[Federal Register: November 16, 2005 (Volume 70, Number 220)]
[Rules and Regulations]
[Page 69435-69438]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr16no05-8]
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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 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 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:
<bullet> Federal eRulemaking Portal:
http://www.regulations.gov.
Follow the instructions for submitting comments.
<bullet> Agency Web site:
http://www.fda.gov/dockets/ecomments.
Written Submissions
Submit written submissions in the following ways:
<bullet> FAX: 301-827-6870.
<bullet> 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 D
3 (21
CFR 172.380) to permit the use of vitamin D
3 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 D
3/30 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 D
3 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 D
3, 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 D
2 and vitamin D
3. Vitamin D
without a subscript represents either D
2 or
D
3. As used in Sec. 184.1950, the meaning of the term
vitamin D 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 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 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. 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
D
3, 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 D
3 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:
<bullet> All breast-fed infants unless they are weaned to at
least 500 milliliter (mL)/d of vitamin D-fortified formula or milk.
<bullet> All nonbreast-fed infants who are ingesting less than
500 mL/d of vitamin D-fortified formula or milk.
<bullet> 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
D
3, Kraft submitted scientific articles published subsequent
to the IOM report and issuance of the February 2003 final rule for the
use of vitamin D
3 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 D
3 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 D
3 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 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 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 D
3 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 D
3 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 D
3.
* * * * *
(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
