
[Federal Register Volume 77, Number 168 (Wednesday, August 29, 2012)]
[Rules and Regulations]
[Pages 52228-52232]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-21353]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 172

[Docket No. FDA-2009-F-0570]


Food Additives Permitted for Direct Addition to Food for Human 
Consumption; Vitamin D2 Bakers Yeast

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 
D2 bakers yeast as a source of vitamin D2 and as 
a leavening agent in yeast-leavened baked products at levels not to 
exceed 400 International Units (IU) of vitamin D2 per 100 
grams (g) in the finished food. This action is in response to a 
petition filed by Lallemand, Inc. (Lallemand).

DATES: This rule is effective August 29, 2012. Submit either electronic 
or written objections and requests for a hearing by September 28, 2012. 
See section VII of this document for information on filing objections.

[[Page 52229]]


ADDRESSES: You may submit either electronic or written objections and 
requests for a hearing, identified by Docket No. FDA-2009-F-0570, by 
any of the following methods:

Electronic Submissions

    Submit electronic objections in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.

Written Submissions

    Submit written objections in the following ways:
     FAX: 301-827-6870.
     Mail/Hand delivery/Courier (for paper 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 No. FDA-2009-F-0570. All objections received will be posted 
without change to http://www.regulations.gov, 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.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 (HFS-265), Food and Drug Administration, 5100 
Paint Branch Pkwy, College Park, MD 20740, 240-402-1071.

SUPPLEMENTARY INFORMATION:

I. Introduction

    In a notice published in the Federal Register of December 17, 2009 
(74 FR 66979), FDA announced that a food additive petition (FAP 9A4779) 
had been filed by Lallemand, Inc., c/o Dennis T. Gordon, 117 N. Welcome 
Slough Rd., Puget Island, Cathlamet, WA 98612. The petition proposed to 
amend the food additive regulations in part 172--Food Additives 
Permitted for Direct Addition to Food for Human Consumption (21 CFR 
part 172), to provide for the safe use of vitamin D2 bakers 
yeast as a dual purpose nutrient supplement and leavening agent or 
dough relaxer in yeast-containing baked products at levels not to 
exceed 400 IU of vitamin D2 per 100 g in the finished food. 
The specific foods identified by the petition in which the additive 
will be used are yeast-leavened baked goods and baking mixes and yeast-
leavened baked snack foods. After the notice was published, Lallemand 
amended the petition to exclude the proposed use of the additive as a 
dough relaxer.
    Vitamin D,\1\ including Vitamin D2, is affirmed as 
generally recognized as safe (GRAS) for use in food as a nutrient 
supplement in Sec.  184.1950(c)(1) (21 CFR 184.1950(c)(1)) in 
accordance with Sec.  184.1(b)(2) (21 CFR 184.1(b)(2)), with the 
following specific 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 vitamin D2 or 
vitamin D3.

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                                           Maximum levels in food  (as
            Category of food                         served)
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Breakfast cereals......................  350 IU/100 g.
Grain products and pasta...............  90 IU/100 g.
Milk...................................  42 IU/100 g.
Milk products..........................  89 IU/100 g.
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    Additionally, under Sec. Sec.  184.1950(c)(2) and (c)(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 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; and cheese and cheese products as 
defined therein. Under Sec.  172.379, vitamin D2 is approved 
for use 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.
    Vitamin D2, also known as ergocalciferol, is the 
chemical 9,10-seco(5Z,7E,22E)-5,7,10(19),22-ergostatetraen-3-ol. The 
additive that is the subject of this petition is vitamin D2 
bakers yeast that is produced by exposing bakers yeast (Saccharomyces 
cerevisiae) to ultraviolet (UV) light, resulting in increased 
conversion of endogenous ergosterol to ergocalciferol. The vitamin 
D2 in the UV light-treated bakers yeast is the same 
substance affirmed as GRAS in Sec.  184.1950 and approved for use as a 
nutrient supplement in Sec.  172.379.
    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 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, 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 D2 
bakers yeast, Lallemand performed analyses for the presence of any 
potential toxic precursor sterol components in UV light-treated bakers 
yeast. In addition, Lallemand submitted dietary intake estimates of 
vitamin D from the proposed uses of vitamin D2 bakers yeast, 
currently-regulated uses of vitamin D, and from naturally-occurring 
sources of vitamin D. They 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. Lallemand 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, Lallemand concluded that the proposed uses of 
vitamin D2 bakers yeast in yeast-leavened baked products are 
safe.

II. Evaluation of Safety

A. UV Light-Treated Bakers Yeast

    To support the safety of UV light-treated bakers yeast, Lallemand 
performed analyses to demonstrate that UV light treatment of bakers 
yeast does not produce additional sterols of toxicological concern. 
Lallemand provided chromatograms of extracts of UV light-treated and 
non-UV light-treated bakers yeast, and identified the substances 
present in the yeast extracts. One of the substances identified, 
tachysterol, is a photoisomer resulting from UV light treatment of the 
vitamin D precursor, pre-vitamin D. Tachysterol is a biologically 
inactive pre-vitamin form of vitamin D. Lallemand

[[Page 52230]]

concluded that the small amount of tachysterol present in vitamin 
D2 bakers yeast was insignificant and did not pose a 
toxicological concern.
    A second photoisomer, lumisterol, is also typically formed from UV 
light treatment of pre-vitamin D. Lallemand reported that they did not 
detect lumisterol in the UV light-treated samples. Because tachysterol 
is reported as the predominant photoisomer produced at the UV 
wavelength used to make vitamin D2 bakers yeast, it is 
reasonable that lumisterol would not be present at a detectable amount.
    Other substances identified from the chromatograms were pre-vitamin 
D2 (nonactive form of vitamin D2), vitamin 
D2, and ergosterol (naturally present in yeast). No other 
substances related to UV light treatment of bakers yeast were observed.

B. Vitamin D

    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 relevant information (such as published 
literature) available to the Agency. FDA compares an individual's 
estimated daily intake (EDI) of the additive from all food 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 food sources of the additive. The Agency commonly 
uses the EDI for the 90th percentile consumer of a food additive as a 
measure of high chronic dietary intake.
1. Estimated Daily Intake for Vitamin D
    Lallemand provided mean and 90th percentile vitamin D intake 
estimates for consumers of yeast-leavened baked products from: (1) The 
proposed food uses of vitamin D2 bakers yeast; (2) current 
food uses of vitamin D (including regulated uses, naturally-occurring 
sources of vitamin D, and dietary supplements); and (3) combined 
current and proposed food uses. Lallemand provided intake estimates for 
the overall U.S. population (1 year of age and older) and nine 
population subgroups (including infants less than 12 months of age). 
The Agency has determined that the methodology used to calculate these 
estimates is appropriate.
    Lallemand's estimate of intake of vitamin D from all food sources 
for the overall U.S. population (1 year of age and older), including 
consumers of the yeast-leavened baked products identified in the 
petition, was 1,670 IU per person per day (IU/p/d) for the 90th 
percentile consumer. For the population subgroup of infants less than 
12 months of age, including consumers of the yeast-leavened baked 
products identified in the petition, the dietary intake of vitamin D 
from all food sources was estimated to be 969 IU/p/d for the 90th 
percentile consumer. FDA concurs with these intake estimates.
2. Acceptable Intake Level for Vitamin D
    In 1997, 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 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. At 
that time, the IOM established a UL for vitamin D of 2,000 IU/per day 
(p/d) for children 1 to 18 years of age and adults. The UL for all 
infants was 1,000 IU/p/d.
    More recently, 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 more recent 
information, the IOM revised the ULs for vitamin D and developed a 
report on their findings.\2\ In their current assessment of vitamin D, 
the IOM determined a UL of 1,000 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 UL was 
determined to be 2,500 IU/p/d; for children 4 years to 8 years of age, 
the UL was determined to be 3,000 IU/p/d. For children 9 years to 18 
years of age and adults, the UL was determined to be 4,000 IU/p/d.
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    \2\ 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.
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    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.

C. Safety Assessment

    FDA reviewed and evaluated the information submitted by Lallemand 
regarding the safety of UV light-treated bakers yeast. FDA concludes 
that the use of UV light-treated bakers yeast does not pose a safety 
concern, since the UV light treatment has been shown not to produce any 
new components of toxicological concern that could be introduced into 
the diet (see section II.A of this document).
    In addition, FDA reviewed and evaluated the information submitted 
by Lallemand regarding the safety of the dietary intake of vitamin 
D2 that would result from the proposed uses of vitamin 
D2 bakers yeast. Lallemand submitted scientific articles 
published subsequent to the 1997 IOM report and issuance of the March 
16, 2009, final rule (74 FR 11019) for the use of vitamin D2 
in soy-based food products. Lallemand concluded that these recent 
publications continue to support vitamin D supplementation in humans. 
FDA concurs with Lallemand's conclusion.
    FDA considered the ULs established by the IOM relative to the 
intake estimates provided by Lallemand as the primary basis for 
assessing the safety of petitioned uses of vitamin D. FDA also reviewed 
the scientific articles submitted by Lallemand. Finally, FDA reviewed 
studies on vitamin D that have published since the Agency's evaluation 
of four previous food additive petitions for fortifying a variety of 
foods with vitamin D. The most recent petition resulted in FDA's 
amendment of the food additive regulations in Sec.  172.379 to allow 
for the safe use of vitamin D2 as a nutrient supplement in 
soy-based food products (74 FR 11019, March 16, 2009). The three 
earlier food additive petitions also resulted in amendments of the food 
additive regulations to allow for the safe use of vitamin D3 
as a nutrient supplement in certain foods (70 FR 69435, November 16, 
2005; 70 FR 37255, June 29, 2005; 70 FR 36021, June 22, 2005; and 68 FR 
9000, February 27, 2003).
    Depending on the age group, the IOM ULs for the U.S. population 1 
year of age and older range from 2,500 IU/p/d to 4,000 IU/p/d. The 
estimated intake of vitamin D from all food sources, including the 
proposed uses, at the 90th percentile for the overall U.S. population 
(1 year of age and older) is estimated to be 1,670 IU/p/d, which is 
below the lowest IOM UL in the range of ULs for the overall U.S. 
population (1 year of age and older). For infants less

[[Page 52231]]

than 12 months of age, the estimated intake of vitamin D from all food 
sources, including the proposed uses, at the 90th percentile is 969 IU/
p/d, which is below both the IOM UL of 1,000 IU/p/d for infants 0 
months to 6 months of age and the IOM UL of 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 calculated for each 
population group is less than the corresponding IOM UL for that 
population group, the Agency concludes that dietary intake of vitamin 
D2 bakers yeast from its proposed uses as a source of 
vitamin D2 and as a leavening agent in yeast-leavened baked 
products will not pose a safety concern.

III. Conclusion

    Based on all data relevant to vitamin D2 bakers yeast 
reviewed by the Agency, FDA concludes that there is a reasonable 
certainty that no harm will result from the use of vitamin 
D2 bakers yeast as a source of vitamin D2 and as 
a leavening agent in yeast-leavened baked products within the limits 
proposed by Lallemand. Thus, vitamin D2 bakers yeast is safe 
for the proposed uses, and the Agency concludes that the food additive 
regulations should be amended as set forth in this document.

IV. Public Disclosure

    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 will be made 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.

V. Environmental Impact

    The Agency has previously considered the environmental effects of 
this rule as announced in the notice of filing for FAP 9A4779 (74 FR 
66979). 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.

VI. 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.

VII. Objections

    Any person who will be adversely affected by this regulation may 
file with the Division of Dockets Management (see ADDRESSES) either 
electronic or written objections. Each objection must be separately 
numbered, and each numbered objection must 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 must specifically so state. Failure to request a hearing 
for any particular objection constitutes a waiver of the right to a 
hearing on that objection. Each numbered objection for which a hearing 
is requested must 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 constitutes a 
waiver of the right to a hearing on the objection. It is only necessary 
to send one set of documents. Identify documents 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.

VIII. Section 301(ll) of the Federal Food, Drug, and Cosmetic Act (FD&C 
Act)

    FDA's review of this petition was limited to section 409 of 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, the Food 
and Drug Administration Amendments Act of 2007, which was signed into 
law on September 27, 2007, amended the FD&C Act to, among other things, 
add section 301(ll) (21 U.S.C. 331(ll)). Section 301(ll) of the FD&C 
Act 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 (ll)(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.

List of Subjects in 21 CFR Part 172

    Food additives, 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 21 CFR part 172 continues to read as 
follows:

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


0
2. Section 172.381 is added to subpart D to read as follows:


Sec.  172.381  Vitamin D2 bakers yeast.

    Vitamin D2 bakers yeast may be used safely in foods as a 
source of vitamin D2 and as a leavening agent in accordance 
with the following prescribed conditions:
    (a) Vitamin D2 bakers yeast is the substance produced by 
exposing bakers yeast (Saccharomyces cerevisiae) to ultraviolet light, 
resulting in the photochemical conversion of endogenous ergosterol in 
bakers yeast to vitamin D2 (also known as ergocalciferol or 
(9,10-seco(5Z,7E,22E)-5,7,10(19),22-ergostatetraen-3-ol)).
    (b) Vitamin D2 bakers yeast may be used alone as an 
active dry yeast concentrate or in combination with conventional bakers 
yeast.
    (c) The additive may be used in yeast-leavened baked goods and 
baking mixes and yeast-leavened baked snack foods at levels not to 
exceed 400 International Units of vitamin D2 per 100 grams 
in the finished food.
    (d) To assure safe use of the additive, the label or labeling of 
the food additive container shall bear, in addition to the other 
information required by the Federal Food, Drug, and Cosmetic Act, 
adequate directions for use to provide a final product that complies 
with the

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limitations prescribed in paragraph (c) of this section.
    (e) Labels of manufactured food products containing the additive 
shall bear, in the ingredient statement, the name of the additive, 
``vitamin D2 bakers yeast,'' in the proper order of 
decreasing predominance in the finished food.

    Dated: August 20, 2012.
Kirk B. Arvidson,
Acting Director, Office of Food Additive Safety, Center for Food Safety 
and Applied Nutrition.
[FR Doc. 2012-21353 Filed 8-28-12; 8:45 am]
BILLING CODE 4160-01-P


