Listing of Color Additives Exempt from Certification; Canthaxanthin

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

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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

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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.

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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