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FDA Approval
of the Safe Use of Haematococcus Algae Meal as a Color Additive in the Feed of
Salmond fish to Enhance the Color of Their Flesh
Federal Register: July 6, 2000
(Volume 65, Number 130)
DEPARTMENT OF HEALTH AND HUMAN
SERVICES
Listing of Color Additives Exempt From Certification; Haematococcus Algae Meal
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration
(FDA) is amending the color additive
regulations to provide for the safe use of haematococcus algae meal as a
color additive in the feed of salmonid fish to
enhance the color of their flesh. This
action is in response to a petition filed by Cyanotech Corp..
DATES: This rule is effective August 8,
2000; except as to any provisions that may
be stayed by the filing of proper objections. Submit
written objections and requests for a hearing by August 7, 2000.
ADDRESSES: Submit written objections to the
Dockets Management Branch (HFA-305), Food
and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville,
MD 20852.
FOR FURTHER INFORMATION CONTACT: Aydin
Orstan, Center for Food Safety and Applied
Nutrition (HFS-215), Food and Drug Administration, 200 C St.
SW., Washington, DC 20204, 202-418-3076.
SUPPLEMENTARY INFORMATION:
I. Introduction
In a notice published in the
Federal Register of April 16, 1998 (63 FR
18920), FDA announced that a color additive petition (CAP 8C0256)
had been filed by Cyanotech Corp., 73-4460 Queen Kaahumanu Hwy., #102, Kailua-Kona,
HI 96740. The petition proposed to amend the color additive regulations
to provide for the safe use of haematococcus algae meal as a color additive in
salmonid fish feeds.
II. Identity, Technical Effect, and Specifications
Haematococcus algae meal
consists of the comminuted and dried cells of the alga Haematococcus
pluvialis (also known as H. lacustris). The major components of
haematococcus algae meal are proteins, carbohydrates, and lipids produced by
the alga cells. The primary coloring substance in haematococcus algae meal
is astaxanthin (3,3'-dihydroxy-<greek-b>,<greek-b>-carotene-4,4'-dione),
which exists primarily in esterified forms (Ref. 1). One published (Ref. 2)
and several unpublished studies included in the petition showed that
haematococcus algae meal satisfactorily pigmented the flesh of the fish when
it was fed to salmonid fish.
In the Federal Register of
April 13, 1995 (60 FR 18736), the agency published a final rule that listed
astaxanthin in Sec. 73.35 (21 CFR 73.35) for use in the feed of salmonid
fish (hereinafter referred to as the April 1995 final rule). In the preamble
to that rule, the agency stated that the
new regulation for astaxanthin did not specify the source of astaxanthin or
the manufacturing process, because the agency had made its safety
determination based on the chemical similarity of synthetic astaxanthin to
astaxanthin from natural sources. The agency concluded
that any source could be used to produce the color additive as long as the
astaxanthin meets the identity, specifications, and stability requirements
defined in Sec. 73.35, and it is manufactured in accordance with good
manufacturing practice. Furthermore, the agency stated in the astaxanthin
rule that the specifications were listed to convey the fact that FDA had
evaluated only a particular form of the color additive. The agency also
stated that it was concerned that deleterious materials not found in the
habitat of salmonids may be included in
fish feed from biomass products that contain only a small amount of
astaxanthin with the rest of the material being residues from the producing
organisms. Thus, the agency said that interested parties should submit
information in the form of a new color additive petition if they wish to
market a biomass product containing astaxanthin.
Haematococcus algae meal is a
biomass product that contains a relatively small amount of astaxanthin with
the rest of the material being proteins, carbohydrates, and lipids. In
addition, the agency determined that haematococcus algae meal would not meet
the specifications in Sec. 73.35(b) for solubility in chloroform, absorption
maximum wavelength, and residue on ignition, because some of the algal
components in haematococcus algae meal would interfere with the test
methods. Furthermore, the petitioner specified the astaxanthin content of
haematococcus algae meal to be not less than 1.5 percent, whereas the
corresponding specification for astaxanthin in Sec. 73.35(b) is not less
than 96 percent. Therefore, the agency concludes that a new regulation is
necessary to list haematococcus algae meal.
In the April 1995 final rule,
the agency concluded that 80 milligrams per kilogram (mg/kg) of astaxanthin
in fish feed would result in adequate pigmentation of the flesh of salmonids.
Therefore, in Sec. 73.35(c)(2) the agency limited the astaxanthin content of
finished feed to not more than 80 mg/kg. However, the agency now notes that
astaxanthin in the feed of farm-raised salmonid fish may come not only from
the color additive astaxanthin meeting the specifications of Sec. 73.35, but
also from the color additive haematococcus algae meal
and other color additives that are sources of
astaxanthin the agency may list in the future. Therefore, new Sec.
73.185(c)(2) requires that the quantity of astaxanthin in finished feed,
from haematococcus algae meal when used alone or in combination with other
astaxanthin color additive sources listed in part 73 (21 CFR part 73), shall
not exceed 80 mg/kg (72 grams per ton) of finished feed.
III. Safety Evaluation
In evaluating the safety of the
use of haematococcus algae meal in fish feed, the
agency considered: (1) The safety of astaxanthin in haematococcus algae meal
to humans and fish, and (2) the safety of the
other components in haematococcus algae
meal to humans and fish.
A. Safety of Astaxanthin
Astaxanthin is the principal pigment that imparts
the pink or red coloring characteristic of the flesh of wild salmonids. These
fish obtain astaxanthin from the crustaceans that constitute a significant
portion of their diet (Ref. 3). A similar flesh color may be obtained in
aquacultured salmonids by feeding them a diet supplemented with astaxanthin.
In the April 1995 final rule, the agency concluded that astaxanthin was safe
for use in the feed of salmonid fish. This
conclusion was based on the following facts: (1)
The petitioned use of astaxanthin would result in deposition of a very small
amount of astaxanthin in salmonid flesh; (2) astaxanthin that was the subject
of the April 1995 final rule, differed from astaxanthin present in the
flesh of wild salmon only in its optical isomeric
distribution; (3) human exposure to astaxanthin from consumption of
aquacultured salmon fed synthetic astaxanthin is comparable to the exposure to
astaxanthin from wild salmon. In addition, the results of the toxicity studies
submitted by the petitioner supported the
conclusion that there was reasonable certainty of no harm from the petitioned
use of astaxanthin.
The facts upon which the agency
concluded, in the April 1995 final rule, that astaxanthin was safe for use in
the feed of salmonid fish, are similar to the facts upon which the agency is
basing its conclusion that astaxanthin from the petitioned use of
haematococcus algae meal is
safe for use in the feed of salmonid fish. During
the review of the present petition, the agency determined that in both
crustaceans and H. pluvialis, astaxanthin is mainly in esterified forms that
are converted to free astaxanthin during digestion and deposited as such in
fish flesh (Ref. 4). The agency also determined that free astaxanthin from H.
pluvialis differed from astaxanthin present in the flesh of wild salmon only
in its optical isomeric distribution and that the petitioned use of
astaxanthin would result in deposition of a very small amount of astaxanthin
in salmonid flesh. Furthermore, the agency determined that the astaxanthin
from haematococcus algae meal will substitute for the fish feed uses of
astaxanthin listed in Sec. 73.35, and that the petitioned use of haematococcus
algae meal will not increase the estimated daily intake of astaxanthin in
humans, which is comparable to the exposure to astaxanthin from wild salmon.
Therefore, the agency concludes that astaxanthin from the petitioned use of
haematococcus algae meal is safe for use in the feed of salmonid fish.
B. Safety of the Producing Organism
Based on the data in the petition and other
relevant material, the agency determined
that: (1) Consumers will not be directly exposed to haematococcus
algae meal, but to astaxanthin remaining in fish that have
consumed the yeast in their diet; (2) there is no evidence that any
constituents other than astaxanthin will accumulate in fish maintained
on diets supplemented with haematococcus algae meal; (3) the results
of studies during which rats and salmon were fed haematococcus algae
meal and bacterial mutagenicity tests did not reveal any adverse effects,
indicating the absence of toxic impurities in the algae; (4) a literature
search uncovered no reports of pathogenicity or toxicogenicity
of H. pluvialis; and (5) algae are commonly used as feed components
in fish aquaculture with no deleterious effects on fish health.
Based on this information, FDA concludes that the petitioned use
of haematococcus algae meal is safe (Ref. 5).
IV. Stability of Astaxanthin in Phaffia Yeast
Based on the results of
stability studies of haematococcus algae meal submitted by the petitioner, FDA
concludes that to minimize chemical changes
that would result in loss of color of astaxanthin, haematococcus meal must be
added to fish feed only in the form of a stabilized color additive
mixture. Therefore, newly added Sec. 73.185(a)(2) requires that
haematococcus algae meal be added to fish feed only as a component of a
stabilized color additive mixture.
V. Labeling Requirements
All color additives, in
accordance with Sec. 70.25 (21 CFR 70.25), require
sufficient information to assure their safe use and to allow a determination
of compliance with any limitations imposed by the agency in
other applicable regulations. Therefore, the labeling of the color additive,
haematococcus algae meal, and any mixture prepared therefrom, is subject
to the requirements of Sec. 70.25.
According to Sec. 70.25(a)(4),
an expiration date for a color additive
must be stated on its label if stability data require it. FDA finds
that because of the instability of astaxanthin in haematococcus algae meal,
an expiration date must be stated on the label of
sealed and open containers, in accordance
with Sec. 70.25(a)(4). FDA also finds that declaration
of the expiration date constitutes a material fact that must
be disclosed on the label of the color additive mixture under sections
201(n) and 403(a)(1) of the act (21 U.S.C. 321(n) and 343(a)(1)) because
failure to do so would constitute a failure
to reveal facts material in light of the representations
made on the label and material with respect to consequences
which may result from the use of the color additive. The use
of haematococcus algae meal requires the declaration of expiration dates
because astaxanthin in haematococcus algae meal
can decompose to products that would not be
coloring agents and thus would not affect the color of salmonid
flesh.
In addition to the requirements
for labeling the color additive or color
additive mixture, the ingredient list on fish feed, to which haematococcus
algae meal is added, must identify the
presence of the color additive under Sec.
501.4 (21 CFR 501.4). New Sec. 73.185(d)(2) references Sec.
501.4 to ensure that the presence of haematococcus algae meal as a color
additive in the fish feed will be declared on the
ingredient label.
Finally, the presence of the
color additive must be declared on the label
of any food, including salmonid fish, containing added haematococcus algae
meal and food containing such salmonid fish as an ingredient. Section 101.22(b)
(21 CFR 101.22(b)) requires a food that bears or contains artificial
coloring, such as salmon artificially colored with haematococcus algae meal,
to bear labeling even though such food is not in package form. Section
101.22(c) requires that label statements of artificial coloring be ``likely
to be read by the ordinary person under customary conditions of
purchase and use of such food.''
Furthermore, Sec. 101.22(k)(2)
requires, in the statement of ingredients
for a food to which any coloring has been added, and for which
the coloring is not subject to certification, a declaration that makes
it clear that a color additive has been used in the food. In addition,
the presence of a color additive must be declared on any bulk container
of food containing a color additive that is held at a retail establishment
under the provisions in Sec. 101.100(a)(2) (21 CFR
101.100(a)(2)). The ingredient label would prevent
economic fraud in salmonid fish containing
added haematococcus algae meal because the ingredient label
would notify the consumer that the fish is artificially colored. Without
such ingredient labeling, food comprising salmonid fish with added
haematococcus algae meal would be deemed to be misbranded under section
403(k) of the act, which states that: A food shall
be deemed to be misbranded ``If it bears or
contains any artificial flavoring, artificial
coloring, or chemical preservative, unless it bears labeling stating
that fact * * *.''
Therefore, in accordance with
Secs. 101.22(b), (c), and (k)(2), and 101.100(a)(2),
labeling on any salmonid fish containing haematococcus algae meal
is required to declare the presence of the color
additive or color additive mixture. New
Sec. 73.185(d)(3) references Secs. 101.22(b), (c),
and (k)(2), and 101.100(a)(2) to ensure that, at the retail level, the
presence of haematococcus algae meal as a color additive in the fish will be
declared, and that the labeling of the bulk fish
container, including a list of ingredients,
will be displayed on the container or on a counter card
with similar information. In the future, the agency also intends to
propose to amend Sec. 73.35(d)(3) to include references to Sec.
101.22(b) and (c).
VI. Conclusion
Based on the data in the
petition and other relevant material, FDA concludes
that the petitioned use of haematococcus algae meal as a color additive
in fish feed to color the flesh of salmonid fish
is safe, the additive will achieve its
intended technical effect, and therefore, part 73 should
be amended as set forth below. In addition, based upon the factors
listed in 21 CFR 71.20(b), the agency concludes that certification
of haematococcus algae meal is not necessary for the protection of the
public health.
VII. Inspection of Documents
In accordance with Sec. 71.15
(21 CFR 71.15), 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 listed above. As provided in Sec. 71.15, the agency will delete
from the documents any materials that are not available for public
disclosure before making the documents available for inspection.
VIII. Environmental Impact
The agency has previously
considered the environmental effects of this
rule as announced in the notice of filing for CAP 8C0256. 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.
IX. Paperwork Reduction Act of 1995
This final rule contains no
collections of information. Therefore, clearance
by the Office of Management and Budget under the Paperwork Reduction
Act of 1995 is not required.
X. Objections
Any person who will be
adversely affected by this regulation may at any
time file with the Dockets Management Branch (address above) written
objections by August 7, 2000. 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 Dockets Management Branch between 9 a.m. and 4 p.m., Monday through
Friday. FDA will publish notice of the objections that the agency
has received or lack thereof in the Federal Register.
XI. References
The following references have been placed on
display in the Dockets Management Branch
(address above) and may be seen by interested persons between
9 a.m. and 4 p.m., Monday through Friday.
1. Renstrom, B., G. Borch, O.
M. Skulberg, and S. Liaaen-Jensen, ``Optical
Purity of (3S,3'S)-Astaxanthin from Haematococcus pluvialis,''
Phytochemistry, 20:2561-2564, 1981.
2. Sommer, T. R., W. T.
Potts, and N. M. Morrissy, ``Utilization of Microalgal
Astaxanthin by Rainbow Trout (Oncorhynchus mykiss),'' Aquaculture,
94:79-88, 1991.
3. Kitahara, T., ``Carotenoids
in the Pacific Salmon During the Marine
Period,'' Comprehensive Biochemistry and Physiology, 78B:859- 862,
1984.
4. Mori, T., K. Makabe, K.
Yamaguchi, S. Konosu, and S. Arai, ``Comparison
Between Krill Astaxanthin Diester and Synthesized Free Astaxanthin
Supplemented to Diets in Their Absorption and Deposition by Juvenile
Coho Salmon (Oncorhynchus kisutch),'' Comprehensive
Biochemistry and Physiology, 93B:255-258, 1989.
5. Johnson, C. B., Memorandum
entitled ``Haematococcus pluvialis Algae
Meal for Use in Feed for Salmonids: Final Toxicology Review'' from
the Division of Health Effects Evaluation (HFS-225) to the Division
of Petition Control (HFS-215), Center for Food Safety and Applied
Nutrition, FDA, August 12, 1999.
List of Subjects in 21 CFR Part 73
Color additives, Cosmetics,
Drugs, Foods, Medical devices.
Therefore, under the Federal
Food, Drug, and Cosmetic Act and under authority
delegated to the Commissioner of Food and Drugs, 21 CFR part 73
is amended as follows:
PART 73--LISTING OF COLOR ADDITIVES EXEMPT FROM
CERTIFICATION
1. The authority citation for
21 CFR part 73 continues to read as follows:
Authority: 21 U.S.C. 321, 341, 342, 343, 348, 351, 352, 355, 361,
362, 371, 379e.
2. New Sec. 73.185 is added to
subpart A to read as follows:
Sec.
73.355 Haematococcus algae meal.
(a) Identity.
(1) The color additive haematococcus algae meal consists of the comminuted and dried cells of the alga Haematococcus pluvialis.
(2) Haematococcus
algae meal may be added to the fish feed only as a component of
a stabilized color additive mixture. Color additive mixtures for fish
feed use made with haematococcus algae meal may contain only those diluents
that are suitable and are listed in this subpart
as safe for use in color
additive mixtures for coloring foods.
(b) Specifications. Haematococcus algae
meal shall conform to the following specifications
and shall be free from impurities other than those named to
the extent that such impurities may be avoided by good manufacturing practice:
Physical state, solid.
Lead, not more than 5 parts per million.
Arsenic, not more than 2 parts per million.
Mercury, not more than 1 part per million.
Heavy metals (as Pb), not more than 10 parts per million.
Astaxanthin, not less than 1.5 percent.
(c) Uses and restrictions. Haematococcus
algae meal may be safely used in the feed
of salmonid fish in accordance with the following prescribed conditions:
(1) The color additive is used
to enhance the pink to orange-red color of the flesh of salmonid fish.
(2) The quantity of astaxanthin
in finished feed, from Haematococcus algae meal when used
alone or in combination with other astaxanthin color additive sources listed in this part 73, shall not exceed 80 milligrams per kilogram (72 grams per ton) of finished feed.
(d) Labeling requirements. (1)
The labeling of the color additive and any
premixes prepared therefrom shall bear expiration dates for the sealed
and open container (established through generally accepted stability
testing methods), other information required by Sec. 70.25 of this
chapter, and adequate directions to prepare a final product complying
with the limitations prescribed in paragraph (c) of this section.
(2) The presence of the color
additive in finished fish feed prepared
according to paragraph (c)
of this section shall be declared in accordance with Sec. 501.4 of this chapter.
(3) The presence of the color
additive in salmonid fish that have been
fed feeds containing haematococcus
algae meal shall be declared in accordance
with Secs. 101.22(b), (c), and (k)(2) and
101.100(a)(2) of this chapter.
(e) Exemption from
certification. Certification of this color additive
is not necessary for the protection of the public
health, and therefore batches thereof are
exempt from the certification6 requirements
of section 721(c) of the act.
Dated: June 27, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 00-17019 Filed 7-5-00; 8:45 am]
BILLING CODE 4160-01-F
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