[Federal Register Volume 65, Number 130 (Thursday, July 6, 2000)]
[Rules and Regulations]
[Pages 41581-41584]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-17018]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 73

[Docket No. 98C-0212]


Listing of Color Additives Exempt From Certification; 
Haematococcus Algae Meal

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

-----------------------------------------------------------------------

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-,-carotene-4,4'-dione), which exists

[[Page 41582]]

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).

[[Page 41583]]

IV. Stability of Astaxanthin in Haematococcus Algae Meal

    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 algae meal must be added to fish feed only in the form of 
a stabilized color additive mixture. Therefore, new 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 that 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

[[Page 41584]]

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.

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. Section 73.185 is added to subpart A to read as follows:


Sec. 73.185  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 certification 
requirements of section 721(c) of the act.

    Dated: June 27, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 00-17018 Filed 7-5-00; 8:45 am]
BILLING CODE 4160-01-F