[Federal Register Volume 65, Number 130 (Thursday, July 6, 2000)]
[Rules and Regulations]
[Pages 41584-41587]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-17019]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 73

[Docket No. 97C-0466]


Listing of Color Additives Exempt From Certification; Phaffia 
Yeast

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 phaffia yeast 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 Archer 
Daniels Midland Co.

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 November 19, 1997 
(62 FR 61823), FDA announced that a color additive petition (CAP 
8C0252) had been filed by Archer Daniels Midland Co., P.O. Box 1470, 
Decatur, IL 62525. The petition proposed to amend the color additive 
regulations to provide for the safe use of astaxanthin from Phaffia

[[Page 41585]]

rhodozyma as a color additive in salmonid fish feeds. During its review 
of the petition, the agency determined that the subject color additive 
is more accurately described as a dried preparation of the yeast P. 
rhodozyma that contains astaxanthin. Therefore, the agency is 
establishing phaffia yeast as the common or usual name of the color 
additive.

II. Identity, Technical Effect, and Specifications

    Phaffia yeast consists of the cells of the yeast P. rhodozyma that 
are produced by pure culture fermentation and subsequently killed by 
heat and dried. P. rhodozyma is the asexual form of the yeast species 
Xanthophyllomyces dendrorhous (Ref. 1). The major components of phaffia 
yeast are proteins, carbohydrates, and lipids produced by the yeast 
cells. The primary coloring substance in phaffia yeast is astaxanthin 
(3,3'-dihydroxy-,-carotene-4,4'-dione) (Ref. 2). One 
published (Ref. 3) and several unpublished studies included in the 
petition showed that phaffia yeast satisfactorily pigmented the flesh 
of the fish when it was fed to salmonid fish.
    In a final rule published in the Federal Register of April 13, 1995 
(60 FR 18736), the agency listed astaxanthin in Sec. 73.35 (21 CFR 
73.35) for use in the feed of salmonid fish. 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 for astaxanthin 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.
    Phaffia yeast 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 petitioner indicated that 
phaffia yeast 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 yeast components in phaffia yeast would 
interfere with the test methods. Furthermore, the petitioner specified 
the astaxanthin content of phaffia yeast to be not less than 0.4 
percent, whereas the corresponding specification for astaxanthin in 
Sec. 73.35(b) is not less than 96 percent. Therefore, the petitioner 
requested that a new regulation be established for phaffia yeast as a 
source of astaxanthin. The agency agrees with the petitioner that a new 
regulation is necessary to list phaffia yeast.
    During the fish feeding studies, phaffia yeast was mixed with fish 
feed in such quantities that the amount of astaxanthin in finished 
feeds did not exceed 80 milligrams per kilogram. The agency based its 
safety determination on this amount of astaxanthin and the petitioner 
requested that this level be specified in the listing regulation. 
However, the agency notes that astaxanthin in the feed of farm-raised 
salmonid fish may come not only from phaffia yeast, but also from the 
use of the color additive astaxanthin meeting the specifications of 
Sec. 73.35 and other color additives that are sources of astaxanthin 
the agency may list in the future. Therefore, newly added 
Sec. 73.355(c)(2) (21 CFR 73.355(c)(2)) requires that the quantity of 
astaxanthin in finished feed, from phaffia yeast when used alone or in 
combination with other astaxanthin color additive sources listed in 
part 73 (21 CFR part 73), shall not exceed 80 milligrams per kilogram 
(72 grams per ton) of finished feed.

III. Safety Evaluation

    In evaluating the safety of the use of phaffia yeast in fish feed, 
the agency considered: (1) The safety of astaxanthin in phaffia yeast 
to humans and fish, and (2) the safety of the other components in 
phaffia yeast 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 (Ref. 3). These 
fish obtain astaxanthin from the crustaceans that constitute a 
significant portion of their diet. A similar flesh color may be 
obtained in aquacultured salmonids by feeding them a diet supplemented 
with astaxanthin. In the final rule of April 13, 1995, 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 final rule of April 13, 1995, 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.
    In the final rule of April 13, 1995, the facts upon which the 
agency concluded 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 phaffia 
yeast is safe for use in the feed of salmonid fish. During the review 
of the present petition, the agency determined that astaxanthin from 
phaffia yeast 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 phaffia yeast will substitute for 
the fish feed uses of astaxanthin listed in Sec. 73.35, and that the 
petitioned use of phaffia yeast 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 phaffia yeast is safe for use in 
the feed of salmonid fish.

B. Safety of the Producing Organism

    The yeast P. rhodozyma naturally produces astaxanthin (Refs. 2 and 
3). The parent strain of P. rhodozyma used by the petitioner was 
originally obtained from a natural source. From this parent strain a 
new strain that produces more astaxanthin was derived using classical 
mutagenesis (nonrecombinant deoxyribonucleic acid (DNA)) techniques.
    Based on the data in the petition and other relevant material, the 
agency determined that: (1) consumers will not be directly exposed to 
phaffia yeast, but to astaxanthin remaining in fish that

[[Page 41586]]

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 phaffia yeast; (3) the results of 
studies during which rats and fish were fed phaffia yeast and bacterial 
mutagenicity tests did not reveal any adverse effects on these 
organisms, indicating the absence of toxic impurities in the yeast; (4) 
a literature search uncovered no reports of pathogenicity or 
toxicogenicity of P. rhodozyma; and (5) various yeasts are commonly 
used as feed in fish aquaculture with no deleterious effects on fish 
health. Based on this information, FDA concludes that the petitioned 
use of P. rhodozyma is safe (Ref. 4).

IV. Stability of Astaxanthin in Phaffia Yeast

    Based on the results of stability studies of phaffia yeast 
submitted by the petitioner, FDA concludes that to minimize chemical 
changes that would result in loss of color of astaxanthin, phaffia 
yeast must be added to fish feed only in the form of a stabilized color 
additive mixture. Therefore, newly added Sec. 73.355(a)(2) requires 
that phaffia yeast 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, phaffia yeast, 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 phaffia yeast, 
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 Federal Food, Drug, and Cosmetic 
Act (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 phaffia yeast requires the declaration of expiration dates 
because astaxanthin in phaffia yeast 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 
phaffia yeast is added, must identify the presence of the color 
additive under 21 CFR 501.4. New Sec. 73.355(d)(2) references 
Sec. 501.4 to ensure that the presence of phaffia yeast 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 phaffia 
yeast 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 phaffia 
yeast, to bear labeling even though such food is not in package form. 
Section 101.22 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 phaffia yeast because the ingredient 
label would notify the consumer that the fish is artificially colored. 
Without such ingredient labeling, food comprising salmonid fish with 
added phaffia yeast 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 phaffia yeast 
is required to declare the presence of the color additive or color 
additive mixture. New Sec. 73.355(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 phaffia yeast 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 phaffia yeast 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 phaffia yeast 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 8C0252 (November 
19, 1997, 62 FR 61823). 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,

[[Page 41587]]

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

    1. Golubev, W. I., ``Perfect State of Rhodomyces dendrorhous 
(Phaffia rhodozyma),'' Yeast, 11:101-110, 1995.
    2. Andrewes, A. G., H. J. Phaff, and M. P. Starr, ``Carotenoids of 
Phaffia rhodozyma, a Red-Pigmented Fermenting Yeast,'' Phytochemistry, 
15:1003-1007, 1976.
    3. Johnson, E. A., D. E. Conklin, and M. J. Lewis, ``The Yeast 
Phaffia rhodozyma as a Dietary Pigment Source for Salmonids and 
Crustaceans,'' Journal of the Fishers Research Board of Canada, 
34:2417-2421, 1977.
    4. Johnson, C. B., memorandum entitled ``Astaxanthin from Phaffia 
rhodozyma: 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. 73.355 is added to subpart A to read as follows:


Sec. 73.355  Phaffia yeast.

    (a) Identity. (1) The color additive phaffia yeast consists of the 
killed, dried cells of a nonpathogenic and nontoxicogenic strain of the 
yeast Phaffia rhodozyma.
    (2) Phaffia yeast 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 phaffia yeast 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. Phaffia yeast 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 0.4 percent.
    (c) Uses and restrictions. Phaffia yeast 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 phaffia 
yeast 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 phaffia yeast 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. 00-17019 Filed 7-5-00; 8:45 am]
BILLING CODE 4160-01-F