[Federal Register Volume 63, Number 59 (Friday, March 27, 1998)]
[Rules and Regulations]
[Pages 14814-14817]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-8127]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 73
[Docket No. 93C-0248]
Listing of Color Additives Exempt from Certification;
Canthaxanthin
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 canthaxanthin 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 BASF
Corp.
DATES: Effective April 28, 1998, except as to any provisions that may
be stayed by the filing of proper objections; written objections and
request for a hearing by April 27, 1998.
ADDRESSES: Submit written objections to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: James C. Wallwork, Center for Food
Safety and Applied Nutrition (HFS-215), Food and Drug Administration,
200 C St. SW., Washington, DC 20204-0001, 202-418-3078.
SUPPLEMENTARY INFORMATION:
I. Introduction
In a notice published in the Federal Register of August 12, 1993
(58 FR 42975), FDA announced that a color additive petition (CAP
3C0240) had been filed by BASF Corp., 100 Cherry Hill Rd., Parsippany,
NJ 07054. The petitioner requested that FDA amend the color additive
regulations to provide for the safe use of canthaxanthin as a color
additive in the feed of salmonid fish. The petition was filed under
section 721(d) of the Federal Food, Drug, and Cosmetic Act (the act)
(21 U.S.C. 379e(d)).
II. Safety Evaluation
Canthaxanthin (,-carotene-4,4'-dione) and
astaxanthin are two coloring substances found in wild salmonids (Refs.
1 and 2). They are responsible for imparting the pink or red coloring
to these fish. Astaxanthin, found in crustaceans that constitute a
significant portion of the diet of wild salmonids, is the primary
coloring substances found in wild salmonids (Ref. 2). Canthaxanthin
contributes less coloring to wild salmonids and is present at levels of
0.3 to 1.0 milligram per kilogram (mg/kg) (Ref. 1). Coloration of
aquacultured salmonids that is comparable to that in wild salmonids may
be achieved by feeding aquacultured salmonids a diet that is higher in
canthaxanthin than is present in the diet of wild fish.
Based on the data and information that is before the agency, FDA
has determined that the use of canthaxanthin in fish feed at a level of
80 mg/kg (72 grams (g)/ton) is safe. This level will result in 4 to 8
mg/kg of the color additive in the flesh of salmonids (Ref. 3).
As part of its safety evaluation, FDA estimated the cumulative
exposure to canthaxanthin. The cumulative exposure consists of exposure
from the proposed use in salmonids and the exposure from all currently
listed uses. FDA used data and information contained in the petition
concerning residues of canthaxanthin in salmonids to estimate the
exposure to canthaxanthin from the proposed use. The agency used these
data and information, in addition to data and information on the
currently regulated uses of canthaxanthin, to determine the cumulative
exposure to canthaxanthin.
FDA estimates that, for the petitioned use, a level of 8 mg of
canthaxanthin/kg salmonid flesh will result in an exposure of no
greater than 0.08 mg/person/day (mg/p/d) for an individual consuming
those fish at the 90th percentile (Ref. 4). To estimate, for this final
rule, the exposure to canthaxanthin from all currently regulated uses,
FDA used the poundages of canthaxanthin used in food taken from the
1982 and 1987 National Academy of Sciences' (NAS) surveys of additives
used in food (Ref. 5).
FDA previously estimated the exposure to canthaxanthin from
currently regulated uses, when, in 1985, FDA issued a regulation that
allowed the use of canthaxanthin in broiler chicken feed for coloring
skin (hereinafter referred to as ``the 1985 rule'') (50 FR 47532,
November 19, 1985). As part of its review of the BASF Corp. petition,
FDA evaluated the exposure to canthaxanthin, based on currently
regulated uses, and found that the calculation done for the 1985 rule
was erroneous in that it overestimated
[[Page 14815]]
exposure to the color additive. The preamble to the 1985 rule contained
a theoretical estimate of exposure to canthaxanthin based on use of the
color additive in all food. This worst case estimate for exposure to
canthaxanthin was determined to be 100 mg/p/d (Ref. 6). The estimated
exposure to canthaxanthin from its use in chicken feed (6 mg/p/d) was
then added to the 100 mg/p/d, resulting in a cumulative estimated
exposure of 106 mg/p/d.
FDA has now determined that the 100 mg/p/d estimate is unreasonably
exaggerated because for technologic and aesthetic reasons canthaxanthin
will not be used to color all foods. FDA has also determined that it is
incorrect to add the 6 mg/p/d estimate of exposure from its use in
chicken feed to the 100 mg/p/d worst case estimate because the worst
case estimate already included the intake of colored chicken.
Furthermore, FDA has determined that the 6 mg/p/d estimate of exposure
from colored chicken skin is unreasonably exaggerated because it would
require a daily intake of approximately 12,000 g (approximately 264
pounds) of chicken containing canthaxanthin at 50 part per billion
(ppb) to achieve this exposure to canthaxanthin. Consequently, FDA
recalculated the exposure to canthaxanthin from use in chicken feed,
and used the recalculated exposure level in order to determine the
exposure from all currently regulated uses of the color additive. FDA
then added the exposure from the proposed use of canthaxanthin in
salmonids to the exposure from the currently regulated uses to estimate
the cumulative exposure to canthaxanthin.
The use of canthaxanthin in feed results in a residual level of
canthaxanthin of 50 ppb in chicken meat, of 150 ppb in chicken fat, and
of 2 parts per million in chicken livers. Combining these data with
intakes of these foods gives an exposure to canthaxanthin from its use
in chicken feed of 0.007 mg/p/d (Ref. 7). FDA determined, based on the
1982 and 1987 NAS surveys, that the per capita disappearance of
canthaxanthin was 0.027 mg/p/d (1982 data) and 0.008 mg/p/d (1987
data). To provide a conservative, yet reasonable estimate of exposure
using these poundage data, FDA assumed that only 10 percent of the
population consumes the entire output of food colored with
canthaxanthin and chose the higher of the two per capita disappearances
(the 1982 data) to calculate a per capita exposure of 0.27 mg/p/d
(0.027 mg/p/d x 10 = 0.27 mg/p/d) from all pre-1985 uses of the color
additive. Adding the recalculated exposure from use in chicken feed
(0.007 mg/p/d) to the exposure from currently regulated uses based upon
the 1982 estimate of 0.27 mg/p/d results in a total exposure from
currently regulated uses of 0.28 mg/p/d. Therefore, the cumulative
exposure to canthaxanthin from its currently regulated uses plus the
petitioned use is 0.36 mg/p/d (0.28 mg/p/d current use + 0.08 mg/p/d
proposed use in salmonids).
Because of the numerous conservative assumptions used in
calculating exposure, the actual cumulative exposure from the current
and petitioned uses of canthaxanthin is likely to be substantially less
than the estimated cumulative exposure of 0.36 mg/p/d.
The acceptable daily intake (ADI) of canthaxanthin, as previously
determined by FDA, is 150 mg/p/d (50 FR 47532 at 47533). FDA's
estimates for the 90th percentile human exposure to canthaxanthin in
aquacultured fish flesh of 0.08 mg/p/d and the cumulative exposure for
canthaxanthin of 0.36 mg/p/d represent only small fractions of this
amount.
In 1996, the Joint Expert Committee on Food Additives (JECFA) of
the Food and Agriculture Organization and the World Health Organization
(WHO) determined an ADI of 0.03 mg/kg body weight (bw) (1.8 mg/p/d) for
canthaxanthin based on a no-observed-effect-level of 0.25 mg/kg bw/d in
humans and a safety factor of 10 (Ref. 8). JECFA's ADI was based on
consideration of recent reports of crystalline retinopathy in subjects
consuming large quantities of canthaxanthin as part of tanning pills
and animal studies conducted to study this retinal effect.
FDA has proceeded to make a determination on the petitioned use of
canthaxanthin even though it has yet to evaluate the studies that JECFA
considered in determining JECFA's 1996 ADI. FDA believes it is entirely
sound to do so because the exposure from the petitioned use of
canthaxanthin is well below both FDA's and JECFA's ADI (Ref. 9).
Nevertheless, the agency may determine, in response to a petition for
an additional use of canthaxanthin, that a reevaluation of the exposure
to this color additive is warranted, including consideration of the
studies that JECFA considered in arriving at its 1996 ADI.
The agency has reviewed the safety information for canthaxanthin
and finds that there is no basis for concern that harm will result to
consumers from the current and petitioned uses of canthaxanthin. Thus,
FDA concludes that there is a reasonable certainty of no harm from the
current and petitioned uses of canthaxanthin (Ref. 10).
FDA received one comment on the petition. This comment endorsed the
petitioned use of canthaxanthin.
III. Stability
FDA finds that canthaxanthin is relatively unstable. Pure
crystalline canthaxanthin must be stored in the absence of light, heat,
and oxygen to minimize chemical changes and decomposition that would
result in loss of color (Refs. 1 and 11). Thus, it is necessary to
produce a stabilized form of canthaxanthin for it to be marketed for
addition to salmonid feed for the purpose of coloring fish flesh.
Because of this concern, the petitioner manufactures canthaxanthin in a
beadlet form, which the manufacturer has shown provides increased
stability to the color additive mixture. Therefore, newly added
Sec. 73.75(c)(3)(i) (21 CFR 73.75(c)(3)(i)) requires that canthaxanthin
be added to fish feed only in the form of a stabilized color additive
mixture.
IV. 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, canthaxanthin, 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 canthaxanthin, 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 other representations made on the label and material with
respect to consequences which may result from the use of the color
additive. The use of canthaxanthin requires the declaration of
expiration dates because this relatively unstable color additive 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
[[Page 14816]]
additive mixture, the ingredient list on fish feed, to which
canthaxanthin is added, must identify the presence of the color
additive under Sec. 501.4 (21 CFR 501.4). New Sec. 73.75(d)(3)
references Sec. 501.4 to ensure that the presence of canthaxanthin 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
canthaxanthin 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
canthaxanthin, 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 canthaxanthin because the ingredient
label would notify the consumer that the fish is artificially colored.
Without such ingredient labeling, food comprising salmonid fish with
added canthaxanthin would be deemed to be misbranded under section
403(k) of the act which states that: ``A food shall be deemed to be
misbrandeded * * * 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 canthaxanthin
is required to declare the presence of the color additive or color
additive mixture. New Sec. 73.75(d)(4) references Secs. 101.22(b), (c),
and (k)(2), and 101.100(a)(2) to ensure that, at the retail level, the
presence of canthaxanthin 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.
V. Conclusions
FDA has evaluated the data in the petition and other relevant
material and concludes that canthaxanthin is safe and suitable for the
intended use, and therefore, that the regulations in Sec. 73.75 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
canthaxanthin is not necessary for the protection of the public health.
Because of the relative instability of crystalline canthaxanthin,
the agency believes that the use of this color additive should be in
the form of a stabilized color additive mixture for all regulated uses
of canthaxanthin. In addition, the agency believes that stability data
for canthaxanthin require that the labeling of this color additive for
all regulated uses include an expiration date. Therefore, the agency is
requiring, in new Sec. 73.75(c) and (d), that the use of canthaxanthin
in fish feed be in the form of a stabilized color additive mixture and
that the labeling include an expiration date. The currently listed uses
for canthaxanthin have no such requirements. Therefore, the agency
plans to publish a proposed rule to amend the current regulation in
Sec. 73.75 to require, for such uses, that canthaxanthin be in the form
of a stabilized color additive mixture and that the labeling include an
expiration date (Ref. 12).
VI. Inspection of Documents
In accordance with Sec. 71.15(a) (21 CFR 71.15(a)), 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 (address above) by
appointment with the information contact person listed above. As
provided in Sec. 71.15(b), the agency will delete from the documents
any materials that are not available for public disclosure before
making the documents available for inspection.
VII. Environmental Impact
The agency has carefully considered the potential environmental
effects of this action. FDA has concluded that the action will not have
a significant impact on the human environment, and that an
environmental impact statement is not required. The agency's finding of
no significant impact and the evidence supporting that finding,
contained in an environmental assessment, may be seen in the Dockets
Management Branch (address above) between 9 a.m. and 4 p.m., Monday
through Friday.
VIII. Objections
Any person who will be adversely affected by this regulation may at
any time on or before April 27, 1998, file with the Dockets Management
Branch (address above) written objections thereto. 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 shall be
submitted and shall 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.
IX. 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. Christophersen, A. G., P. Knuthsen, and L. H. Skibsted,
``Determination of Carotenoids in Salmonids,'' Zeitschrift fur
Lebensmittel-Untersuchung Forschung, 188:413-418, 1989.
2. Schiedt, K., F. J. Leuenberger, and M. Vecchi, ``Natural
Occurrence of Enantiomeric and Meso-Astaxanthin,'' Helvitica Chimica
Acta, 64:449-457, 1981.
3. Storebakken, T., P. Foss, K. Schiedt, E. Austreng, S. Liaaen-
Jensen, and U. Mainz, ``Carotenoids in Diets for Salmonids IV.
Pigmentation of Atlantic Salmon with Astaxanthin, Astaxanthin
Dipalmitate and Canthaxanthin,'' Aquaculture, 65: 279-292, 1987.
4. Memorandum from M. DiNovi, FDA, to J. Wallwork, FDA, May 17,
1996.
5. National Academy of Sciences, ``1987 Poundage and Technical
Effects Update of Substances Added to Food,'' p. 98, Washington, DC,
1989.
6. Memorandum from L. Borodinsky, FDA, to J. Taylor, FDA, April
28, 1989.
[[Page 14817]]
7. Memorandum from M. DiNovi, FDA, to J. Wallwork, FDA, August
29, 1996.
8. Olsen, P. ``Canthaxanthin,'' in Toxicological Evaluation of
Certain Food Additives and Contaminants in Food. WHO Food Additive
Series: 35, World Health Organization, Geneva, pp. 157-171, 1996.
9. Memorandum of April 17, 1997, FDA Meeting Regarding
Canthaxanthin: JECFA's 1996 ADI.
10. Memorandum from C. Johnson, FDA, to J. Wallwork, FDA,
September 10, 1996.
11. Bunnell, R. H., and B. Borenstein, ``Canthaxanthin, A
Potential New Food Color,'' Food Technology, 21: 13A-16A, 1967.
12. Memorandum of Telephone Conversation between J. Wallwork,
FDA, and S. Turujman, FDA, July 8, 1996.
List of Subjects in 21 CFR Part 73
Color additives, Cosmetics, Drugs, 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 73.75 is amended in paragraph (c)(1)(i) by removing the
period at the end and by adding ``; and'' in its place, by adding
paragraph (c)(3), and by revising paragraph (d) to read as follows:
Sec. 73.75 Canthaxanthin.
* * * * *
(c) * * *
(3) Canthaxanthin may be safely used in the feed of salmonid fish
in accordance with the following prescribed conditions:
(i) Canthaxanthin may be added to the fish feed only in the form of
a stabilized color additive mixture;
(ii) The color additive is used to enhance the pink to orange-red
color of the flesh of salmonid fish; and
(iii) The quantity of color additive in feed 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 mixture prepared therefrom intended solely or in part for
coloring purposes shall conform to the requirements of Sec. 70.25 of
this chapter.
(2) For purposes of coloring fish, the labeling of the color
additive and any premixes prepared therefrom shall bear expiration
dates (established through generally accepted stability testing
methods) for the sealed and open container, 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)(3) of this section.
(3) The presence of the color additive in finished fish feed
prepared according to paragraph (c)(3) of this section shall be
declared in accordance with Sec. 501.4 of this chapter.
(4) The presence of the color additive in salmonid fish that have
been fed feeds containing canthaxanthin shall be declared in accordance
with Secs. 101.22(b), (c), and (k)(2), and 101.100(a)(2) of this
chapter.
* * * * *
Dated: March 19, 1998.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 98-8127 Filed 3-26-98; 8:45 am]
BILLING CODE 4160-01-F