Dunaliella bardawil alga

358 Pages·2011·15.4 MB·English

by  Nikken Sohonsha Corporation

ORIGINAL SUBMISSION
000001.059
GRAS Notification
Dunaliella Bardawil
Food Usage Conditions for General Recognition of Safety
Volume 1 of 2
Submitted for:
Nikken Sohonsha Corporation (Nikken)
1-32 Asahira, Fukuju-choyG ifu-Pref
50 1-6255 Hashima-city
JAPAN
Submitted bv:
Phoenix Regulatory Associates, Ltd.
21525 Ridgetop Circle, Suite 240
Sterling, Virginia 20 166
Phone: [phone] Fax: [phone]
Email: [email protected]
Internet: www .Dhoenixrisina.c orn
December 3 1,2008
000001.060

PHOENIX
__I_
REGULATORY ASSOCIATES, LTD.
Washington DC Headquarters
21525 Ridgetop Circle
Suite 240
Sterling, Virginia 20166
European Office: Dorset, England
December 3 1,2008
Robert Martin, Ph.D. VIA: Courier
Supervisory Consumer Safety Officer
Division of Biotechnology & GRAS Notice Review (HFS-255)
Center for Food Safety and Applied Nutrition
Food and Drug Administration
5 100 Paint Branch Parkway
College Park, MD 20740-3835
RE: GRAS Notification (GRN)f or Dunaliella bardawil alga
Dear Dr. Martin:
Phoenix Regulatory Associates, Ltd. (Phoenix) is submitting the enclosed GRAS notification on
behalf of Nikken Sohonsha Corporation (Nikken). In accordance with the Food and Drug
Administration’s (FDA) proposed policy [62 FR 18938-18964; April 17, 19971, Nikken is
voluntarily notifying the agency that it had a Panel of Experts review the data and information
available and concurs with that Panel’s conclusion based on scientific procedures that
Dunaliella bardawil alga dried powder substance is ‘generally recognized as safe’ (GRAS) for
the intended uses. In accordance with Section 201(s) of the Federal Food, Drug, and Cosmetic
Act, Nikken has determined that its food substance is exempt fiom the food additive premarket
provisions of the Act.
In addition, Nikken certifies that the intended uses of Dunaliella bardawil alga are similar to
those of other food algal substances and that its alga ingredient which contains p-carotene is not
intended for use as a color additive.
This cover letter contains the exemption claim as required by the proposed regulation and is
attached to the GRN that details Nikken’s basis for the GRAS determination. Appended to the
GRN are copics of the unpublished non-clinical studies that Nikken has conducted. Three
copies of the materials are enclosed as required by proposed 21 CFR 170.36(b).
In accordance with the proposed regulation, the following information is provided here in this
letter as well as in the GRN.
Proposed 21 CFR 170.36(c)(l)(i): The name and address of the notifier:
Nikken Sohonsha Corporation
1-32 Asahira, Fukuju-cho, Gifu-Pref
501-6255 Hashima-city
JAPAN
Phone [phone] Facsimile 703-406-9513 ~ O ( ) O p j
http://~w~v.phoenixrising.com email: [email protected]
PHOENIX
REGU1,ATOlIY ASSOCIKI’ES, I,lI>.
Robert Martin, Ph.D., Supervisory Consumer Safety Officer
Division of Biotechnology & GRAS Notice Review (HFS-255)
RE: Nikken Sohonsha Corporation, GRAS Notification (GRN) for Dunaliella bardawil alga
December 3 1,2008
Page Two
Proposed 21 CFR 170.3(c)(l)(ii): The common or usual name of the notified substance:
Dunaliella bardawil alga or Dunaliella bardawil dried powder
Proposed 21 CFR 170-3(c)(iii): The applicable conditions of use of the notified substance:
Dunaliella bardawil alga is intended to be added as an antioxidant and/or as a nutrient
supplement to the following selected food products: dairy products, cakes, mayonnaise
and salad oils, pudding and custards, crackers and cookies, wheat noodles, bread/rolls,
tofu, Kimchi and fermented soybean products.
Proposed 21 CFR 170.3(c)(l)(iv): The basis for the GRAS determination:
Scientific procedures
Proposed 21 CFR 170.3(c)(l)(v): Availability of information:
A summary of the data and information that supports this GRAS notification is
attached. If you have any questions or require additional information, please contact
Nikken’s US agent.
C. K. Gund, Ph.D., President
Phoenix Regulatory Associates, Ltd.
21525 Ridgetop Circle, Suite 240
Sterling, VA 20166
Phone: [phone]
Email: plioeiii?rO,phoenixrisinr.com.
President
Enclosures: Three (3) copies of GRAS Notification for Dunaliella bardawil alga

NIKKEN SOHONSHA CORPORATION
Privileged and Confidential December 31,2008
TABLE OF CONTENTS
Volume 1 of 2
- -
Item Pace Tab
Cover Letter ....................................................................................................................... 000003
Table of Contents ............................................................................................................... 000006
GRN Report - Dunaliella bardawil alga ........................................................................... 000008
Appendix A ........................................................................................................................ 000053
Appendix B ........................................................................................................................ 000056
Appendix C ........................................................................................................................ 000059
Attachments
Aruga, F., 1988. Mutagenecity Study of Dunaliella Bardawil Paste (revision test with
bacteria) Study Report, and Test Protocol, dated August 25, 1987, with one (1)
Amendment dated December 17, 1987, Hashima Laboratory, Nihon Bioresearch Inc,
submitted on February 5, 1988 (Japanese and English translation with certification
statement) ....................................................................................................................... 000074 1
Volume 2 of 2
Table of Contents. .............................................................................................................. 000157
Aruga, F., 1987. Acute Oral Toxicity Study on Dunaliella Bavdawil Spray Dried
Powder in Mice, dated December 8, 1987 and Protocol dated August 25, 1987,
with one (1) Amendment dated November 11, 1987 (Japanese and English
translation with certification statement) ......................................................................... 0001 59 2
Furuhashi T., 1989. Subacute Toxicity Study of Dunaliella Bavdawil Spray-Dried
Powder by 28-day Oral Administration in Rats, dated October 3 1, 1989, and
Protocol dated January 17, 1989, with four (4) amendments dated January 17,
1989, February 6, 1989, September 25, 1989, and October 17, 1989, respectively
(Japanese and English translation with certification statement) ..................................... 000236 3
Phoenix Regulatory Associates, Ltd.@ Page 1 of 1
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Dunaliella barda wil
Food Usage Conditions for General Recognition of Safety
for
Nikken Sohonsha Corporation
1-32 Asahira, Fukuju-cho
Hashima-city, Gifu-Pref. 501- 6255
Japan
Evaluation b)!:
Richard C. Kraska, Ph.D., DABT
Robert S. McQuate, Ph.D.
Robin C. Guy, M.S., DABT
Submitted by:
Phoenix Regulatory Associates, Ltd.
2 1525 Ridgetop Circle
Suite 240
Sterling, VA 20166
Phone: [phone] Fax: [phone]
E-mail: [email protected]
Internet: www.phoenixrising.com
December 29,2008
GRAS Assessment for Nikken Sohonsha Corporation
Dunaliella bardawil
Page 2 December 29. 2008
TABLE OF CONTENTS
.
1 GRAS EXEMPTION CLAIM. .................................................................................................. 4
A . Claim of Exemption from the Requirement for Premarket Approval Pursuant to
Proposed 21 CFR 170.36(~)(1.).. ....................................................................................... 4
B. Name and Address of Notifier. .......................................................................................... 4
C . Common Name and Identity of the Notified Substance. ......................................................... 4
D. Conditions of Intended Use in Food. .................................................................................. 5
E. Basis for the GRAS Determination. ................................................................................... 5
. . .
F. Availability of Information. ................................................................................................ 5
. ...............................................................................................................
I1 BACKGROUND.,, 6
A . Objective ...................................................................................................................... 6
B. Foreword. ..................................................................................................................... 6
C . FDA Regulatory Framework & Existing Regulations of Dunaliella bardawl& p-Carotene .............. 6
D. Additional Regulatory Background for Dunahella bardawil. ..................................................... 7
.
111 CHEMISTRY & MANUFACTURE OF DUNALIELLA BARDAW/. ................................................ 9
A . Chemistry of Dunaliella Dried Powder. ................................................................................ 9
B. Chemistry & Properties of p-Carotene. ................................................................................ 9
*-*e C . Product Description, Composition & Common or Usual Name. ................................................ 10
D. Manufacturing Procedure. ............................................................................................... 11
..
E. Stability Data. ............................................................................................................... 12
.
IV INTENDED DIETARY USES. ............................................................................................... 14
A . Intended Food Uses. ...................................................................................................... 14
B. Estimated Daily Intake. ................................................................................................... 14
. ..............................
C Estimate of Dietary Exposure to PCarotene from Natural & Added Sources 14
D. Other Information on Human Exposure to Dunahella bardawil: Use as a Food Ingredient
& Dietary Supplement. ................................................................................................... 16
.
V SAFETY DATA FOR DUNALlELLA BARDAWL & p.CAROTENE ............................................. 17
A . Dunaliella bardawil Safety Considerations., ........................................................................ 17
1. Clinical Studies on Nikken Dunaliella bardawil. ............................................................. 17
2 . Absorption, Distribution, Metabolism & Excretion (ADME) Studies .................................... 20
3 . Acute Toxicity Studies. ............................................................................................ 20
4 . Reproductive and Developmental Studies. ................................................................... 21
5 . Subacute & Subchronic Studies. ................................................................................ 23
a. 2-Week Study ................................................................................................... 23
b . 4-Week Study ................................................................................................... 23
c . Subchronic Studies (10-14 Week Dietary Exposure). ................................................ 24
. ...................................................................................................
d 6-Month Study 25
. .
6 . Mutagenicity & Genotoxicity.,. .................................................................................... 25
7. Other Clinical Studies on Dunaliella bardawil ................................................................. 26
0 0 0 0 0 4