docket No. 2004F-0374]


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 cheese and cheese products at 
a level above that currently allowed by the regulations. This action is 
in response to a petition filed by Kraft Foods Global, Inc. (Kraft).

DATES: This rule is effective November 16, 2005. Submit written or 
electronic objections and requests for a hearing by December 16, 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. 2004F-0374, by any of the following 
methods:

Electronic Submissions

    Submit electronic objections in the following ways:
     Federal eRulemaking Portal: http://www.regulations.gov.
    Follow the instructions for submitting comments.
     Agency Web site: http://www.fda.gov/dockets/ecomments.

Written Submissions

    Submit written submissions in the following ways:
     FAX: 301-827-6870.
     Mail/Hand delivery/Courier [For paper, disk, or CD-ROM 
submissions]:

[[Page 69436]]

Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    To ensure more timely processing of objections, FDA is no longer 
accepting objections submitted to the agency by e-mail. FDA encourages 
you to continue to submit electronic objections by using the Federal 
eRulemaking Portal or the agency Web site, as described in the 
Electronic Submissions portion of this paragraph.
    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 September 9, 2004 
(69 FR 54687), FDA announced that a food additive petition (FAP 4A4758) 
had been filed by Kraft Foods Global, Inc., c/o Hogan and Hartson, 555 
13th St. NW., Washington, DC 20004. The petition proposed to amend the 
food additive regulations in Sec.  172.380 Vitamin D3 (21 
CFR 172.380) to permit the use of vitamin D3 in cheese and 
cheese products at a level above that permitted in Sec.  184.1950 
Vitamin D (21 CFR 184.1950). Currently, under Sec.  184.1950, milk 
products, which include cheese and cheese products, may be fortified 
with vitamin D at a level up to 89 International Units (IU) per (/) 100 
grams (g). The petitioner requested that the maximum amount of vitamin 
D permitted in certain natural and processed cheeses be increased to 81 
IU vitamin D3/30 g. Cheese and cheese products identified in 
the petition for increased fortification levels are those with a 
reference amount customarily consumed (RACC) of 30 g as defined in 
Sec.  101.12 (21 CFR 101.12), including standardized and 
nonstandardized natural cheese, processed cheese, cream cheese, and 
cheese spreads and dips. Hard grating cheeses with smaller reference 
amounts, such as Parmesan and Romano as defined in Sec. Sec.  133.165 
and 133.183 (21 CFR 133.165 and 133.183), respectively, and those 
defined by the standards of identity in Sec.  133.148 (21 CFR 133.148), 
are not included, nor are cheeses with larger reference amounts, such 
as cottage cheese or ricotta cheese. Cheese-like products made from 
nondairy starting materials (e.g., soy-based products) are not 
considered to be cheese and are not included. The new limit would 
permit vitamin D to be added to cheese and cheese products at a level 
slightly more than 20 percent of the reference daily intake (RDI) of 
vitamin D/30 g serving. Under Sec.  101.54 (21 CFR 101.54), food 
containing 10 to 19 percent of the RDI of a nutrient is allowed to 
carry a label claim such as ``good source'' and if the level is 20 
percent or more of the RDI, the food label may claim ``excellent 
source.''
    Under Sec.  172.380, vitamin D3 is approved for use as a 
nutrient supplement in calcium-fortified fruit juices, calcium-
fortified fruit juice drinks, meal replacement and other-type bars, and 
soy-protein based meal replacement beverages represented for special 
dietary use in reducing or maintaining body weight. Vitamin D \1\, 
including vitamin D3, also is affirmed as generally 
recognized as safe (GRAS) for use in food under Sec.  184.1950 with the 
following limitations:
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    \1\Vitamin D comprises a group of fat-souble 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. As used in Sec.  184.1950, the meaning of the term 
vitamin D 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 cereals                    350 IU/100 g
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Grain products and pasta             90 IU/100 g
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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. 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 to maintain blood serum concentrations of calcium and 
phosphorus by enhancing the absorption of these minerals from 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, functional use, 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 the safety of the proposed uses of vitamin 
D3, Kraft submitted dietary intake estimates from current 
and proposed uses and from naturally-occurring sources of vitamin D 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. Kraft 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 
cheese and cheese products 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 intake of the additive, the additive's 
toxicological data, and other

[[Page 69437]]

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 amount consumed from all sources of the additive. 
The agency commonly uses the EDI for the 90\th\ percentile consumer of 
a food additive as a measure of high chronic dietary intake.

A. Estimated Daily Intake for Vitamin D

    The petitioner provided mean and 90\th\ percentile vitamin D intake 
estimates for consumers of cheese and cheese products from the 
following: (1) The proposed food uses; (2) current regulated food uses 
(including naturally occurring sources of vitamin D); and (3) dietary 
supplements.\2\ Intake estimates for the U.S. population 2 years of age 
and older were provided, as well as estimates for 18 population 
subgroups, including breast-fed and nonbreast-fed infants 0 to 11 
months of age. The agency agrees with the methodology used to calculate 
these estimates, with the exception of intake estimates from dietary 
supplements for infants 0 to 11 months of age.
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    \2\ The intake estimate included Parmesan cheese; however, 
fortification of hard grating cheeses such as Parmesan was not 
requested.
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    For consumers 2 years of age and older, Kraft estimated mean and 
90\th\ percentile dietary intakes from current (including naturally 
occurring sources) and proposed food uses of vitamin D to be 335 IU per 
person per day (IU/p/d) and 582 IU/p/d, respectively. For breast-fed 
infants 0 to 11 months of age, mean and 90\th\ percentile intakes were 
estimated to be 180 IU/p/d and 322 IU/p/d, respectively. For nonbreast-
fed infants 0 to 11 months of age, mean and 90\th\ percentile intakes 
were estimated to be 443 IU/p/d and 696 IU/p/d, respectively. For 
children 1 to 3 years of age, mean and 90\th\ percentile intake 
estimates were 383 IU/p/d and 583 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 33 percent of the U.S. 
population 2 years 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 
conventional food, Kraft considered it appropriate to assume that 
consumers of cheese and cheese products who take dietary supplements 
likely would take dietary supplements containing 400 IU of vitamin D. 
They then added this value to the mean and 90\th\ percentile intake 
estimates from current and proposed food uses for consumers 2 years of 
age and older. For consumers of cheese and cheese products, mean and 
90\th\ percentile dietary intakes from current and proposed food uses 
and dietary supplements were estimated to be 735 IU/p/d and 982 IU/p/d, 
respectively, for consumers 2 years of age and older. Kraft chose not 
to add a value of 400 IU from supplement use to intake estimates for 
infants 0 to 11 months of age due to the low percentage of infants 
reported to use supplements (7 percent) in the NHANES III study. While 
we do not agree with Kraft's choice to exclude supplement use in the 
vitamin D intake for infants, we believe that, in light of recent 
recommendations from the American Academy of Pediatrics (AAP),\3\ 
estimating a supplement intake of 200 IU/p/d is more appropriate than 
400 IU/p/d for infants.
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    \3\ ``Prevention of Rickets and Vitamin D Deficiency: New 
Guidelines for Vitamin D Intake,'' from the American Academy of 
Pediatrics in: Pediatrics Vol. III No. 4, pp. 908-910, April 2003. 
The AAP recommends a daily vitamin D supplement of 200 IU for the 
following groups:
     All breast-fed infants unless they are weaned to at 
least 500 milliliter (mL)/d of vitamin D-fortified formula or milk.
     All nonbreast-fed infants who are ingesting less than 
500 mL/d of vitamin D-fortified formula or milk.
     Children and adolescents who do not get regular 
sunlight exposure, do not ingest at least 500 mL/d of vitamin D-
fortified milk, or do not take a daily multivitamin supplement 
containing at least 200 IU of vitamin D.
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    Based on AAP recommendations, the agency assumed a vitamin D intake 
of 200 IU from supplement use for infants 0 to 11 months of age, 
resulting in exposure estimates at the 90th percentile of 522 IU/p/d 
and 896 IU/p/d for breast-fed and nonbreast-fed infants, respectively. 
For all other populations (including children and adolescents) we 
assumed a supplement intake of 400 IU/p/d (Ref. 1).

B. Acceptable Daily Intake for Vitamin D

    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/p/d. The UL for infants less than 1 year of age is 1,000 IU/p/
d.
    The IOM considers the UL as the highest daily intake level of a 
nutrient that is unlikely to pose a 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.

C. Safety Assessment

    To support the safety of their proposed uses for vitamin 
D3, Kraft submitted scientific articles published subsequent 
to the IOM report and issuance of the February 2003 final rule for the 
use of vitamin D3 in calcium-fortified fruit juices and 
fruit juice drinks (68 FR 9000, February 27, 2003), including 12 
clinical studies in humans in which subjects received both vitamin D 
and calcium supplementation for periods of up to 3 years. Kraft 
concluded that the recent publications continue to support the safe use 
of vitamin D supplementation in both animals and humans. FDA concurs 
with Kraft's conclusions.
    FDA considered the UL established by IOM for infants, 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 cheese and cheese products. For all children 
and adults 2 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. For infants 0 to 11 months of age, 
mean and 90\th\ percentile intakes are below the UL of 1000 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 proposed use as 
a nutrient supplement in cheese and cheese products will not pose a 
safety concern.

[[Page 69438]]

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 cheese and cheese products, excluding cottage cheese, 
ricotta cheese, and hard grating cheeses, such as Parmesan and Romano 
as defined in Sec. Sec.  133.165 and 133.183, respectively, and those 
defined by the standard of identity in Sec.  133.148, at levels up to 
81 IU/30 g of cheese. Thus, vitamin D3 is safe for the 
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 Sec.  172.380.
    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 4A4758. 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. For 
written objections, three copies of all documents shall be submitted 
and shall 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.

VII. Reference

    The following reference has been placed on display at 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.
    1. Memorandum from Folmer, Division of Petition Review, 
Chemistry Review Group, to Kidwell, Division of Petition Review, 
February 2, 2005.

List of Subjects in 21 CFR Part 172

    Food additives, 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 adding paragraph (c)(5) to read as 
follows:


Sec.  172.380  Vitamin D3.

* * * * *
    (c) * * *
    (5) At levels not to exceed 81 IU per 30 grams in cheese and cheese 
products as defined under Sec.  170.3(n)(5) of this chapter, excluding 
cottage cheese, ricotta cheese, and hard grating cheeses such as 
Parmesan and Romano as defined in Sec. Sec.  133.165 and 133.183 of 
this chapter, and those defined by standard of identity in Sec.  
133.148 of this chapter.

    Dated: November 4, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-22670 Filed 11-15-05; 8:45 am]
BILLING CODE 4160-01-S