[Federal Register Volume 61, Number 43 (Monday, March 4, 1996)]
[Proposed Rules]
[Pages 8372-8417]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-4584]
[[Page 8371]]
_______________________________________________________________________
Part III
Department of Health and Human Services
_______________________________________________________________________
Food and Drug Administration
_______________________________________________________________________
21 CFR Part 70, et al.
Permanent Listing of Color Additive Lakes; Proposed Rule
Federal Register / Vol. 61, No. 43 / Monday, March 4, 1996 / Proposed
Rules
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 70, 73, 74, 80, 81, 82, 101, 178, 201, and 701
[Docket Nos. 79N-0043 and 92N-0334]
Permanent Listing of Color Additive Lakes
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to list
certain color additive lakes permanently as suitable and safe for use
in food, drugs, and cosmetics. The agency is proposing to permit the
use of more than one straight color in the preparation of a lake, to
modify the nomenclature for lakes, and to simplify the batch
certification procedure for lakes. As part of these actions, the agency
is proposing to amend its regulations to require the preparation of
lakes from certified batches of straight color; to provide simplified
nomenclature for declaring color additives, including lakes, on
cosmetic products; to require declaration of FD&C Yellow No. 5 and FD&C
Yellow No. 6 on all foods and some drug products containing lakes of
these straight colors; and to terminate the listing of certain straight
colors as components of lakes for drug and cosmetic use and the listing
of calcium salts as components of lakes for food use.
This proposed rule is intended to complete the agency's disposition
of the provisional list of color additives that was established under
the transitional provisions of the Color Additive Amendments of 1960
(the 1960 amendments) and to establish regulations prescribing
conditions under which lakes may be prepared, labeled, and safely used
in food, drugs, and cosmetics.
DATES: Written comments by June 3, 1996, except that comments regarding
information collection should be submitted by April 3, 1996, but not
later than May 3, 1996.
ADDRESSES: Written comments to the Dockets Management Branch (HFA-305),
Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, Rockville,
MD 20857. Comments regarding information collection to the Office of
Information and Regulatory Affairs, OMB, New Executive Office Building,
rm. 10235, Washington, DC 20503, ATTN: Desk Officer for FDA. Process
descriptions, identity information for anions in precipitants, and
ingredient specifications for substrata (including rosin), and rosin
samples to the Colors Technology Branch (HFS-126), Food and Drug
Administration, 200 C St. SW., Washington, DC 20204.
FOR FURTHER INFORMATION CONTACT:
Regarding proposed certification procedures, including proposed
paperwork requirements, and for proposed product ingredient
declarations:
Julie N. Barrows, Center for Food Safety and Applied Nutrition (HFS-
126), Food and Drug Administration, 200 C St. SW., Washington, DC
20204, 202-205-4662.
Regarding other issues:
Arthur L. Lipman, Center for Food Safety and Applied Nutrition (HFS-
217), Food and Drug Administration, 200 C St. SW., Washington, DC
20204, 202-418-3073.
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Identity, Manufacture, and Properties of Lakes
II. Regulatory History and Current Listings of Lakes
A. Regulatory History of Lakes
B. Current Listings of Lakes
C. The 1965 Proposal for Permanent Listing of Lakes and the 1979
Notice of Intent
III. Development of Proposed Actions for Lakes
A. Terminology of Lakes
B. Nomenclature of Lakes
C. Issues Relating to Definition of Lakes and Termination of
Certain Provisional Listings
IV. Safety Review and Proposed Actions for Lakes for Use in Foods
A. Review of Components of Lakes for Use in Foods
B. Specifications for Lakes for Use in Foods
C. Certification Requirement
D. Provisions of Proposed Sec. 74.50 Lakes for Use in Foods
V. Safety Review and Proposed Actions for Lakes for Use in Drugs and
Cosmetics
A. Review of Components of Lakes for Use in Drugs and Cosmetics
B. Specifications for Lakes for Use in Drugs and Cosmetics
C. Certification Requirement
D. Provisions of Proposed Regulations
VI. Other Proposed Actions
A. Removal of Provisional Listings
B. Certification Procedure for Lakes
C. Amendments to Other Regulations
VII. Summary of Information Requested
A. In Situ Manufacturing Processes
B. Identity and Specifications for Rosin
C. Anions in Precipitants
VIII. Effective Date
IX. Inspection of Documents
X. Environmental Impact
XI. Paperwork Reduction Act
XII. Comments
XIII. References
I. Identity, Manufacture, and Properties of Lakes
Color additives may be added to food, drugs, cosmetics, and certain
medical devices for the purpose of imparting color. The three
categories of color additives are: (1) ``Straight colors'' (color
additives that have not been mixed or chemically reacted with any other
substance); (2) lakes (color additives formed by chemically reacting a
straight color with water-insoluble substances); and (3) mixtures
(color additives formed by mixing a color additive with one or more
other color additives or noncolored substances, without chemical
reaction.)
A lake is a water-insoluble pigment composed of a water-soluble
straight color strongly adsorbed onto an insoluble substratum through
use of a precipitant. The regulations in part 82 (21 CFR part 82),
where lakes are provisionally listed, use the term ``basic radical'' to
denote a precipitant. As more fully described in section III.A.6. of
this document, the agency is proposing to replace the term ``basic
radical'' with the more scientifically accurate term ``precipitant.''
The proposed terminology will be used throughout the rest of this
document.
The first step in manufacturing a lake is the preparation of an
aqueous slurry of the substratum (e.g., alumina). This aqueous slurry
is mixed with an aqueous solution of a straight color to produce a
partially precipitated (or laked) product. The laking process is
completed by the addition of a precipitant (e.g., aluminum chloride),
which results in the production of the salt (e.g., aluminum salt) of
the straight color and the adsorption of the salt onto the substratum.
The resulting lake is washed, dried, and finely ground before
marketing.
The literature reports several variations of the basic laking
process (Refs. 1 through 5). Some substrata are synthesized in situ;
i.e., the components used to prepare the substratum, rather than the
preformed substratum, are added during the laking procedure. For
example, alumina slurries may be prepared by precipitation of hydrated
alumina from an aluminum sulfate solution with a sodium carbonate or
sodium hydroxide solution. These slurries are used directly in the
synthesis of lakes, without isolation of the precipitated substratum.
Some lakes are themselves prepared in situ. In this process, the
chemical precursors for the straight color are mixed directly with the
substratum and the precipitant during the laking procedure. The lake is
produced as the
[[Page 8373]]
straight color is synthesized, without isolation of the straight color
as a discrete batch.
The chemical association between the components of a lake may
involve various types of interactions, including ionic bonds, hydrogen
bonds, and van der Waals forces (Refs. 4 through 9). Lakes generally
contain 10 to 40 percent by weight of the straight color. They also
contain approximately 1 to 4 percent of the weight of the lake as the
cationic precipitant. The remaining 56 to 89 percent, by weight, of
lakes consists primarily of substrata. The color content of a lake
depends on the desired color intensity and shade of the lake.
Lakes offer many technical advantages over water-soluble straight
colors. The chemical bonding of the color with substrata generally
promotes light and heat stability. Furthermore, because lakes are not
water-soluble, the use of lakes in aqueous foods reduces color
migration.
The agency's current regulations for lakes in part 82 were issued
under section 203 of the Color Additive Amendments of 1960 (Pub. L. 86-
618), which provided for the temporary, provisional listing of
commercially established colors. The regulations provide that before a
lake may be used in a food, drug, or cosmetic product, each batch of
the lake must be certified by FDA. When requesting certification of a
batch of a lake, the requester submits a sample from the batch to the
agency for analysis. If the agency finds that the concentrations of
impurities in the sample are within the levels specified, and the batch
otherwise appears to comply with the applicable regulations, the agency
certifies the batch by issuing the requester a certificate showing the
certification lot number assigned to that batch of lake.
Lakes represent approximately 25 percent of the total poundage of
color additives certified by FDA. Approximately 80 percent of the lakes
certified are FD&C (food, drugs, and cosmetics) lakes and the remaining
20 percent are D&C (drugs and cosmetics) lakes. (See section II.A. of
this document for an explanation of the terms ``FD&C'' and ``D&C''.)
II. Regulatory History and Current Listings of Lakes
A. Regulatory History of Lakes
Section 7 of the Food and Drugs Act of 1906 (Pub. L. 59-384)
prohibited the use of poisonous or deleterious colors in confectionery
and the coloring or staining of food to conceal damage or inferiority.
In 1907, the agency, then part of the Department of Agriculture, issued
Food Inspection Decision 76 (Ref. 10), which contains a list of seven
straight colors approved for use in food. Between 1907 and 1939, the
agency expanded the list of straight colors approved for use in food
from 7 to 15. These colors were known as ``coal tar colors'' because
they were synthesized mainly from substances obtained from coal tar.
However, prior to 1939, the agency's list of acceptable colors did not
include lakes of coal tar colors because such lakes were not used in
food. Also, prior to 1938, the government program for batch analysis
and certification of colors was voluntary.
The Federal Food, Drug, and Cosmetic Act of 1938 (21 U.S.C. 301 et
seq. (the act)) (Pub. L. 75-717) required FDA to list coal tar colors
``harmless and suitable'' for use in foods, drugs, and cosmetics, and
to certify all batches of listed colors, including lakes. The agency
issued regulations under the act listing lakes for food use, as well as
for drug and cosmetic use, and establishing conditions for
certification of batches of lakes (4 FR 1922, May 9, 1939; 4 FR 3931,
September 16, 1939; and 5 FR 1138, March 23, 1940). The agency issued
the first certificate for a lake under the act on May 11, 1939 (Ref.
11).
The initial listing of lakes for food use under the act restricted
their use to coloring shell eggs (egg dyeing) (5 FR 1138). In 1959, at
the request of industry, the agency expanded the uses of lakes prepared
from FD&C straight colors to encompass general use in foods (24 FR
3818, May 13, 1959; and 24 FR 5302, June 30, 1959).
The 1960 amendments amended the act by defining the term ``color
additive'' (section 201(t) (21 U.S.C. 321(t))) for the first time and
restricting the use of color additives in or on food, drugs, cosmetics,
or the human body to those listed in FDA regulations. (The Medical
Device Amendments of 1976 (Pub. L. 94-295) extended these restrictions
to the use of color additives in certain medical devices.) As amended,
the act provides that a food (section 402(c) (21 U.S.C. 342(c))), drug
or device (section 501(a)(4) (21 U.S.C. 351(a)(4))), or cosmetic, other
than a coal tar hair dye (section 601(e) (21 U.S.C. 361(e))), is
adulterated if it is, bears, or contains an unsafe color additive.
Section 721 (formerly section 706) of the amended act (21 U.S.C. 379e)
provides for the listing of safe and suitable color additives for use
in foods, drugs, cosmetics, and medical devices; it prohibits the
listing of a color additive for a proposed use unless data establish
that such use will be safe. Section 721 of the act also continues the
requirement for certification of batches of color additives, with or
without diluents, to determine whether each batch conforms to the
purity and identity specifications in the applicable listing
regulation. However, the amendments allow FDA to exempt color additives
from batch certification if certification is unnecessary to protect the
public health.
Section 203 of the 1960 amendments also provided for the
provisional listing of color additives that were commercially
established when the 1960 amendments were enacted, pending completion
of scientific investigations necessary to determine their safety under
the new standard established by the 1960 amendments. The purpose of
section 203 was to allow the use of such color additives on an interim
basis, to the extent consistent with the public health. Section 203
directed the agency to recognize as provisionally listed the following
color additives: (1) Any color additive which, on the day preceding the
enactment date, was listed and certifiable for any use or uses and for
which a batch or batches had been certified for such use or uses prior
to the enactment date; (2) any color additive which was commercially
used or sold prior to the enactment date for any use or uses on any
food, drug, or cosmetic, but was not required to be listed under the
act; (3) synthetic beta carotene. The provisional listing was to apply
only to the use or uses to which the certification applied, or for
which the color additive had been commercially used or sold.
Under the authority of the 1960 amendments, in the Federal Register
of October 12, 1960 (25 FR 9759), the agency provisionally listed those
color additives, including lakes, covered by section 203. This listing,
originally codified as 21 CFR 8.501 and later recodified as Sec. 81.1
(21 CFR 81.1) (42 FR 15665, March 22, 1977) included many of the coal
tar colors (including lakes) that had been previously listed.
In the Federal Register of December 27, 1963 (28 FR 14311), the
agency determined that batch certification was unnecessary to ensure
the safety of most color additives derived from plant, animal, or
mineral sources, and designated these color additives as exempt from
certification. However, the agency determined that batch certification
was necessary to ensure the safety of most color additives, including
lakes, derived principally from coal and petroleum sources, and
designated those colors as subject to certification. Currently, the
color additives exempt from batch certification and the permanently
listed color additives
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subject to batch certification are listed in parts 73 and 74 (21 CFR
parts 73 and 74), respectively.
Since the establishment of the provisional list in 1960, the agency
has gradually removed color additives from the list either by permanent
listing or by termination of listing due to lack of interest by
industry or due to safety concerns prompted by the agency's reviews. At
this time, only lakes remain provisionally listed in parts 81 and 82.
After the enactment of the act in 1938, FDA established the
designation ``FD&C'' to identify color additives listed for use in
foods, drugs, and cosmetics; the designation ``D&C'' to identify color
additives listed for general use in drugs and cosmetics, but not foods;
and the designation ``Ext. D&C'' to identify color additives listed for
use only in externally applied drugs and cosmetics (4 FR 1922 at 1923).
These designations are still part of the names of certified color
additives. However, the uses of some straight colors (and consequently
also of their lakes) were restricted when they were permanently listed,
based on the safety reviews conducted by the agency under the 1960
amendments. Consequently, the designations ``FD&C'' or ``D&C'' in the
name of a certified color additive can no longer be relied upon to
accurately describe the approved uses of the color additive.
B. Current Listings of Lakes
1. Provisional Listing and General Provisions for Lakes
Section 81.1 identifies the provisionally listed color additives.
The only color additives remaining on the provisional list are lakes
(Sec. 81.1(a), (b), and (c)).
Part 82, subpart A, prescribes the general provisions applicable to
provisionally listed color additives. Section 82.3 contains definitions
of terms such as ``alumina'' and ``blanc fixe.'' Section 82.5
prescribes general specifications, including specifications for levels
of lead, arsenic, and heavy metals other than lead and arsenic, that
are applicable to lakes listed in the other subparts of part 82. It
also provides a specification for the level of soluble barium
applicable to lakes listed in subpart C or D of part 82 that contain a
barium salt.
2. Provisional Listing of Lakes for Use in Foods, Drugs, and Cosmetics
Part 82, subpart B, identifies the lakes that are provisionally
listed for use in foods, drugs, and cosmetics. Section 82.50 prescribes
the certification requirements for these lakes.
Section 82.51 specifies that lakes for use in foods, drugs, and
cosmetics are made by extending, on a substratum of alumina, a salt of
one of the following certified water-soluble straight colors with the
cation precipitant aluminum or calcium: FD&C Blue No. 1 (Sec. 82.101);
FD&C Blue No. 2 (Sec. 82.102); FD&C Green No. 3 (Sec. 82.203); FD&C
Yellow No. 5 (Sec. 82.705); and FD&C Yellow No. 6 (Sec. 82.706). Only
previously certified batches of the straight color may be used. Section
82.51 also provides specifications for soluble chlorides and sulfates
and for inorganic matter insoluble in hydrochloric acid (HCl) and
prescribes rules for naming the lakes that are listed for use in foods,
drugs, and cosmetics.
3. Provisional Listing of Lakes for Use in Drugs and Cosmetics
Part 82, subpart C, identifies the lakes that are provisionally
listed for general use in drugs and cosmetics. Section 82.1051
prescribes the certification requirements for these lakes, which may be
used both in ingested and externally applied drugs and cosmetics.
Externally applied drugs and cosmetics are those that are applied to
the external parts of the body and not to the lips or any body surface
covered by mucous membrane (Sec. 70.3(v) (21 CFR 70.3(v))).
Section 82.1051 specifies that lakes for use in drugs and cosmetics
are made by extending, on one or more listed substrata, one of the
listed straight colors with one or more of the listed precipitants. The
precipitant may be added either as a component of the listed straight
color, or alone to form the salt of the listed straight color. The
following substrata, alone or in any combination, are authorized for
use in lakes for drug and cosmetic use: Alumina, blanc fixe, gloss
white, clay, titanium dioxide, zinc oxide, talc, rosin, aluminum
benzoate, and calcium carbonate. The regulation also lists the
following cation precipitants for use in lakes for drug and cosmetic
use: Sodium, potassium, aluminum, barium, calcium, strontium, and
zirconium.
The regulation provides for the use of the following straight
colors in producing lakes for drug and cosmetic use: FD&C Blue No. 1
(Sec. 82.101); FD&C Blue No. 2 (Sec. 82.102); FD&C Green No. 3
(Sec. 82.203), FD&C Red No. 4 (Sec. 82.304); FD&C Yellow No. 5
(Sec. 82.705); FD&C Yellow No. 6 (Sec. 82.706); D&C Blue No. 4
(Sec. 82.1104), D&C Green No. 5 (Sec. 82.1205), D&C Orange No. 5
(Sec. 82.1255), D&C Red No. 6 (Sec. 82.1306), D&C Red No. 7
(Sec. 82.1307), D&C Red No. 21 (Sec. 82.1321), D&C Red No. 22
(Sec. 82.1322), D&C Red No. 27 (Sec. 82.1327), D&C Red No. 28
(Sec. 82.1328), D&C Red No. 30 (Sec. 82.1330), D&C Red No. 33
(Sec. 82.1333), D&C Red No. 34 (Sec. 82.1334), D&C Red No. 36
(Sec. 82.1336), D&C Violet No. 2 (Sec. 82.1602), and D&C Yellow No. 10
(Sec. 82.1710).
The regulations for lakes of D&C Red No. 33 (Sec. 82.1333), D&C Red
No. 36 (Sec. 82.1336) and FD&C Yellow No. 6 (Sec. 82.706) further
require that lakes of these straight colors for drug and cosmetic use
be prepared from previously certified batches of the straight colors.
Uncertified batches of the remaining straight colors may be used to
prepare lakes for drug and cosmetic use. Section 82.1051 also provides
specifications for ether extracts, soluble chlorides and sulfates, and
intermediates, and prescribes rules for naming lakes that are listed
for drug and cosmetic use.
4. Provisional Listing of Lakes for Use in Externally Applied Drugs and
Cosmetics
Part 82, subpart D, identifies the lakes that are provisionally
listed for use in externally applied drugs and cosmetics. Section
82.2050 prescribes the certification requirements for these lakes.
Section 82.2051 specifies that lakes for use in externally applied
drugs and cosmetics are made by extending, on one or more listed
substrata, one or more of the listed precipitants, and the straight
color Ext. D&C Yellow No. 7 listed in Sec. 82.2707a. The precipitant
may be added either as a component of the listed straight color, or
alone to form the salt of the listed straight color.
Although Ext. D&C Yellow No. 7 is the only straight color referred
to in subpart D, its lakes are not the only lakes limited to use in
externally applied drugs and cosmetics. As noted above, certain
straight colors that were provisionally listed for general drug and
cosmetic use were restricted to use in externally applied drugs and
cosmetics as part of their permanent listing. The agency also amended
the provisional listings for the lakes of these straight colors to
impose the same restrictions. The provisional listings of the following
color additives in subparts B and C of part 82 limit the use of their
lakes to externally applied drugs and cosmetics: FD&C Red No. 4
(Sec. 82.304); D&C Blue No. 4 (Sec. 82.1104), D&C Green No. 6
(Sec. 82.1206), D&C Orange No. 4 (Sec. 82.1254), D&C Orange No. 10
(Sec. 82.1260), D&C Orange No. 11 (Sec. 82.1261), D&C Red No. 17
(Sec. 82.1317), D&C Red No. 31 (Sec. 82.1331), D&C Yellow No. 7
(Sec. 82.1707) and D&C Yellow No. 8 (Sec. 82.1708).
The substrata, precipitants, and additional specifications listed
in
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Sec. 82.2051 for lakes used in externally applied drugs and cosmetics
are the same as those listed in Sec. 82.1051 for D&C lakes. Section
82.2051 also specifies that the listed names of Ext. D&C lakes are
derived in the same manner as for D&C lakes.
5. Permanently Listed Lakes of FD&C Red No. 40
The color additive FD&C Red No. 40 was not included in the
provisional list because FD&C Red No. 40 was not in use in 1960. In the
Federal Register of April 10, 1971 (36 FR 6892), the agency published a
final rule, in response to a color additive petition, permanently
listing FD&C Red No. 40 for use in food and drugs. The agency later
amended these regulations in response to another petition to provide
for use of the lakes of FD&C Red No. 40 in food and drugs (36 FR 23553,
December 10, 1971). Subsequently, in response to further petitions, the
agency published final rules expanding the listing of FD&C Red No. 40
to cosmetic uses. First, in the Federal Register of August 6, 1974 (39
FR 28278), the agency published a final rule permanently listing FD&C
Red No. 40 for use in dentifrices that are cosmetics. Subsequently, the
agency amended these regulations to expand the use of FD&C Red No. 40
and its lakes to cosmetics generally (39 FR 44198, December 23, 1974).
The permanent listings of FD&C Red No. 40 for food, drug, and
cosmetic use in Secs. 74.340, 74.1340, and 74.2340, respectively,
include its lakes. However, the permanent listings of these lakes cite
the provisional listings for lakes in part 82 for the preparation,
specifications, and labeling requirements applicable to FD&C Red No. 40
lakes. As a result, any agency action on the provisional listings for
lakes will affect the permanent listings for the lakes of FD&C Red No.
40. Therefore, this proposal includes consideration of the lakes of
FD&C Red No. 40.
C. The 1965 Proposal for Permanent Listing of Lakes and the 1979 Notice
of Intent
In the Federal Register of May 11, 1965 (30 FR 6490), the agency
proposed to list permanently certain lakes for use in foods, drugs, and
cosmetics under conditions similar to their current provisional
listing. However, because many straight colors were still provisionally
listed and because of the need for more information on lakes, the
agency, in 1979, terminated the rulemaking initiated by this proposal
without taking final action (44 FR 36411, June 22, 1979).
In the same issue of the Federal Register (44 FR 36411), the agency
published a notice that announced the agency's intent to repropose
regulations concerning lakes (the 1979 notice of intent (NOI)). The
agency also addressed the comments it had received in response to the
1965 proposal regarding the permanent listing of lakes. Three of the
five comments on the 1965 proposal recommended revising the regulations
to provide for the use of more than one previously certified batch of
color additive in the preparation of lakes for coloring drugs and
cosmetics. In the 1979 NOI, the agency stated its intention to consider
this recommendation in developing a new proposal for the permanent
listing of lakes. The agency also identified the following issues for
the scientific review of lakes: (1) The definition and nomenclature of
lakes; (2) the safety of lakes; and (3) the specifications for lakes
(stability and certification methodology). The agency requested
information and comments pertaining to these issues.
The agency received four comments on the 1979 NOI. These included
two brief responses from manufacturers and two extensive comments from
trade associations, the International Association of Color
Manufacturers (IACM) (formerly the Certified Color Manufacturers'
Association (CCMA)) and the Cosmetic, Toiletry, and Fragrance
Association, Inc. (CTFA). The issues raised by the agency in the 1979
NOI, along with the four comments received on that notice, and the
agency's responses to the comments, are discussed in the following
sections. This proposal does not, however, address comments related to
the straight colors that were provisionally listed in 1979 but have
been denied permanent listing in subsequent rulemakings (FD&C Red No. 3
(externally applied drug and all cosmetic uses), D&C Red Nos. 8, 9, and
19, and D&C Orange No. 17).
III. Development of Proposed Actions for Lakes
A. Terminology of Lakes
The agency is proposing the following changes to the existing
definitions relating to lakes.
1. Straight Color
Currently, Sec. 70.3(j) defines the term ``straight color'' as ``a
color additive listed in parts 73, 74, and 81 of this chapter, and
includes lakes * * *.'' Thus, the term encompasses all listed color
additives, including lakes. Current Sec. 70.3(l) defines the term
``lake'' as ``a straight color extended on a substratum by adsorption,
coprecipitation, or chemical combination that does not include any
combination of ingredients made by simple mixing process.'' These two
regulations, when read together, suggest that a lake may be used as a
color component of another lake. This implication is inconsistent with
current regulations for lakes (Secs. 82.51, 82.1051, and 82.2051) and
with the proposed regulations for lakes in this document, which do not
allow the synthesis of a lake using another lake as a color component.
There are other instances in which the existing definition of
straight color creates confusion. For example, the procedures for
requesting certification of a batch of a color additive treat straight
colors (Sec. 80.21(j)(1) (21 CFR 80.21(j)(1)) and lakes
(Sec. 80.21(j)(2)) separately. Federal Register publications relating
to color additives also commonly use the term ``straight color'' to
refer to a color additive other than a lake. For example, the 1979 NOI
referred to straight colors as distinct from lakes; the agency's
request for information concerning the usage of FD&C Red No. 3
requested data on straight colors, lakes, and mixtures (52 FR 44485;
November 19, 1987). Communications between the agency and industry also
indicate that the common usage of the term ``straight color'' does not
ordinarily include the term ``lake.'' To eliminate the confusion
resulting from the existing definition, the agency is proposing to
revise the definition for ``straight color.'' As revised, the
definition would read ``The term `straight color' means a color
additive that is listed in part 73 or 74 of this chapter, but does not
include color additive mixtures or lakes.''
2. Listed Color
As discussed in section III.A.1., the proposed definition of
``straight color'' would exclude lakes. Therefore, the agency is
proposing a new term ``listed color'' to refer to any color additive
(including a lake) listed in part 73 or 74 for any use. By definition,
the term would not include mixtures, which are not themselves listed
colors but rather combinations of listed colors. The agency is
proposing to add the following definition at Sec. 70.3(w): ``The term
'listed color' means a color additive listed in part 73 or 74 of this
chapter and includes lakes.''
3. Mixture
Currently, Sec. 70.3(k) defines the term ``mixture'' as ``a color
additive made by mixing two or more straight colors, or one or more
straight colors and one or
[[Page 8376]]
more diluents.'' The agency is proposing to modify this definition to
replace the current reference to ``straight color'' with ``listed
color'' and to clarify that a mixture does not involve a chemical
reaction between its components. Proposed Sec. 70.3(k) would read ``The
term `mixture' means a color additive made by mixing two or more listed
colors, or one or more listed colors and one or more diluents, without
an accompanying chemical reaction.''
4. Lake
Currently, Sec. 70.3(l) defines the term ``lake'' as ``a straight
color extended on a substratum by adsorption, coprecipitation, or
chemical combination that does not include any combination of
ingredients made by simple mixing process.'' As discussed in sections
IV. and V. of this document, the agency is proposing to permit the
preparation of a lake using more than one straight color. Proposed
Sec. 70.3(l) would read ``The term `lake' means a color additive made
by extending one or more straight colors on one or more substrata by
adsorption, coprecipitation, or chemical combination, but does not
include mixtures.''
5. Substratum
Currently, Sec. 70.3(n) defines ``substratum'' as ``the substance
on which the pure color in a lake is extended.'' This definition
implies that it is only the pure color that is extended on the
substratum. However, the data reviewed by the agency on the stability
of straight colors after laking clearly demonstrate that intermediates
and subsidiary colors are also extended on the substratum during the
laking process. Therefore, the agency is proposing to amend the
definition of substratum to read ``The term `substratum' means the
substance on which the straight color in a lake is extended.''
6. Precipitant (Basic Radical)
Although the term ``basic radical'' is not defined in the color
additive regulations, Secs. 82.51 and 82.1051 use ``basic radical'' to
denote a substance that may be used to precipitate a lake during its
manufacture. The agency believes that ``precipitant'' is a more
descriptive and scientifically accurate term for such a substance.
``Precipitant'' is the term normally used in technical publications.
For example, the Condensed Chemical Dictionary (12th ed., 1993) defines
a lake as a pigment produced by the interaction of an ``organic dye, a
precipitant, and an absorptive inorganic substrate.'' However, the same
source contains no definition of ``basic radical.'' The publications of
trade organizations also use the term ``precipitant'' rather than
``basic radical'' in discussions of lakes (Ref. 12). Therefore, the
agency is proposing to use the term ``precipitant'' rather than the
term ``basic radical'' in new Secs. 74.50 and 74.1050. However, the
agency is not proposing any formal definition of ``precipitant'' in
Sec. 70.3.
7. Repack
Currently, Sec. 70.3 does not define the term ``repack.'' However,
repacks are one of the four forms of color additive (in addition to
straight colors, lakes, and mixtures) that are certified under the
procedures in part 80. The other three forms of color additive are
defined in Sec. 70.3. Therefore, the agency tentatively concludes that
a definition of repack should be added to Sec. 70.3. Proposed
Sec. 70.3(x) would read ``The term `repack' means all or a portion of a
batch of certified color additive that has been sealed in accordance
with Sec. 70.20 and labeled in accordance with Sec. 70.25, but has been
either opened for repackaging without further processing, or relabeled
for shipment or delivery, by a person other than the person to whom the
certificate or acceptance of a notice claiming certification for the
batch was issued.'' Under Sec. 80.32(d), such repackaging or relabeling
results in the expiration of the certificate, and the batch therefore
ceases to be a certified batch. A repack may be certified under the
procedures in part 80 at a lower fee than for the original batch
(Sec. 80.10(b)). The agency notes that if a batch or portion of a batch
is processed in any way, including heating, then it is not a repack and
must be recertified as a new batch of color additive.
B. Nomenclature of Lakes
The current nomenclature system for lakes is described in
Secs. 82.51(b), 82.1051(b) and 82.2051(b). These regulations specify
that the listed name of a lake is formed from: (1) The listed name of
the color from which the lake is prepared; (2) the name of the cation
precipitant combined in such color; and (3) the word ``lake.'' This
system of nomenclature identifies the color additive as a lake and
specifies the straight-color component of the lake and the cation
precipitant used to prepare the lake. However, the name of a lake does
not identify the substrata used to prepare the lake. Because only one
substratum (alumina) is permitted in lakes for food use, this system
presents no identity problems for these lakes. However, under the
current nomenclature system, lakes listed for drug and cosmetic use are
not fully identified, because such lakes may contain a variety of
substrata. Thus, lakes produced from a common straight color and
cation, but different substrata, are identified with the same name. For
example, two lakes of D&C Red No. 21, one prepared with the cation
aluminum and the substratum alumina, the other with the cation aluminum
and the substrata alumina and titanium dioxide, are both named ``D&C
Red No. 21 Aluminum Lake.''
In the 1979 NOI, the agency described this problem with the current
nomenclature system and stated its intention to modify the nomenclature
system to include the substrata in the name of the lake. The agency
received comments from the IACM and CTFA supporting inclusion of
substrata in the name of a lake for the purpose of more accurately
identifying the listed color additive. As explained above, although
omitting the substratum from the name of a lake for food use presents
no problems, omitting the substratum from the name of a lake restricted
to drug or cosmetic use could cause confusion as to the identity of the
lake. However, as the same batch of lake may be used for a food, a
drug, or a cosmetic (if the lake is listed for all three uses), the
agency tentatively finds that use of a single nomenclature system to
identify all lakes would present the least overall confusion to users
of these color additives. Use of a uniform nomenclature system for all
lakes is also desirable because it avoids the necessity for
manufacturers of lakes to provide different labels for packages of the
same lake. Therefore, the agency is proposing that the same
nomenclature system be used for all lakes.
Therefore, the agency is proposing to modify the nomenclature of
lakes by requiring the inclusion of the identity of substrata in the
name of a lake. The proposed nomenclature system would construct the
name of a lake from the name(s) of the straight colors present in the
lake (in descending order of predominance), followed by the names of
the cations of the precipitants, and followed by the words ``Lake on
________ and ________'' (inserting the listed names of the substrata in
descending order of predominance). For example, the name of a lake
prepared by the extension of D&C Red No. 27 and D&C Orange No. 5 on
alumina and titanium dioxide using aluminum chloride and calcium
chloride as precipitants would be ``D&C Red No. 27 and D&C Orange No. 5
Aluminum Calcium Lake on Alumina and Titanium Dioxide.''
Currently, Sec. 82.1051(b)(1) provides that the name of a D&C lake
prepared
[[Page 8377]]
from an FD&C color shall be formed from the ``listed name of the color
from which the lake is prepared, except that if such name contains the
symbol `FD&C' such symbol shall be changed to `D&C'.'' For example, the
name of the lake formed from FD&C Yellow No. 5, rosin, and zirconium
cation is D&C Yellow No. 5 zirconium lake. The agency notes that the
use of the FD&C, D&C, and Ext. D&C prefixes to designate the approved
uses of colors originated in the 1939 listings of coal tar colors,
including lakes (4 FR 1922) and was carried over into the provisional
listing of these color additives in 1960 (25 FR 9759). The permanently
listed straight colors retained the names under which they were
provisionally listed, although the prefixes no longer accurately
reflected the approved uses in some cases. For example, FD&C Red No. 4
is permitted for use only in externally applied drug and cosmetic
products.
The agency is not proposing any action in this rulemaking to change
the names of the color additives whose food, drug, or cosmetic use is
no longer correctly designated by their FD&C or D&C prefix. However,
the agency has tentatively decided not to continue the current system
described in Sec. 82.1051(b)(1), in which the prefix `FD&C' is changed
to `D&C' when naming lakes for drug or cosmetic use that have been
prepared from straight colors that contain the `FD&C' prefix in their
name. The agency tentatively concludes that continuation of this
nomenclature provision is unnecessary to identify the approved uses of
the lake and could be confusing to users of lakes. As discussed above,
the designation `D&C' does not always accurately describe the uses of
the lake. Furthermore, under Sec. 70.25, the label of the color
additive must contain a declaration of the permitted uses of the lake.
Finally, because the proposed procedure for certification of lakes (see
section VI.B. of this document) would rely on the certificate for the
straight color used to prepare the lake, the agency believes that the
name of the lake should accurately identify the certified straight
color on which the certification of the lake is based. For example,
under the proposed certification procedure for lakes, the certificate
for the straight color in the lake cited above would be for ``FD&C
Yellow No. 5,'' not ``D&C Yellow No. 5.''
In the 1979 NOI, the agency also requested comments to address an
inconsistency in the current system of nomenclature; namely, that
certain lakes of identical composition may have different names. For
example, FD&C Blue No. 1 and D&C Blue No. 4 are two separately listed
straight colors that are different salt forms of the same dye. (FD&C
Blue No. 1 is the disodium salt and D&C Blue No. 4 is the diammonium
salt of a triphenylmethane derivative.) During the laking process the
accompanying cation in the straight color is replaced by the
precipitant cation. Thus, the lakes of these two straight colors,
prepared from the same substrata and precipitants, are chemically
identical. However, they have different names. For example, under the
current nomenclature system, the aluminum lakes on alumina of these two
straight colors are named ``FD&C Blue No. 1 Aluminum Lake'' and ``D&C
Blue No. 4 Aluminum Lake.'' (Under the proposed system, they would be
named ``FD&C Blue No. 1 Aluminum Lake on Alumina'' and ``D&C Blue No. 4
Aluminum Lake on Alumina,'' respectively.)
In its comment on the 1979 NOI, CTFA agreed with the agency's
assessment of this nomenclature problem. However, the comment suggested
that this and other problematic aspects of the current system of
nomenclature are better viewed as problems with the general
nomenclature of listed colors, not problems specific to lakes.
The agency agrees with CTFA's comment that these issues concerning
the nomenclature of lakes are really issues related to the general
nomenclature of listed colors. Therefore, the agency is not proposing
any modifications in the nomenclature of lakes to address these issues,
which are outside the scope of this rulemaking.
Under this proposal, the nomenclature proposed in this section
would be used for two purposes: (1) To prescribe the listed name of the
lake, because the agency is proposing to issue umbrella regulations for
lakes rather than an individual regulation for each listed lake; (2) to
identify the color additive on the labels of lakes that are packaged
for sale to manufacturers of foods, drugs, and cosmetics to be used in
coloring those products. The agency notes that lakes are also required
to be declared as ingredients on the label of foods and cosmetics.
Section VI.C.3. of this document describes the simplified nomenclature
system that FDA is proposing for ingredient labeling of lakes on food
and cosmetic labels.
Table 1.--Current and Proposed Regulatory Status of Straight Colors Used in Lakes
----------------------------------------------------------------------------------------------------------------
Current listings Proposed listings
----------------------------------------------------------------------------------------------------------------
Proposed regulatory
Current regulatory status Straight color status Straight color
----------------------------------------------------------------------------------------------------------------
Permanently listed: Part 74 FD&C Red No. 40....... Permanently listed: FD&C Blue No. 1, FD&C Blue
(Subpart A--Foods, Subpart B-- Part 74 (Subpart A-- No. 2, FD&C Green No. 3,
Drugs and Subpart C--Cosmetics). Foods (Sec. 74.50)). FD&C Red No. 40, FD&C
Yellow No. 5, FD&C Yellow
No. 6.
Provisionally listed:
Part 82 (Subpart B--Foods, FD&C Blue No. 1, FD&C (Subpart B--Drugs FD&C Blue No.1, FD&C Blue
Drugs, and Cosmetics). Blue No. 2, FD&C (Sec. 74.1050) and No. 2 (drugs only), FD&C
Green No. 3, FD&C Subpart C--Cosmetics Green No. 3, FD&C Yellow
Yellow No. 5, FD&C (Sec. 74.2050)).. No. 5, FD&C Yellow No. 6,
Yellow No. 6, FD&C FD&C Red No. 4, FD&C Red
Red No. 4. No. 40, D&C Blue No. 4,
D&C Orange No. 4, D&C
Orange No. 5, D&C Orange
No. 10, D&C Red No. 6, D&C
Red No. 7, D&C Red No. 21,
D&C Red No. 22, D&C Red
No. 27, D&C Red No. 28,
D&C Red No. 31, D&C Red
No. 33, D&C Red No. 34,
D&C Yellow No. 10.
[[Page 8378]]
(Subpart C--Drugs and FD&C Blue No. 1, FD&C Listing Terminated D&C Green No. 6, D&C Red
Cosmetics). Blue No. 2, FD&C (Does not form lakes). No. 17, D&C Red No. 30,
Green No. 3, FD&C D&C Red No. 36, D&C Violet
Yellow No. 5, FD&C No. 2.
Yellow No. 6, FD&C
Red No. 4, FD&C Blue
No. 4, FD&C Green No.
5, FD&C Green No. 6,
FD&C Orange No. 4,
FD&C Orange No. 5,
FD&C Orange No. 10,
FD&C Orange No. 11,
FD&C Orange No. 6,
FD&C Red No. 7, FD&C
Red No. 17, FD&C Red
No. 21, FD&C Red No.
22, FD&C Red No. 27,
FD&C Red No. 28, FD&C
Red No. 30, FD&C Red
No. 31, FD&C Red No.
33, FD&C Red No. 34,
FD&C Red No. 36, FD&C
Violet No. 2, FD&C
Yellow No. 7, FD&C
Yellow No. 8, FD&C
Yellow No. 10.
Listing Terminated (No D&C Green No. 5, D&C Orange
batches certified):. No. 11, D&C Yellow No. 7,
D&C Yellow No. 8.
(Subpart D-- Externally Applied Ext. D&C Yellow No. 7. Listing Terminated (No Ext. D&C Yellow No. 7.
Drugs and Cosmetics). confirmation of
stability during
laking).
----------------------------------------------------------------------------------------------------------------
C. Issues Relating to Definition of Lakes and Termination of Certain
Provisional Listings
1. Straight Colors
A summary of the current and proposed regulatory status of straight
colors for use in lakes is given in Table 1.
CTFA's comments on the 1979 NOI include information on the chemical
structure of the straight colors currently listed for use in lakes.
Based on its evaluation of these data and other information from the
published literature, the agency tentatively concludes that, to form a
lake, a straight color must contain a salt-forming group (i.e., a salt,
an acid, or a lactone group) as part of its chemical structure. The
agency finds that the following straight colors listed in part 82
contain a salt- forming group and thus are capable of forming a lake:
FD&C Red No. 4, D&C Red No. 6, D&C Red No. 7, D&C Red No. 21, D&C Red
No. 22, D&C Red No. 27, D&C Red No. 28, D&C Red No. 31, D&C Red No. 33,
D&C Red No. 34, FD&C Blue No. 1, FD&C Blue No. 2, D&C Blue No. 4, FD&C
Green No. 3, D&C Green No. 5, D&C Orange No. 4, D&C Orange No. 5, D&C
Orange No. 10, D&C Orange No. 11, FD&C Yellow No. 5, FD&C Yellow No. 6,
D&C Yellow No. 7, D&C Yellow No. 8, D&C Yellow No. 10, and Ext. D&C
Yellow No. 7.
However, based on the same information, the agency notes that the
following five straight colors listed in part 82 do not contain a salt-
forming group as part of their chemical structure and therefore cannot
form lakes: D&C Red No. 17, D&C Red No. 30, D&C Red No. 36, D&C Violet
No. 2, and D&C Green No. 6. CTFA's comment on the 1979 NOI also stated
that D&C Green No. 6 does not form a lake. Therefore, the agency
tentatively concludes that combinations of these straight colors with
substrata do not meet the definition of lake in Sec. 70.3(l).
Consequently, the agency is proposing to terminate the listing of D&C
Red No. 17, D&C Red No. 30, D&C Red No. 36, D&C Violet No. 2, and D&C
Green No. 6 as components of lakes. This proposed action would not
affect the listing of these color additives as straight colors. Under
the proposal, combinations of these straight colors with substrata that
are approved diluents or approved color additives would be color
additive mixtures rather than lakes. Such mixtures would be exempt from
certification under Sec. 80.35(b).
2. Diluents in Color Additive Mixtures for Cosmetic and Drug Use
a. Cosmetics. The agency notes that its proposed action to
terminate the listing of five straight colors as components of lakes
would not affect the use of these straight colors in cosmetic products.
Combinations of D&C Red No. 17, D&C Red No. 30, D&C Red No. 36, D&C
Violet No. 2, or D&C Green No. 6 with substrata listed in Sec. 82.1051
are color additive mixtures as defined in Sec. 70.3(k), and the
``substrata'' used in these combinations are diluents as defined in
Sec. 70.3(m). Because no regulation limits the diluents that may be
used in color additive mixtures intended for use in cosmetic products,
the proposed action to terminate the listing of D&C Red No. 17, D&C Red
No. 30, D&C Red No. 36, D&C Violet No. 2, and D&C Green No. 6 for use
in lakes would not affect their use in cosmetics as color additive
mixtures containing, as diluents, the substances now listed as
substrata in Sec. 82.1051 (alumina, blanc fixe, gloss white, clay,
titanium dioxide, zinc oxide, talc, rosin, aluminum benzoate, and
calcium carbonate).
b. Drugs. The proposed action to terminate the listing of D&C Red
No. 17, D&C Red No. 30, D&C Red No. 36, D&C
[[Page 8379]]
Violet No. 2, and D&C Green No. 6 for use in lakes would not affect
their use in drugs as color additive mixtures containing the following
substrata now listed in Sec. 82.1051: Alumina, calcium carbonate, talc,
titanium dioxide, and zinc oxide. Alumina, calcium carbonate, talc, and
titanium dioxide are listed in Secs. 73.1010, 73.1070, 73.1550, and
73.1575, respectively, as color additives exempt from certification for
use in drugs generally (ingested drugs and externally applied drugs).
Therefore, combinations of these substances with D&C Red No. 17, D&C
Red No. 30, D&C Red No. 36, D&C Violet No. 2, and D&C Green No. 6 are
permitted as color additive mixtures under existing regulations. Zinc
oxide is listed in Sec. 73.1991 as a color additive exempt from
certification for use in coloring externally applied drugs. In
addition, zinc oxide is generally recognized as safe (GRAS) for use as
a dietary supplement (Sec. 182.5991 (21 CFR 182.5991)) and as a
nutrient in food (Sec. 182.8991 (21 CFR 182.8991)). Section 73.1001
permits the use of substances listed in Sec. 73.1(a) as diluents in
color additive mixtures for ingested drug use. In turn, Sec. 73.1(a)
permits the use of substances that are GRAS under section 201(s) of the
act (21 U.S.C. 321(s)). Therefore, the agency concludes that zinc oxide
may be used with D&C Red No. 17, D&C Red No. 30, D&C Red No. 36, D&C
Violet No. 2, and D&C Green No. 6 either as an approved diluent in
color additive mixtures for coloring ingested drugs or as a straight-
color ingredient in color additive mixtures for coloring externally
applied drugs.
Rosin is currently listed in Sec. 73.1(b)(1)(i) as a diluent in
color additive mixtures for use in inks for marking food supplements in
tablet form, gum, and confectionery, and by reference, for use under
Sec. 73.1001(a)(2) in inks for branding pharmaceutical forms. In its
review of the safety of the substrata currently listed in Sec. 82.1051
(see section V.A.2.j. of this document), the agency determined that the
ingested uses of rosin are safe. However, in this same review, the
agency stated that it was aware of literature reports of dermal
irritation due to rosin (Ref. 13). Recently submitted data on human
skin sensitization and photoreaction to commercially available cosmetic
products colored with rosin lakes (Ref. 14) establish that lakes
containing rosin as a substratum are safe for externally applied drugs
and cosmetics. However, the rosin present in lakes, where it is a
component of an insoluble pigment, is not identical to free rosin
present as a diluent in color additive mixtures. Therefore, the agency
tentatively concludes that the data submitted on the safety of
externally applied rosin lakes do not resolve the safety issues
presented by the use of free rosin as a diluent in externally applied
drug products, such as the risk of allergic contact dermatitis and
occupational asthma.
Based on its safety review of rosin, the agency is proposing to
amend Sec. 73.1001 to list rosin as a diluent in color additive
mixtures for ingested drug use only. However, if the agency receives
information that adequately supports the safety of rosin as a diluent
in color additive mixtures for use in externally applied drugs, the
agency will consider listing rosin as a diluent for color additive
mixtures for both ingested and externally applied drugs. Anyone
interested in the listing of rosin for such use should submit
information on the identity, specifications, and dermal safety of the
rosin for which listing is sought.
The current regulations do not allow for the use of aluminum
benzoate, blanc fixe, clay, and gloss white as diluents in color
additive mixtures for drug use, because only the diluents provided for
in Sec. 73.1001 may be used in color additive mixtures for coloring
drugs. However, FDA has evaluated the safety of these substances, or
the materials used to make them, as part of its review of substrata in
lakes for drug and cosmetic use in section V.A.2. of this document.
This review included data on the ingested and dermal uses of barium
sulfate (blanc fixe), kaolin (clay), benzoic acid, and benzoates.
Specifically, the agency considered literature reviews of aluminum
salts, barium sulfate, kaolin and bentonite (a silicate); information
from the color additive petitions for use of certain aluminum lakes in
eye-area cosmetics; and safety reviews of aluminum compounds, benzoic
acid and benzoates, and kaolin and bentonite as food ingredients. These
safety reviews were conducted by the Select Committee on GRAS
Substances of the Federation of American Societies for Experimental
Biology and the Joint Food and Agriculture Organization (FAO)/World
Health Organization (WHO) Expert Committee on Food Additives.
Based on its review, which is discussed in section V.A.2. of this
document, the agency tentatively concludes that barium sulfate (blanc
fixe), aluminum benzoate, and kaolin (clay) are safe for use as
diluents in color additive mixtures for drug use. Therefore, as part of
its disposition of the provisional listings in part 82, the agency is
proposing to amend Sec. 73.1001 to list barium sulfate, aluminum
benzoate, and kaolin as diluents that may be safely used in color
additive mixtures exempt from certification that are intended for use
in ingested and externally applied drugs. The agency notes that gloss
white is a mixture of alumina and barium sulfate and thus would be
permitted for any use in color additive mixtures for which both alumina
and barium sulfate are permitted.
For the reasons discussed above, the agency tentatively concludes
that the proposed action to terminate the listing of D&C Red No. 17,
D&C Red No. 30, D&C Red No. 36, D&C Violet No. 2, and D&C Green No. 6
as components of lakes would not affect their use in drugs as color
additive mixtures containing alumina, calcium carbonate, kaolin (clay),
talc, zinc oxide, barium sulfate (blanc fixe), aluminum benzoate,
titanium dioxide, gloss white, or rosin (ingested drugs only). However,
the proposed termination would mean that those straight colors could no
longer be used in externally applied drugs as color additive mixtures
containing rosin, unless the agency receives data that establish the
safety of rosin as a diluent for externally applied uses.
3. Extended Toners
In the 1979 NOI, the agency requested information to identify
certain insoluble color additives, commercially described as extended
toners, that are classified as lakes under part 82. The agency
requested comments on the need to modify existing regulations or to
promulgate new regulations to address these color additives. FDA noted
its intent, in the absence of comments to the contrary, to exclude
these products from the definition of lakes.
CTFA's comment on the 1979 NOI provided information that identified
the composition of extended toners and of related insoluble color
additives known as resinated toners, extended resinated toners, and
toners. The comment requested revision of the definitions in 21 CFR
70.3 to better describe these substances. The agency has evaluated the
available information and determined that the color additives described
commercially as toners, resinated toners, extended toners, and extended
resinated toners are not lakes. These substances are either water-
insoluble straight colors or mixtures of water-insoluble straight
colors with insoluble diluents. Therefore, the agency tentatively
concludes that no new or modified regulations are needed to address
toners, resinated toners, extended toners, and extended resinated
[[Page 8380]]
toners because these substances are mixtures as defined in
Sec. 70.3(k), and the ``substrata'' used in these combinations are
diluents, as defined in Sec. 70.3(m).
The proposed reclassification of toners, resinated toners, extended
toners, and extended resinated toners as color additive mixtures
containing as diluents the ingredients now listed as substrata in
Sec. 82.1051 would not affect their use in drugs, because, as discussed
in section III.C.2. of this document, these substrata (except rosin for
use in externally applied drugs) are listed as GRAS in part 182, 184,
or 186 (21 CFR part 182, 184, or 186), approved as color additives for
drug use in part 73, or the agency is proposing to list them in
Sec. 73.1001 as diluents in color additive mixtures for drug use.
Because there is no regulation that limits the diluents that can be
used in color additive mixtures for cosmetic use, the proposed
reclassification of this group of color additives from lakes to color
additive mixtures would not affect their use in cosmetics.
4. Requests for Listing of Additional Lake Components
CTFA's comments on the 1979 NOI included a request that FDA
authorize for use in lakes the following straight colors: D&C Brown No.
1, D&C Green No. 8, and Ext. D&C Violet No. 2. These three straight
colors are currently listed in part 74 for cosmetic use. In addition,
D&C Green No. 8 is currently listed in part 74 for drug use. However,
the agency notes that these straight colors are not listed either
permanently in part 74 or provisionally in part 82 for use in preparing
lakes. Therefore, the agency tentatively concludes that consideration
of these straight colors for use in lakes is outside the scope of this
proposal, which addresses only the provisionally listed lakes and their
components. Interested persons may submit a color additive petition
under Sec. 71.1 (21 CFR 71.1) to amend the regulations to permit the
use of these straight colors in lakes.
CTFA's comments on the 1979 NOI also suggested that bismuth
oxychloride and mica should be listed as acceptable substrata in lakes
for coloring drugs and cosmetics. IACM's comments requested the listing
of titanium dioxide as a substratum for lakes for coloring foods.
However, bismuth oxychloride and mica are not provisionally listed in
part 82 as substrata in lakes for drug or cosmetic use, and titanium
dioxide is not provisionally listed in part 82 as a substratum in lakes
for food use. Therefore, the agency tentatively concludes that
consideration of the requested uses of these substances as substrata in
lakes is outside the scope of this rulemaking, which addresses
provisionally listed lakes and their components. Interested persons may
submit a color additive petition under Sec. 71.1 to amend the
regulations to permit use of these substances in lakes.
5. Definition of Lakes Versus Mixtures
CTFA's comments on the 1979 NOI noted that the straight-color
component of a lake, and not the substratum, provides the coloring
effect and, therefore, requested that the agency classify lakes as
color additive mixtures and list permitted substrata as diluents for
color additive mixtures.
As discussed in section III.C.1. of this document, the agency
agrees that combinations of non-salt-forming straight colors with
substrata should be classified as mixtures rather than lakes. As to
salt-forming straight colors, however, the agency disagrees with CTFA's
interpretation. Lakes are very different from color additive mixtures
because of the chemical reaction required to produce a lake. The agency
finds that, under both the current and proposed definitions of a lake,
the substratum is an integral part of the lake. In a mixture, there is
little if any chemical interaction between the components, which
function as separate ingredients. In the preparation of a lake,
however, there is a chemical reaction between the components, and the
physical properties of the resulting lake are very different from those
of the straight-color component (see section I. of this document).
Therefore, the agency tentatively concludes that lakes are not mixtures
and that substrata used to prepare a lake are not separate ingredients,
but are components of the finished color additive.
6. Pre-Amendments Certification of Provisionally Listed Lakes
As discussed in section II.A. of this document, the transitional
provisions of the 1960 amendments limited the provisional listing of
certifiable color additives to those for which at least one batch had
been certified prior to July 12, 1960, the enactment date of the 1960
amendments. In establishing the provisional list (25 FR 9759), FDA
removed 32 colors from listing because the agency had never certified
any batches of these colors. In preparing this document, the agency
reviewed its batch certification records to confirm that each straight
color, substratum, and precipitant included in the provisional listing
regulations for lakes was a component of at least one batch of a lake
certified between 1939 and July 12, 1960.
a. Straight Colors. The agency's search of color certification
records between 1939 and the enactment of the 1960 amendments
established that the agency did not certify any batches of lakes of D&C
Orange No. 11, D&C Yellow No. 7, D&C Yellow No. 8, or D&C Green No. 5
during that time. The agency tentatively concludes that its original
provisional listing of these color additives for use in lakes for drugs
or cosmetics was therefore incorrect. Accordingly, the agency is
proposing to terminate the provisional listings of D&C Orange No. 11,
D&C Yellow No. 7, D&C Yellow No. 8, and D&C Green No. 5 as components
of lakes for use in drugs or cosmetics. Any future consideration of the
use of these color additives as components of lakes would be through
the color additive petition process (Sec. 71.1).
b. Substrata. The agency's color certification records show that
all of the substrata listed in Secs. 82.51, 82.1051, and 82.2051,
except calcium carbonate, have been in continuous use in lakes because
certification was initiated in 1939 (Ref. 15). The agency added calcium
carbonate to the list of permitted substrata in 1959 (24 FR 3818) and
certified at least one batch of a lake containing this substratum for
drug or cosmetic use before the enactment of the 1960 amendments.
c. Precipitants. Section 82.51 lists two cations (calcium and
aluminum) as components of precipitants in lakes for food use. The
agency certified batches of FD&C aluminum lakes before the enactment of
the 1960 amendments. However, in the 1979 NOI, the agency proposed to
delete calcium as a listed cation in lakes for food use because the
agency had never certified any batches of FD&C calcium lakes.
Comments on the 1979 NOI from IACM and CTFA requested the agency
not to take this action. However, because these comments provided no
information to document agency certification of any batches of FD&C
calcium lakes before the enactment of the 1960 amendments, the agency
tentatively concludes that its original provisional listing of these
lakes was incorrect. Therefore, the agency is proposing to terminate
the provisional listing of calcium as a precipitant in the preparation
of lakes for food use. Any future consideration of the use of lakes
containing calcium precipitants for coloring food would be through the
color additive petition process (Sec. 71.1).
Sections 82.1051 and 82.2051 list seven cations (sodium, potassium,
aluminum, barium, calcium, strontium, and zirconium) as components of
precipitants in lakes for drug or cosmetic use. The agency certified
[[Page 8381]]
batches of lakes containing each of these seven cations for drug or
cosmetic use before the enactment of the 1960 amendments.
IV. Safety Review and Proposed Actions for Lakes for Use in Foods
A. Review of Components of Lakes for Use in Foods
The current regulation for provisionally listed lakes for use in
foods (21 CFR 82.51) provides for use of the following components in
such lakes: (1) Certified batches of the straight colors FD&C Blue No.
1 (21 CFR 82.101), FD&C Blue No. 2 (21 CFR 82.102), FD&C Green No. 3
(21 CFR 82.203), FD&C Yellow No. 5 (21 CFR 82.705), FD&C Yellow No. 6
(21 CFR 82.706); (2) the substratum alumina; (3) precipitants
containing the cations aluminum (Al+3) and calcium (Ca+2).
Additionally, 21 CFR 74.340 permanently lists lakes of FD&C Red No. 40
that are prepared as described in 21 CFR 82.51 and that meet the
specifications and labeling requirements prescribed by Sec. 82.51.
The identity and specifications for the straight colors used in the
preparation of the provisionally listed lakes for food use are provided
in the regulations for the straight-color components of lakes in part
82, which are cited above. The regulations in part 82 cross-reference
the permanent listings of the straight colors in part 74. As to
substrata, Sec. 82.3 defines alumina, but provides no specifications
for alumina or for the materials used to prepare it in situ. Finally,
with regard to precipitants, part 82 does not identify or prescribe
specifications for the precipitants that may be used in the preparation
of these lakes, other than specifying the cation component and
providing specifications that limit the level of soluble chlorides and
sulfates in the lake.
1. Straight Colors
a. Identity. The agency has already reviewed the identity and
safety of the straight colors currently permitted as components of
lakes for food use, either as part of its scientific review of
provisionally listed straight colors or in response to petitions for
the review of new color additives. Based on these reviews, the agency
concluded that FD&C Blue No. 1, FD&C Blue No. 2, FD&C Green No. 3, FD&C
Yellow No. 5, FD&C Yellow No. 6, and FD&C Red No. 40 are safe for use
in foods and permanently listed these straight colors in 21 CFR part
74, subpart A. The agency is proposing to continue to permit the use of
these straight colors as components of lakes for use in food, subject
to the proposed requirements discussed below.
b. Use of previously certified batches. Currently, under
Sec. 82.51, manufacturers are required to prepare lakes for food use
from previously certified batches of straight colors. This requirement
was intended to ensure that the levels of intermediates, subsidiary
colors, and other impurities in straight colors that are used to
prepare lakes for food use are within the levels specified in the
applicable regulations. Impurities in the straight color, especially
the carcinogenic constituents present in some straight colors, are a
primary safety concern with the use of these color additives and their
lakes in food.
In the 1979 NOI, the agency requested submission of information
about available methods for the determination of total (free plus
bound) intermediates, as well as subsidiary colors and other
impurities, and stated that without appropriate analytical methodology
it might be necessary to require that all lakes be produced from
certified batches of straight colors. The agency stated that there was
no satisfactory analytical method to determine total intermediates in
lakes. The available methods detected free intermediates but not
necessarily the intermediates that, like the straight color, are bound
to the substratum.
The comments on the 1979 NOI did not provide suitable methodology
for the analysis of intermediates and other impurities in lakes. CTFA's
comment stated that these problems could be addressed only through a
time-consuming and difficult undertaking to develop satisfactory
analytical methods. The comment suggested that the issue of
certification methodology should be separated from that of the
permanent listing of lakes, thus allowing these lakes to be permanently
listed while the industry and the agency went on to address the issue
of certification methodology jointly.
Section 721(b)(5)(A)(iv) of the act provides that in determining
whether the proposed use of a color additive is safe, the agency must
consider, among other relevant factors, the availability of any needed
practicable methods of analysis for determining the identity and
quantity of intermediates and other impurities contained in the color
additive. If lakes are prepared from uncertified batches of straight
colors, the only way to ensure that the intermediates, subsidiary
colors, and other impurities derived from the straight color do not
exceed the specification limits for the lake is to analyze the lake
itself for those impurities. However, as indicated above, the
analytical methods to accomplish this purpose are not currently
available. Therefore, the agency tentatively concludes that the lack of
adequate analytical methods to determine the levels of intermediates
and other impurities in lakes precludes the agency from prescribing
conditions of safe use for lakes prepared from uncertified batches of
straight colors. Accordingly, to ensure the continued safety of lakes
for food use, the agency is proposing to retain the requirement that
these lakes be prepared from certified batches of straight colors. As
discussed in section V.A. of this document, FDA is also proposing to
require that lakes for use in drugs and cosmetics be prepared from
certified batches of straight colors.
c. Stability. In the 1979 NOI, the agency asked for information
about the chemical stability of straight colors during the laking
process. The agency stated that if previously certified batches of
straight colors are used in the preparation of lakes, the levels of
intermediates and subsidiary colors in these lakes should be
proportional to those in the original batch of the straight color.
However, the agency was concerned that the laking process could cause
an unstable straight color to deteriorate and, consequently, increase
the levels of intermediates and subsidiary colors.
The agency requested data to confirm the stability of previously
certified batches of straight colors during the laking process. The
agency stated that, if such data were submitted, the agency would not
require specifications for intermediates and subsidiary colors in lakes
prepared from certified batches of straight colors. The agency also
noted the lack of satisfactory methodology for identifying and
quantifying intermediates and certain other contaminants in many lakes,
but added that the lack of such methodology does not pose a problem for
lakes produced from previously certified batches of colors, provided
that there is no measurable degradation of the color during the laking
process.
The straight colors that FDA proposes to permit as components of
lakes for food use fall into the following four groups, based on
chemical structure (the Color Index Structural classification (Ref.
16), as further refined by Marmion (Ref. 17)): Monoazo (FD&C Red No.
40, FD&C Yellow No. 6); pyrazolone (FD&C Yellow No. 5);
triphenylmethane (FD&C Blue No. 1, FD&C Green No. 3); and indigoid
(FD&C Blue No. 2). The FD&C lakes of these straight colors made up
about 80 percent of the total poundage of lakes certified in fiscal
year 1995 (FY-95) (Ref. 18). FD&C lakes of three
[[Page 8382]]
straight colors (FD&C Yellow No. 5, FD&C Yellow No. 6, and FD&C Red No.
40) made up about 90 percent of the FD&C lakes certified in FY-95.
Lakes of FD&C Blue No. 1 and FD&C Blue No. 2 made up the remaining 10
percent. No batches of FD&C Green No. 3 lakes were certified in FY-95.
Because lakes of monoazo and pyrazolone dyes make up such a high
proportion of lakes certified, the agency is particularly concerned
about possible degradation of FD&C lakes of these dyes.
CTFA submitted data (Ref. 19) to confirm the stability during
laking on alumina of three straight colors (FD&C Blue No. 1, FD&C Red
No. 40, and FD&C Yellow No. 5) that represent three of the four
structural groups. The data presented a comparison of the high
performance liquid chromatography (HPLC) evaluations of each of five
samples of FD&C Red No. 40, FD&C Yellow No. 5, and FD&C Blue No. 1 with
the corresponding lake made from each sample. FDA has evaluated the
data submitted by CTFA. A quantitative comparison of the levels of
intermediates and subsidiary colors present in the straight color and
the corresponding lake confirmed that the levels of intermediates and
subsidiary colors in the lakes (after adjustment for the percent
straight color in the lake) did not differ significantly from those in
the corresponding straight colors (Ref. 20).
The agency also conducted a brief study on the stability of FD&C
Blue No. 2 during the laking process (Ref. 21). This study presented a
comparison of the HPLC evaluations of a sample of a certified batch of
FD&C Blue No. 2 and a sample of a certified batch of the aluminum lake
prepared from this batch. A quantitative comparison of the levels of
intermediates and subsidiary colors present in the straight color and
the corresponding lake confirmed that the levels of intermediates and
subsidiary colors in the lake (after adjustment for the percent
straight color in the lake) did not differ significantly from those in
the corresponding straight color.
The data evaluated by the agency provide evidence that lakes of the
straight colors FD&C Yellow No. 5, FD&C Red No. 40, FD&C Blue No. 1,
and FD&C Blue No. 2 can be produced without significant degradation of
the straight color. When produced under conditions of current good
manufacturing practice (CGMP), these lakes meet the specifications for
intermediates and subsidiary colors in the straight color, after
adjustment for total color content of the lake. Although data have not
been submitted for all of the straight colors FDA proposes to permit as
components of lakes for food use, the remaining such straight colors
(FD&C Green No. 3 and FD&C Yellow No. 6) have chemical structures that
are similar to other straight colors (FD&C Blue No. 1 and FD&C Red No.
40, respectively) discussed above. The stability of FD&C Yellow No. 6
aluminum lake, which makes up over 25 percent of the total poundage of
FD&C lakes certified in FY-95, is also supported by published studies.
In these studies, the FD&C Yellow No. 6 aluminum lake showed greater
thermal stability than did FD&C Red No. 40 aluminum lake (Ref. 22), and
the straight color FD&C Yellow No. 6 was as stable as the straight
color FD&C Red No. 40 under the pH conditions studied, showing no
appreciable change over a week's exposure (Ref. 17). The agency
tentatively finds that because of the similarity of chemical structure,
the data available for the lakes of FD&C Blue No. 1 and FD&C Red No. 40
are adequate to confirm the stability of FD&C Green No. 3 and FD&C
Yellow No. 6, respectively, during the manufacture of lakes in
accordance with CGMP. In addition, the published data on FD&C Yellow
No. 6 and its aluminum lake provide corroborative evidence for the
stability of this straight color during the laking process when
conducted under conditions consistent with CGMP.
Based on its previous evaluations of the safety of the straight
colors that FDA proposes to permit as components of lakes for food use
and on the scientific evidence that lakes of these straight colors can
be produced under conditions consistent with CGMP without significant
degradation of the straight color, the agency now tentatively concludes
that certified batches of FD&C Blue No. 1, FD&C Blue No. 2, FD&C Green
No. 3, FD&C Yellow No. 5, FD&C Yellow No. 6, and FD&C Red No. 40 are
safe for use as components of lakes for food use that are prepared
under conditions of CGMP. Therefore, the agency is proposing to permit
certified batches of these straight colors as components of lakes for
food use in Sec. 74.50.
The agency is not, however, proposing to establish any definition
of CGMP for the preparation of lakes for food use. FDA recognizes that
CGMP for laking will vary with the straight color used, may include a
variety of combinations of conditions, and may change over time with
the introduction of new combinations of conditions. The agency's
regulatory goal is to protect the public health by assuring that laking
is conducted in a manner such that no significant degradation of the
straight color occurs, not to prescribe the details of industry
practice. Safety issues relating to the use of CGMP in preparing lakes
are discussed further in sections IV.B.5 and IV.C. of this document.
d. Use of more than one straight color in a lake. The agency also
tentatively concludes that the current prohibition on the use of more
than one straight color in a lake is unnecessary. This prohibition was
instituted as part of the original listing of lakes as certified colors
in 1939 (4 FR 1922, 4 FR 3931, and 5 FR 1138). At that time, the
regulations did not require that lakes be prepared from previously
certified batches of straight color, and the only food use for which
lakes were listed was for dyeing eggs in the shell. The requirement
that lakes for food use be prepared from previously certified batches
of straight color was initiated in 1959, when the regulations were
amended to permit, for the first time, the use of certain lakes in
foods generally (24 FR 3818 and 24 FR 5302). The agency now tentatively
concludes that, because of the proposed requirement that certified
batches of straight colors be used in preparing all lakes, the evidence
for the stability of straight colors during the laking process, and the
proposed certification requirement for lakes (discussed in section
IV.C. of this document), the prohibition against the use of more than
one straight color to make a lake is unnecessary. Therefore, the agency
is proposing to permit the preparation of a lake from certified batches
of more than one straight color.
2. Substratum--Alumina
Alumina is the only substratum provisionally listed for lakes for
food use. Section 82.3(g) defines alumina as ``a suspension in water of
precipitated aluminum hydroxide'' but prescribes no quality
requirements for alumina substratum. This definition covers both
preformed (precipitated and dried) alumina that is subsequently
suspended in water and alumina that is prepared in situ, without
subsequent recovery and drying.
As noted in section I. of this document, alumina may be prepared in
situ from aluminum sulfate and sodium hydroxide or sodium carbonate
during the manufacture of lakes. Aluminum sulfate is GRAS for food use
(Sec. 182.1125) and is subject to the specifications in the Food
Chemicals Codex 2d. ed. (1972) (Sec. 170.30(h)(1) (21 CFR
170.30(h)(1))). Sodium carbonate and sodium hydroxide are affirmed as
GRAS for food use (Secs. 184.1742 and 184.1763, respectively) and are
required
[[Page 8383]]
to meet the specifications in the Food Chemicals Codex, 3d. ed. (1981).
In addition, Sec. 73.1010 lists alumina (dried aluminum hydroxide)
as a color additive for use in drugs and provides identity and
specifications for alumina as a color additive. The agency tentatively
concludes that, although the listed use of alumina (dried aluminum
hydroxide) is for coloring drug products, alumina that meets the
identity and quality requirements in Sec. 73.1010 (a)(1) and (b) is
safe as a substratum for lakes for food use (Ref. 13).
The agency has evaluated the available data relating to the safety
of aluminum salts. These data included literature reviews, information
from a color additive petition for use of several aluminum lakes on
alumina in eye-area cosmetics, and safety reviews of aluminum compounds
(including aluminum salts) as food ingredients by the Select Committee
on GRAS Substances of the Federation of American Societies for
Experimental Biology and the Joint FAO/WHO Expert Committee of Food
Additives. Based on this evaluation, the agency tentatively concludes
that alumina conforming to the identity and quality requirements set
forth in Sec. 73.1010 (a)(1) and (b) (Refs. 13, 23, and 24) is safe for
use as a substratum in lakes for food use. The agency also tentatively
concludes that alumina prepared from aluminum sulfate and sodium
carbonate or sodium hydroxide that meet the requirements for these
compounds in the Food Chemicals Codex 2d ed. (1971) (aluminum sulfate)
or 3d ed. (1981) (sodium carbonate and sodium hydroxide) is safe as a
component of lakes for food use.
3. Precipitants
a. Aluminum cation (Al+3). In its safety review of alumina
(see section IV.A.2. of this document), the agency evaluated the safety
of the use of the aluminum salts (salts containing the aluminum cation
(Al+3)). Based on this safety review, the agency tentatively
concluded that the use of alumina as a substratum in lakes is safe.
Based on the same data, the agency also tentatively concludes that the
use of the aluminum cation as a component of precipitants used in the
preparation of lakes for food use is safe (Ref. 13, 23, and 24).
Aluminum cation is added as a precipitant with an accompanying anion.
If an aluminum salt is added as a precipitant, the anion is added as
part of the salt. Alternatively, if aluminum oxide or hydroxide is used
as a precipitant, the anion is added as an acid to ensure the
solubility of the aluminum cation to function as a precipitant. The
anions that the agency proposes to permit for use in lakes are
discussed in section IV.A.3.c. of this document.
The agency is not proposing to establish quality requirements for
precipitants used in the preparation of lakes for food use. The agency
recognizes that a variety of precipitant ingredients can be used to
produce the aluminum cation that functions as a precipitant in lakes
for food use. Furthermore, the agency does not anticipate that the use
of precipitant ingredients that form the aluminum cation, under
conditions consistent with CGMP, would introduce contaminants that
require limitation by specifications for the precipitant ingredients.
Precipitants are used at low levels (a small percentage of the total
batch weight) and, by virtue of their function in the laking process,
are always water-soluble cations. Because lakes are washed when
prepared in accordance with CGMP, the agency anticipates that only low
levels of water-soluble contaminants will remain in the finished lake.
The only possible concern would be the presence of heavy metals
deriving from contaminants in the precipitants. To address this
potential problem, as discussed below, the proposed specifications for
lakes will limit the levels of heavy metal contaminants permitted in
the end product. Therefore, the agency tentatively concludes that
quality requirements for the ingredients used to form precipitants in
lakes for food use are unnecessary.
b. Calcium cation (Ca+2). As discussed in section III.C.6.c.
of this document, the agency is proposing to terminate the listing of
calcium as a cation in lakes for food use because calcium lakes were
not used in food in 1960 and thus should not have been provisionally
listed. Any future consideration of the use of calcium lakes for
coloring foods would be through the color additive petition process
(Sec. 71.1).
c. Accompanying anions. The use of the aluminum cation in
preparation of lakes results in the formation of chloride or sulfate
anions. Chloride and sulfate are components of many food ingredients
that the agency has listed or affirmed as GRAS for general food use
(for example: Aluminum sulfate, Sec. 182.1125; calcium sulfate,
Sec. 184.1230; table salt (sodium chloride), Sec. 182.1(a); potassium
chloride, Sec. 184.1622). In the safety reviews conducted as part of
the GRAS rulemakings for these ingredients, the agency found that
ingestion of chloride and sulfate (in the presence of the accompanying
cation) was safe at levels that vastly exceed possible levels of
exposure to these anions as components of lakes. Therefore, the agency
tentatively concludes that the presence of these anions in lakes for
food use is safe when CGMP is observed (Ref. 13).
B. Specifications for Lakes for Use in Foods
1. Intermediates and Other Impurities Derived From Straight Colors
A typical straight color contains, in addition to the primary color
component, intermediates and subsidiary colors. Intermediates are
unreacted starting materials used to synthesize the primary color.
Subsidiary colors are colored by-products of the synthesis of the
primary color. As discussed in section IV.A.1.b. of this document, the
agency is proposing to require that lakes be prepared from certified
batches of straight color. The regulations for straight colors contain
specifications that limit the levels of intermediates and subsidiary
colors that may be present in the straight color. In this proposal, the
agency has also tentatively concluded that the straight colors in lakes
for food use do not degrade significantly during preparation of the
lakes under conditions consistent with CGMP. Therefore, the agency
tentatively concludes that the specifications for intermediates and
subsidiary colors in straight colors are sufficient to ensure the
safety of lakes prepared from certified batches of straight colors and
that separate specifications for intermediates and subsidiary colors in
lakes are unnecessary.
2. Heavy Metals
The current specifications for lakes for food use (Sec. 82.5)
establish limits of 10 ppm lead, 1.4 ppm arsenic, and ``not more than
trace'' levels of total heavy metals (other than lead and arsenic). In
the 1979 NOI, the agency proposed adding a specification for mercury in
lakes. The agency tentatively finds that the manufacturing processes
for lakes use metal salts that are sources of potential contamination
by heavy metals; moreover, in its certification of lakes, the agency
has rejected batches because of the presence of heavy metals, including
lead. Therefore, the agency tentatively concludes that specifications
to limit the levels of lead, arsenic, and mercury in lakes are
necessary to ensure their safe use in food. As a result of its safety
reviews of the straight colors used in food, the agency established
limits of not more than 10 parts per million
[[Page 8384]]
(ppm) lead, 3 ppm arsenic, and 1 ppm mercury in the specifications for
most color additives permanently listed for food use in parts 73 and
74. The agency tentatively concludes that such specifications are also
sufficient to ensure the safety of lakes.
FDA is unaware of any heavy metals, other than lead, arsenic, and
mercury, that have a significant level of toxicity and that would be
expected to occur in lakes. Therefore, the agency tentatively concludes
that a general heavy metal specification is unnecessary to ensure the
safety of lakes for food use.
One comment received in response to the 1979 NOI suggested that a
limitation on iron be included in the specifications for lakes for food
use. Iron salts may be present in lakes as contaminants inadvertently
introduced during the manufacturing process. For example, a batch of
lake prepared using rusted equipment or water with a high iron content
may contain iron salts.
The agency has evaluated the safety of iron salts as a contaminant
in lakes to determine whether their presence would present a sufficient
safety hazard to warrant inclusion of a specification for iron. The
agency notes that iron is an essential mineral, and that iron and many
of its salts are affirmed as GRAS in part 184 for use as nutrients in
food (for example, elemental iron, Sec. 184.1375; ferric ammonium
citrate, Sec. 184.1296; ferric chloride, Sec. 184.1297; ferric sulfate,
Sec. 184.1307; ferrous carbonate, Sec. 184.1307b; ferrous sulfate,
Sec. 184.1315). However, the agency also notes that high levels of iron
consumption can be toxic, especially for certain subpopulations. (See,
e.g., 59 FR 51030, October 6, 1994).
Lakes are generally used at low levels (typically less than 0.05
percent) in foods, except for some low-consumption food items such as
candy and candy coatings, colored sugar and frostings, dietary
supplements, seasonings, flavorings, and chewing gum (Ref. 25).
Therefore, consumption of iron due to its presence in lakes as a
contaminant would be low. Under these circumstances, the agency finds
no evidence of a safety hazard from exposure to iron as a contaminant
in lakes for food use. Therefore, the agency tentatively concludes that
a specification to limit the level of iron is unnecessary to ensure the
safety of lakes for food use. Moreover, the agency notes that the
conditions and practices that lead to the presence of iron salts as a
contaminant in a batch of lake are addressed by the proposed
requirement that lakes be prepared in accordance with CGMP (see section
IV.B.5. of this document).
3. Soluble Chlorides and Sulfates
Current Sec. 82.51 contains a specification that limits the content
of the soluble chloride and sulfate anions in lakes for food use. The
agency finds that the washing of the lake during the manufacturing
process removes most of these water-soluble anions. Furthermore, as
discussed above in section IV.A.3.c. of this document, the agency found
in safety reviews conducted as part of several GRAS rulemakings that
soluble chloride and sulfate anions are safe in foods at levels
considerably greater than those found in lakes (Ref. 13). Therefore,
the agency tentatively concludes that a specification to limit the
levels of soluble chlorides and sulfates is unnecessary to ensure the
safety of lakes prepared in conformity with CGMP for food use.
4. Inorganic Material Insoluble in HCl
Current Sec. 82.51 contains specifications that limit the content
of inorganic material insoluble in HCl in lakes. This specification was
intended to ensure that the lake was prepared in accordance with CGMP
and that no foreign material was inadvertently added during the laking
process. However, agency certification records for lakes for food use
in the past 20 years show that only one batch of lake has been denied
certification based on this specification. Even without the
specification for inorganic material insoluble in HCl, this batch of
lake would not have met the requirements in this proposal because the
alumina used as a substratum would not have met the applicable quality
requirements. Furthermore, the agency is proposing to include in the
specifications for lakes a provision to require that lakes be prepared
in accordance with CGMP. Therefore, the agency tentatively concludes
that a specification for material insoluble in HCl is unnecessary for
lakes that meet the other proposed requirements for lakes, and such a
specification is not included in this proposal.
5. Other Impurities and Contaminants
The agency has tentatively concluded above that specifications to
limit the level of total heavy metals (except lead, arsenic, and
mercury), soluble chlorides and sulfates, and material insoluble in HCl
are unnecessary to ensure the safety of lakes for food use as long as a
general provision is included in the specifications for lakes to ensure
that they are prepared in conformity with CGMP. The identity
requirements and specifications in color additive regulations include
impurities that are expected to occur at significant levels in a color
additive that has been prepared in accordance with CGMP. In its
certification of color additives, FDA has occasionally denied
certification for batches of color additives due to the presence of
significant levels of impurities for which the listing regulation
contains no specifications. In a few instances, these impurities could
be linked to improper storage of the color additive or to cross-
contamination from insufficiently cleaned processing equipment. In most
cases, the source of the impurity was unknown. Based on the agency's
experience in certifying thousands of batches of color additives
annually, corroborated by the agency's analyses of reference standards
(reference batches of color additives) used in toxicological studies of
various straight colors as part of the safety reviews of these color
additives, FDA believes that the impurities in the rejected batches
would not have been present had the color additives been manufactured
under conditions consistent with CGMP.
As noted above in section IV.A.1.c. of this document, it is
important that lakes be prepared in accordance with CGMP to ensure that
the straight color does not degrade during preparation of the lake.
Manufacturing conditions must be controlled so that levels of uncolored
components in the straight color, including the carcinogenic
constituents in certain monoazo and pyrazolone straight colors, do not
increase during preparation or handling of the lake. CGMP includes use
of proper temperatures, especially during drying, to avoid affecting
the composition of the lake, and sufficient washing of the lake to
remove water-soluble impurities. For example, the agency recently
rejected a batch of a monoazo straight color because the batch exceeded
the specifications for certain carcinogenic constituents. Subsequent
discussions with the manufacturer revealed that the batch had been
previously certified, but had failed to meet the manufacturer's
microbiological specifications and had been reprocessed (redried).
After redrying, the batch no longer met the specification for trace-
level carcinogenic constituents. The agency notes, however, that
because of their chemical properties, such carcinogenic constituents
are unlikely to be incorporated into lakes to the same extent as into
straight colors, and sufficient washing of the lake could significantly
decrease the levels of these constituents.
To ensure the safety of lakes for use in foods, FDA is proposing to
continue
[[Page 8385]]
the requirement in existing Sec. 82.5 that lakes shall be free from
impurities other than those named in the specifications, to the extent
that such impurities may be avoided by CGMP. However, the agency is not
proposing to define specific conditions that would constitute CGMP in
the preparation of lakes. The agency recognizes that appropriate
manufacturing conditions may differ for the preparation of different
lakes and, in fact, may change over time. Furthermore, even the
preparation of a single lake that meets the requirements of part 74 may
be accomplished using different conditions of manufacture. The agency
wants to retain the current flexibility in preparation of lakes for
food use, but maintain the assurance that there will be no significant
degradation of the straight color during preparation of the lake and
that the resulting lake will be otherwise in compliance with the
requirements of part 74. To accomplish this objective, the agency is
not proposing to define any specific conditions of CGMP; however, in
its review of notices claiming certification for batches of lake, the
agency is proposing to use the accountability of the straight color in
the lake, calculated as described below, as an indicator of the use of
CGMP in the preparation of the lake.
Under the current certification procedure for FD&C lakes, the
agency can monitor both the use of certified batches of straight color
in lakes for food use and indicators for the use of CGMP in the
preparation or repack of a batch of lake. In a request for
certification for a batch of lake, the firm must declare the certified
lot number and the poundage from that lot for the straight color that
is added to prepare the lake. The agency can determine a poundage
accountability of the batches of straight colors that are used to
prepare FD&C lakes. This accountability ensures that no more straight
color is used in FD&C lakes than has been certified. For example, a
firm that owns a 100-pound batch of straight color cannot credibly
claim to use 1,000 pounds from that batch to make lakes.
From the information in the request for certification and from
analysis of the sample submitted with the request, the agency
determines the total color accountability for each batch of lake (the
amount of total color that was added to the batch of lake compared to
the total color of the resulting batch). This accountability for total
color is an indicator for the use of CGMP in the preparation or repack
of a batch of lake. In its determination of accountability of the
straight color in lakes for food use, the agency calculates a
theoretical range for the expected total color content of a lake based
on the minimum total color permitted in the listing regulation for the
straight color, the maximum total color possible for the straight color
(100 percent), the weight of straight color used to prepare the lake,
and the weight of the lake. For example, for a 100-pound batch of FD&C
Yellow No. 5 aluminum lake on alumina that was prepared from 25 pounds
of FD&C Yellow No. 5, the theoretical range for the expected total
color content of the lake would be from 21.8 percent to 25 percent.
This theoretical range allows for variations in total color resulting
from factors that normally occur during the manufacture of a lake, such
as incomplete laking of the color and bleeding of the color during
washing.
The agency is requesting comments on the usefulness of total color
accountability as an indicator of the use of CGMP in the preparation
and repacking of batches of lake.
C. Certification Requirement
The agency has evaluated the necessity, in the interest of public
health, for the certification of lakes prepared from certified batches
of straight color. The agency tentatively concludes that continued
batch certification of lakes is necessary to protect the public health.
The agency bases this tentative conclusion on two safety issues: The
need to ensure the safety of the components (straight colors,
precipitants, and substrata) used to prepare a lake; and the need to
ensure that lakes are prepared and repacked under conditions of CGMP to
prevent degradation of the straight color.
The agency's traditional means for postmarket assurance of product
safety is the collection and analysis of a sample. However, as
discussed in section IV.A.1.b. of this document, suitable analytical
methodology is not available to identify and quantify all potentially
harmful impurities that may be present in lakes. Therefore, the agency
tentatively concludes that the premarket controls afforded by the
certification requirement are necessary to allow FDA to verify that the
conditions for safe use of lakes are being met. Therefore, the agency
is proposing to list lakes in part 74 as color additives subject to
certification.
Certification will allow the agency to confirm, before a lake is
marketed, that only safe and suitable components have been used to
prepare it; that any batches of straight color used in the lake were
previously certified; and that the straight-color component of the lake
has not degraded during manufacture or repacking. The agency
tentatively concludes, however, that not all aspects of the current
batch certification procedure are necessary to accomplish these
objectives, and is proposing a simplified procedure for certifying
batches of lakes. This proposed procedure is discussed in section VI.B.
of this document.
The agency is specifically requesting, as comments on this
proposal, comments on the usefulness of its proposed certification
procedure for the intended purpose of protecting the public health.
D. Provisions of Proposed Sec. 74.50 Lakes for Use in Foods
The agency is proposing new Sec. 74.50 to list lakes permanently
for use in foods as color additives subject to certification. Section
74.50(a)(1), (a)(2), and (a)(3) would designate the components
permitted for use in lakes for coloring food. These paragraphs would
authorize the use of certified batches of one or more of the straight
colors FD&C Blue No. 1, FD&C Blue No. 2, FD&C Green No. 3, FD&C Yellow
No. 5, FD&C Yellow No. 6, and FD&C Red No. 40; the substratum alumina
that either conforms to the requirements for alumina under
Sec. 73.1010(a)(1) and (b), or is a suspension in water of precipitated
aluminum hydroxide prepared from aluminum sulfate that meets the
requirements of the Food Chemicals Codex 2d ed. (1972) and sodium
carbonate or sodium hydroxide that meets the requirements of the Food
Chemicals Codex 3d ed. (1981); and precipitants that form the aluminum
cation (Al+3) and the anion chloride (Cl-1) or sulfate
(SO4-2).
Proposed Sec. 74.50(a)(4) would provide that only diluents that are
permitted in mixtures of straight colors for food use may be used in
color additive mixtures containing lakes for such use.
Proposed Sec. 74.50(b) would prescribe the following specifications
for lakes for food use: Lead (not more than 10 ppm), arsenic (not more
than 3 ppm), mercury (not more than 1 ppm). It would also state that
lakes shall be free from impurities other than those named in the
specifications, to the extent that such impurities may be avoided by
CGMP.
Proposed Sec. 74.50(c)(1) would permit the use of lakes in foods
generally, except in foods subject to a standard of identity that does
not authorize such use. The proviso relating to standardized foods
would clarify that authorization for use of lakes in this regulation
does not take precedence over any restrictions on color additive use in
a food standard regulation.
[[Page 8386]]
Currently, all the straight colors authorized for use in lakes for food
use are approved for the same food uses. Because this may not always be
the case, however, proposed Sec. 74.50(c)(2) would restrict the use of
a lake manufactured from more than one straight color to those uses
common to all of the straight colors in the lake.
Proposed Sec. 74.50(d) would identify each lake made as prescribed
in Sec. 74.50(a) as a listed color and would prescribe the formation of
its listed name from the names of the certified straight colors present
in the lake (in descending order of predominance), followed by the name
of the cation of the precipitant (aluminum) and followed by the words
``lake on alumina.'' The anion component of the precipitant would not
be included in the name of the lake because this anion is removed
during processing under conditions of CGMP and is not a component of
the final lake.
Proposed Sec. 74.50(e)(1) would require that the label of the lake
and of any mixtures prepared from it for coloring purposes conform to
the requirements of Sec. 70.25. Proposed Sec. 74.50(e)(2) would require
that the label of food products that contain a lake declare the
presence of the lake in accordance with Sec. 101.22(k) (21 CFR
101.22(k)). Proposed Sec. 74.50(e)(3) would require that butter,
cheese, and ice cream that contain a lake of FD&C Yellow No. 5 or FD&C
Yellow No. 6 be labeled in accordance with Sec. 101.22(k)(1). These
proposed labeling provisions are discussed more fully in sections
VI.C.2. and VI.C.3. of this document.
Proposed Sec. 74.50(f) would require that all batches of lakes be
certified in accordance with proposed regulations in part 80.
V. Safety Review and Proposed Actions for Lakes for Use in Drugs and
Cosmetics
A. Review of Components of Lakes for Use in Drugs and Cosmetics
The current provisional listing regulations for lakes for use in
drugs and cosmetics generally (Sec. 82.1051) and for use in external
drugs and cosmetics only (Sec. 82.2051) provide for use of the
following components: (1) The straight colors FD&C Blue No. 1
(Sec. 82.101), FD&C Blue No. 2 (Sec. 82.102), FD&C Green No. 3
(Sec. 82.203), FD&C Yellow No. 5 (Sec. 82.705), FD&C Yellow No. 6
(Sec. 82.706), D&C Blue No. 4 (Sec. 82.1104), D&C Green No. 5
(Sec. 82.1205), D&C Green No. 6 (Sec. 82.1206), D&C Orange No. 4
(Sec. 82.1254), D&C Orange No. 5 (Sec. 82.1255), D&C Orange No. 10
(Sec. 82.1260), D&C Orange No. 11 (Sec. 82.1261), FD&C Red No. 4
(Sec. 82.304), D&C Red No. 6 (Sec. 82.1306), D&C Red No. 7
(Sec. 82.1307), D&C Red No. 17 (Sec. 82.1317), D&C Red No. 21
(Sec. 82.1321), D&C Red No. 22 (Sec. 82.1322), D&C Red No. 27
(Sec. 82.1327), D&C Red No. 28 (Sec. 82.1328), D&C Red No. 30
(Sec. 82.1330), D&C Red No. 31 (Sec. 82.1331), D&C Red No. 33
(Sec. 82.1333), D&C Red No. 34 (Sec. 82.1334), D&C Red No. 36
(Sec. 82.1336), D&C Violet No. 2 (Sec. 82.1602), D&C Yellow No. 7
(Sec. 82.1707), D&C Yellow No. 8 (Sec. 82.1708), D&C Yellow No. 10
(Sec. 82.1710), and Ext. D&C Yellow No. 7 (Sec. 82.2707a); (2) the
substrata alumina, blanc fixe, gloss white, clay, titanium dioxide,
zinc oxide, talc, rosin, aluminum benzoate, and calcium carbonate; (3)
precipitants containing the cations sodium (Na+1), potassium
(K+1), aluminum (Al+3), barium (Ba+2), calcium
(Ca+2), strontium (Sr+2), and zirconium (Zr+4).
Additionally, the lakes of FD&C Red No. 40 prepared with the substrata
and precipitants listed above are permanently listed in Secs. 74.1340
and 74.2340.
The identity and specifications for the straight colors used to
prepare lakes are provided in the regulations cited above and generally
cross-reference the requirements of the permanent listing for the
straight color in part 74. As to substrata, Sec. 82.3 defines three of
the substrata used in lakes (alumina, blanc fixe, gloss white), but
provides no specifications for the materials to be used. Part 82 does
not identify or prescribe specifications for other substrata (clay,
titanium dioxide, zinc oxide, talc, rosin, aluminum benzoate, and
calcium carbonate) for lakes for drug or cosmetic use, or for the
precipitants to be used in the preparation of these lakes.
1. Straight Colors
a. Identity and uses. As discussed in sections III.C.1. and
III.C.6.a. of this document, the agency has tentatively concluded that
several of the straight colors currently listed for use in lakes for
coloring drugs and cosmetics either do not form lakes (D&C Red No. 17,
D&C Red No. 30, D&C Red No. 36, D&C Violet No. 2, and D&C Green No. 6)
or were not present in any batch of lake certified for drug or cosmetic
use before the enactment of the 1960 amendments (D&C Orange No. 11, D&C
Yellow No. 7, D&C Yellow No. 8, and D&C Green No. 5). The proposed
termination of the provisional listing of these straight colors for use
in lakes would mean that lakes of these straight colors would no longer
be permitted for coloring drugs and cosmetics. (See Table 1 in section
III.C. of this document for a summary of the current and proposed
regulatory status of straight colors addressed in this rulemaking.)
The agency has already reviewed the identity and safety of the
remaining straight colors currently permitted as components of lakes
for coloring drugs and cosmetics, either as part of its scientific
review of provisionally listed straight colors or in response to
petitions for the review of new color additives (Sec. 71.1). On the
basis of these reviews, the agency concluded that these straight colors
are safe for use in drugs and cosmetics and issued regulations in part
74 permanently listing them for such uses. The agency is proposing to
continue to permit the use of these straight colors as components of
lakes for use in drugs and cosmetics, subject to the exceptions and
proposed requirements discussed below.
In the Federal Register of September 30, 1975 (40 FR 44812), the
agency restricted the provisional listing of FD&C Blue No. 2 to uses in
foods and ingested drugs, the uses for which a petition had been filed
for the permanent listing of the color additive. In the Federal
Register of February 4, 1983 (48 FR 5252), the agency published a final
rule permanently listing FD&C Blue No. 2 for use in food (Sec. 74.102)
and ingested drugs (Sec. 74.1102). However, the provisional listing for
the lake of FD&C Blue No. 2 (Sec. 82.102) was not amended accordingly.
Therefore, despite the lack of a listing in part 74 authorizing the use
of FD&C Blue No. 2 in cosmetics, the provisional listing regulations
still permit the use of lakes of FD&C Blue No. 2 in cosmetics. Proposed
Sec. 74.2050 would correct this inconsistency by excluding FD&C Blue
No. 2 from the straight colors permitted as components of lakes for
cosmetic use.
The lakes of D&C Red No. 34 are provisionally listed in part 82 for
use in drugs and cosmetics without any restrictions. However, the
straight color is listed in part 74 for external drug and external
cosmetic uses only (Secs. 74.1334 and 74.2334), based on the agency's
safety evaluation of the straight color. The proposed permanent
listings for lakes for drug and cosmetic use (Secs. 74.1050 and
74.2050) would correct this inconsistency by limiting the use of a lake
to the use(s) permitted for the straight-color component(s) of the
lake. Thus, under the proposed regulations, any lake containing D&C Red
No. 34 would be allowed for use only in externally applied drugs and
externally applied cosmetics.
b. Use of previously certified batches. Currently, under
Secs. 82.1051 and 82.2051, manufacturers may use uncertified batches of
straight colors to
[[Page 8387]]
prepare most lakes for drug and cosmetic use. The resulting lake is
then subject to batch certification. The exceptions are the lakes of
D&C Red No. 33 (Sec. 82.1333), D&C Red No. 36 (Sec. 82.1336), and FD&C
Yellow No. 6 (Sec. 82.706), which must be prepared from previously
certified batches of the straight color. (As discussed in section
III.C.1. of this document, the agency is proposing to terminate the
listing of D&C Red No. 36 as a straight-color component of a lake for
drug or cosmetic use because it does not contain a salt-forming group.)
For the reasons discussed in section IV.A.1.b. of this document,
the agency tentatively concludes that the lack of adequate analytical
methods to determine levels of intermediates and other impurities in
lakes prepared from uncertified batches of straight colors precludes
the agency from prescribing conditions of safe use for lakes prepared
from uncertified batches of straight colors. Accordingly, the agency is
proposing to require that lakes for use in drugs and cosmetics,
including externally applied drugs and cosmetics, be prepared from
certified batches of straight colors.
As discussed above, under current regulations the lakes of many D&C
straight colors are prepared from uncertified batches of the straight
colors. However, lakes of D&C Red Nos. 6, 7, 31, and 34 are commonly
produced in situ (a process described in section I. of this document).
In FY-95 (Ref. 18), lakes of these straight colors represented about 55
percent of the total quantity of D&C lakes certified. The agency
recognizes that its proposal to require the use of certified batches of
straight color to prepare lakes for coloring drugs and cosmetics would,
in effect, prohibit use of the in situ process for preparing lakes.
However, as noted above, the reason for this proposed requirement is
that the safety of lakes prepared from uncertified batches of straight
color (including lakes prepared in situ) has not been demonstrated.
Specifically, the agency is not aware of the existence of any methods
that may be used to demonstrate that lakes produced by the in situ
process meet the specifications for impurities, including carcinogenic
constituents (e.g., para-toluidine in D&C Red Nos. 6 and 7), in the
listing regulation for the straight color. Because FDA has the
responsibility to ensure that color additives in foods, drugs, and
cosmetics are safe for their intended uses, the fact that no methods
that allow the safety of lakes produced in situ to be demonstrated
appear to be available leads the agency to propose that use of the in
situ method be discontinued. FDA recognizes, however, that the
potential costs associated with this proposed action may be
considerable, and therefore solicits proven methodology for analysis of
the lake for the impurities specified in the listing regulation for the
straight color. If such information is received in response to this
proposal, the need to prohibit the use of lakes prepared by the in situ
process will be obviated.
c. Stability. The straight colors that FDA proposes to permit as
components of lakes for drug or cosmetic use fall into the following
eight groups, based on chemical structure (Refs. 16 and 17):
Triphenylmethane (FD&C Blue No. 1, FD&C Green No. 3, D&C Blue No. 4);
pyrazolone (FD&C Yellow No. 5); monoazo (FD&C Red No. 4, FD&C Red No.
40, FD&C Yellow No. 6, D&C Orange No. 4, D&C Red No. 6, D&C Red No. 7,
D&C Red No. 31, D&C Red No. 33, and D&C Red No. 34); indigoid (FD&C
Blue No. 2); fluoran (D&C Orange No. 5, D&C Orange No. 10, D&C Red No.
21, and D&C Red No. 27); xanthene (D&C Red No. 22 and FD&C Red No. 28);
quinoline (D&C Yellow No. 10), and nitro (Ext. D&C Yellow No. 7). In
FY-95, D&C lakes accounted for approximately 20 percent of the total
poundage of lakes certified (Ref. 18). Of the D&C lakes certified in
FY-95, approximately 55 percent were lakes of the monoazo dyes
(primarily lakes of D&C Red Nos. 6 and 7), about 20 percent were lakes
of the fluoran and xanthene dyes (primarily lakes of D&C Red Nos. 21
and 27), and about 15 percent were lakes of quinoline dye (D&C Yellow
No. 10). No batches of lakes of the nitro dye (Ext. D&C Yellow No. 7)
were certified in FY-95.
Section IV.A.1.c. of this document sets forth the agency's
evaluation of data confirming the stability of certain straight colors
in the triphenylmethane, pyrazolone, monoazo and indigoid classes
during the laking process. This information includes data received from
CTFA in response to the 1979 NOI (Ref. 19), data generated by FDA (Ref.
21), and published studies (Refs. 17 and 22). In addition to these
data, the agency received a preliminary stability study for two
additional lakes prepared from monoazo dyes (FD&C Red No. 4 and D&C
Orange No. 4) (Ref. 26). The study, which was conducted by a color
additive manufacturer, compared the levels of total color, uncombined
intermediates, and subsidiary color in a certified batch of each
straight color to the levels of these materials in an aluminum lake
prepared from the batch. The study found no evidence that the straight
color degraded during manufacture of the lake.
Based on its evaluation of all these data, the agency tentatively
concludes that when prepared in accordance with CGMP,straight colors in
the monoazo, triphenylmethane, pyrazolone, and indigoid classes do not
degrade significantly during preparation of lakes for use in drugs or
cosmetics.
The agency received no studies evaluating the stability of the
straight colors in the fluoran, xanthene, quinoline, or nitro groups
during the laking process. However, the agency has reviewed
certification records for batches of lakes made from straight colors in
the fluoran, xanthene (Ref. 27), and quinoline (Ref. 28) classes. The
agency has not certified a batch of lake of Ext. D&C Yellow No. 7 since
1975; therefore, no recent certification data are available for lakes
of Ext. D&C Yellow No. 7.
The lakes of straight colors in the fluoran, xanthene, and
quinoline groups are not required to be prepared from certified batches
of straight color. Nevertheless, for lakes of the quinoline dye, D&C
Yellow No. 10, the agency determined that one manufacturer used
certified lots of D&C Yellow No. 10 to prepare the lake. The agency
evaluated certification reports for the 36 such batches of D&C Yellow
No. 10 lake that were certified in FY-95. The agency compared the
levels, adjusted for total color content of the lake, of one
intermediate (24 batches) and one subsidiary color (36 batches) in the
batches certified to the levels permitted for these impurities in the
straight color. The agency also determined total color accountability
for all 36 batches. As discussed in section IV.B.5. of this document,
the total color accountability was determined by comparing the actual
total color content of each batch of lake with the range of estimated
total color content for the same batch. The actual total color content
of the batch of lake was determined during certification of the batch.
The range of expected total color content of the lake was determined
from the amount (weight) of straight color in the batch, multiplied by
the range of expected total color content of the batch of straight
color (as a percentage), and divided by the weight of the batch of
lake. The lower limit of the range of expected total color content of
the straight color was the minimum total color permitted by the
applicable specification in the listing regulation for the straight
color. The upper limit of the range was assumed to be 100 percent.
All but one of the batches contained levels of the intermediate and
subsidiary color that, adjusted for total color content of the lake,
were within the limit set by the specification for the
[[Page 8388]]
straight color. These data show that it is technologically feasible to
prepare lakes of D&C Yellow No. 10 from certified batches of straight
color without significant increases in impurities derived from the
straight color. Over 40 percent of the batches had a total color
content within the theoretical range of expected color content. The
data showed that, after an adjustment for the total color content of
the lake, the levels of sulfonated quinaldines, which are presumptive
products of decomposition, remained within the specification limit for
the straight color. Therefore, the agency tentatively finds that the
data are adequate to conclude that there is no significant degradation
of D&C Yellow No. 10 during laking under conditions of CGMP.
The agency also evaluated FY-95 certification reports for lakes of
the fluoran and xanthene straight colors. These lakes were all prepared
from uncertified batches of straight color. To make its evaluation as
accurate as possible, the agency compared levels (adjusted for total
color content of the lake) of impurities found in the lakes to the
maximum levels permitted for the same impurities in certified batches
of straight color. The agency combined the data from the fluoran and
xanthene classes of lakes because, during the laking process, the
lactone group in the xanthene dyes is converted to the corresponding
salt. Therefore, lakes of straight colors from the xanthene class are
structurally identical to the lakes of comparable straight colors from
the fluoran class.
The agency evaluated the certification reports from the 104 batches
of lakes of the fluoran and xanthene straight colors that had been
certified in FY-95, including 16 reports for lakes of the xanthene
straight colors D&C Red No. 22 (3 batches) and D&C Red No. 28 (13
batches) and 88 reports for lakes of the fluoran straight colors D&C
Orange No. 5 (4 batches), D&C Red No. 21 (23 batches), and D&C Red No.
27 (61 batches). The agency compared the levels (adjusted for total
color content of the lake) of three intermediates (55 batches) and one
subsidiary color (104 batches) in these batches to the levels of these
impurities permitted by the specifications in the listing regulation
for the straight color. The agency also determined the total color
accountability for 104 batches. (The theoretical range of expected
total color content for these batches of lakes was determined in the
same manner as described above for batches of D&C Yellow No. 10 lakes.)
All but four of the batches contained levels of the intermediates and
subsidiary color that, after adjusting for the total color content of
the batch, met the specifications for the straight color. These data
show that it is technologically feasible to prepare lakes of the
fluoran and xanthene straight colors without significant degradation of
the straight color. Over 60 percent of the batches had a total color
content that was within the theoretical range of expected color
content. The analyses showed that, after adjustment for the total color
content of the lake, levels of the subsidiary colors
tribromofluoresceins (D&C Red Nos. 21 and 22) and the lower halogenated
fluoresceins (D&C Red Nos. 27 and 28), which are prime indicators of
possible dehalogenation (a decomposition reaction) of the parent
compound, remained within the applicable specifications for the
straight color. Therefore, the agency tentatively finds that the data
are adequate to conclude that no significant degradation of these
straight colors occurs during preparation of lakes under conditions
consistent with CGMP.
The agency tentatively concludes that the available information
provides sufficient evidence for the stability of the straight-color
component of lakes prepared from colors in the monoazo, pyrazolone,
triphenylmethane, indigoid, fluoran, xanthene, and quinoline classes.
Although the agency has not evaluated data for all of the straight
colors that FDA is proposing to approve as components of lakes for drug
and cosmetic use, the agency tentatively concludes that the available
information is adequate to conclude that there is no significant
degradation of straight colors in these classes during the preparation
of lakes in accordance with CGMP.
The agency has no data on the stability of the nitro straight
color, Ext. D&C Yellow No. 7, during the laking process. No lakes of
this straight color were certified in FY-95; the last batch of this
lake was certified by the agency in 1975. Based on the absence of data
concerning the stability of Ext. D&C Yellow No. 7 during the laking
process, the agency tentatively concludes that it has insufficient data
to ensure the safety of lakes prepared with Ext. D&C Yellow No. 7.
Therefore, the agency is not proposing to permit the use of Ext. D&C
Yellow No. 7 as a component of lakes for drug or cosmetic use.
Consequently, the proposed termination of the provisional listings of
lakes (see section VI.A.2. of this document) would remove the listing
for lakes of Ext. D&C Yellow No. 7. Anyone interested in the permanent
listing of lakes of Ext. D&C Yellow No. 7 should submit, as a comment
on this proposal, data showing the stability of Ext. D&C Yellow No. 7
during the laking process. If data on the stability of Ext. D&C Yellow
No. 7 lakes are received as a comment on this proposal, the agency will
consider permanently listing the lakes of Ext. D&C Yellow No. 7 in the
final rule.
The agency has also considered the safety evaluations for the
straight colors discussed above. Based on these safety evaluations and
the data showing the stability of straight colors when the laking
process is conducted in accordance with CGMP, the agency tentatively
concludes that, when lakes are prepared under conditions of CGMP, the
certified batches of straight colors listed in proposed Secs. 74.1051
and 74.2051 are safe for use in lakes for the same drug and cosmetic
uses as part 74 allows for the straight colors. Therefore, the agency
is proposing to permit certified batches of these straight colors as
components of lakes for drug or cosmetic use.
As discussed in section IV.A.1.c. of this document, the agency is
not proposing to establish a definition of CGMP for the preparation of
lakes. Rather, FDA is proposing to permit any manufacturing method that
ensures that straight colors do not significantly degrade during
laking.
d. Use of more than one straight color in a lake. For the reasons
discussed in section IV.A.1.d. of this document, the agency is also
proposing to permit the preparation of a lake from certified batches of
more than one straight color.
2. Substrata
a. Regulatory approach. The agency is proposing to include the
following in its permanent listing regulations for lakes for drug and
cosmetic use as substrata permitted for preparing such lakes: alumina,
barium sulfate, kaolin, titanium dioxide, zinc oxide, talc, aluminum
benzoate, calcium carbonate, and rosin. In addition, gloss white will
also be permitted, although not explicitly listed in the regulations,
because FDA is proposing to allow combinations of substrata. Thus, all
of the substrata currently permitted as components of lakes for drug
and cosmetic use under Secs. 82.1051 and 82.2051, the provisional
listing regulations, will continue to be permitted under the proposed
regulations.
Ordinarily, the agency establishes identity and specification
requirements for the color additive, rather than for the components
used to make the color additive. However, because of the unique
characteristics of lakes, the agency is proposing to regulate them
under a broadly based, flexible system that permits the use, in drug
and
[[Page 8389]]
cosmetic products, of lakes that may contain a variety of components at
varying levels. As noted above in section V.A.1.b. of this document,
the agency is proposing to establish quality requirements (identity and
specifications) for the straight-color components of lakes by requiring
the use of certified batches of straight colors to prepare lakes. To
ensure the safety of lakes prepared with the substrata listed above,
and at the same time to permit manufacturers the continued flexibility
to prepare lakes using any one or mixtures of these substrata at
varying levels, the agency is proposing to establish quality
requirements (identity and specifications) for these substrata or their
components. In this way, the agency can ensure the safety of substrata
used to prepare lakes without setting rigid specifications for the
finished lake to limit impurities in substrata, which may be present at
varying levels in a lake, and without requiring analysis of the lake
itself for these impurities.
b. Alumina. In section IV.A.2. of this document, the agency
reviewed the identity and safety of alumina, and tentatively concluded
that alumina is safe as a substratum in lakes for food use.
Furthermore, alumina is listed in Sec. 73.1010 as a color additive for
use in drugs generally at levels consistent with CGMP. Based on its
review of the use of alumina as a substratum in lakes for food use and
on the listing of alumina as a color additive safe for general use in
drugs, the agency tentatively concludes that alumina is also safe for
use as a substratum in lakes for drug and cosmetic use, provided that
it either conforms to the identity and specification requirements in
Sec. 73.1010 (a)(1) and (b), or is a suspension in water of
precipitated aluminum hydroxide prepared from aluminum sulfate and
sodium carbonate or sodium hydroxide that meet the requirements of Food
Chemicals Codex 2d ed. (1972) (aluminum sulfate) or Food Chemicals
Codex 3d ed. (1981) (sodium carbonate and sodium hydroxide).
c. Barium sulfate (blanc fixe). Section 82.3(h) defines blanc fixe
as ``a suspension in water of precipitated barium sulfate.'' The
definition provides no quality requirements for blanc fixe as a
substratum. This definition covers both preformed barium sulfate that
is subsequently suspended in water and barium sulfate that is prepared
in situ, without subsequent recovery and drying.
The United States Pharmacopeia 23d ed. (1990) (USP) defines barium
sulfate as ``BaSO4 233.39; sulfuric acid, barium salt (1:1);
Barium sulfate (1:1) [7727-43-7]'' and provides specifications. The act
recognizes the USP as an official drug compendium whose specifications
are applicable to drug uses of substances listed therein (21 U.S.C.
321(g)(1)(a) and 351(b)). Although the USP specifications for barium
sulfate and other compounds discussed below that are recognized by the
USP are not directly applicable for purposes of this proposal, the
agency tentatively concludes that the USP specifications for these
compounds when used as drugs are also appropriate for these compounds
when they are used as substrata for lakes to color drugs.
The agency has approved barium sulfate for use in adhesives
(Sec. 175.105) and as a colorant for food-contact use (Secs. 178.3297
(21 CFR 178.3297) and 176.170(b)(2)). As part of the current
rulemaking, the agency also evaluated data relating to the safety of
ingested and dermal uses of barium sulfate, and found no reports in the
scientific literature of adverse effects resulting from topical use of
barium sulfate. Moreover, scientific data establish that barium sulfate
is highly insoluble. For example, the CRC Handbook of Chemistry and
Physics (59th ed., 1978) reports that precipitated blanc fixe
(BaSO4) has a solubility in water of 0.246 milligram (mg)/100 gram
(g) at 26 deg.C and 0.4113 mg/100g at 100 deg.C and 60 mg/100g in 3
percent HCl. Consequently, its absorption and toxicity are low.
However, to provide further assurance of safety, the agency is
proposing to retain the current specification for soluble barium of not
more than 0.05 percent in lakes that contain a barium salt
(Sec. 82.5(b)(3)). The agency tentatively concludes that barium sulfate
that meets the requirements of the USP is safe for use as a substratum
in lakes for drug and cosmetic use (Ref. 13).
The definition in Sec. 82.3(h) for blanc fixe and the definition in
Sec. 82.3(i) for gloss white (a suspension in water of co-precipitated
aluminum hydroxide and barium sulfate) suggest that barium sulfate may
be prepared in situ either alone or with alumina during the manufacture
of lakes. The International Pharmacopoeia 3d ed. (1979) describes the
preparation of barium sulfate suspension by mixing barium chloride
solution, sulfate-free ethanol, and potassium sulfate solution. The
WHO's Specifications for Reagents Mentioned in the International
Pharmacopoeia (1963) describes barium chloride and potassium sulfate
and provides specifications for each. However, the agency has no
information to confirm that the International Pharmacopeia method and
the identity and specifications for barium chloride in the WHO
publication represent CGMP for preparing barium sulfate in situ as
substrata for lakes for drug or cosmetic use. Therefore, the agency
requests comments on appropriate methodology for the in situ
preparation of barium sulfate as a substratum, and on identity
requirements and specifications for reagents used to prepare this
substratum. If such comments are received and the information provided
is satisfactory, the agency will list barium sulfate prepared in situ
as a substratum in lakes for use in drugs and cosmetics.
The agency is also proposing to substitute the name ``barium
sulfate'' for ``blanc fixe.'' CTFA's comment on the 1979 NOI suggested
this change in terminology. The agency notes that, in the past, the
name ``blanc fixe'' was typically used to identify the substratum
composed of barium sulfate in requests for certification of lakes.
However, more recently, the name typically used for this substratum in
requests for certification is ``barium sulfate.'' Therefore, the agency
agrees with CTFA's comment and is proposing to substitute the name
``barium sulfate'' for the name ``blanc fixe.''
d. Gloss white. Section 82.3(i) defines gloss white as ``a
suspension in water of co-precipitated aluminum hydroxide and barium
sulfate''. As discussed above, the agency is proposing to permit both
alumina and barium sulfate as substrata in lakes for drug or cosmetic
use.
Therefore, the agency is proposing not to list gloss white as a
substratum in lakes for drug and cosmetic use, because the proposed
regulations provide for combinations of substrata.
e. Kaolin (clay). In the 1979 NOI, the agency stated that the term
``clay'' does not adequately identify the chemical structure of this
material. The NOI requested comments identifying the material and
suggesting specifications to ensure its safe use as a substratum in
lakes. CTFA's comment, submitted in response to the 1979 NOI,
identified kaolin as the substratum material used in lakes.
The USP (23d ed., 1995) defines kaolin as ``a native hydrated
aluminum silicate, powdered and freed from gritty particles by
elutriation,'' and provides specifications. The agency has affirmed
clay (kaolin) as GRAS in Sec. 186.1256 as an indirect food ingredient.
Section 186.1256 identifies clay (kaolin) as hydrated aluminum silicate
(Al2O3.2SiO2.nH2O) and provides a CAS Registry
number of 1332-58-7.
The agency has reviewed data relating to the safety of ingested and
dermal uses of kaolin and bentonite (a related
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mineral containing magnesium aluminum silicate). These data included
data developed for the GRAS review of these compounds and data in a
color additive master file, which included dermal toxicity data. The
agency also considered a 90-day feeding study on magnesium aluminum
silicate.
Based on its review, the agency finds that kaolin is inert when
applied externally and is not absorbed by the gastrointestinal tract. A
search of the scientific literature revealed no reports of adverse
effects resulting from topical use of kaolin. Therefore, the agency
tentatively concludes that kaolin that meets USP specifications is safe
for use as a substratum in lakes for drug and cosmetic use (Ref. 13).
f. Titanium dioxide. The color additive regulation for titanium
dioxide (Sec. 73.575) identifies titanium dioxide as ``synthetically
prepared TiO2'' and provides specifications. Titanium dioxide is
listed as a color additive exempt from certification for use in food
(Sec. 73.575), in drugs generally (Sec. 73.1575), in cosmetics
generally (Sec. 73.2575), and in certain medical devices
(Sec. 73.3126). The USP (23d ed., 1995) recognizes titanium dioxide,
defines it as ``TiO2 79.88; Titanium oxide (TiO2); Titanium
oxide (TiO2) [13463-67-7],'' and provides specifications.
The agency has evaluated the available data relating to the safety
of ingested and dermal uses of titanium dioxide, including data
supporting its use as a color additive, and more recent genetic and
chronic toxicity studies in rats and mice. Based on these data, the
agency tentatively concludes that titanium dioxide that meets the
requirements of Sec. 73.575 (a)(1) and (b) is safe for use as a
substratum in lakes for drug and cosmetic use (Ref. 13).
g. Zinc oxide. The color additive regulation for zinc oxide
(Sec. 73.1991) identifies zinc oxide as ``a white or yellow-white
amorphous powder manufactured by the French process (described as the
indirect process whereby zinc metal isolated from the zinc-containing
ore is vaporized and then oxidized).'' Section 73.1991(b) provides
specifications for zinc oxide. The USP (23d ed., 1995) recognizes zinc
oxide, defines it as ``ZnO 81.39; Zinc oxide; Zinc Oxide [1314-13-2],''
and provides specifications.
Zinc oxide is listed as a color additive exempt from certification
for use in externally applied drugs (Sec. 73.1991) and in cosmetics
generally (Sec. 73.2991). Zinc oxide is also GRAS for use as a dietary
supplement (Sec. 182.5991) and as a nutrient (Sec. 182.8991).
The agency has evaluated data relating to the safety of ingested
and dermal uses of zinc oxide, including a safety review of zinc
compounds as food ingredients by the Select Committee on GRAS
Substances of the Federation of American Societies for Experimental
Biology and the data supporting the safety of zinc oxide as a color
additive. Based on these data, the agency tentatively concludes that
zinc oxide that meets the requirements of Sec. 73.1991 (a)(1) and (b)
is safe for use as a substratum in lakes for drug and cosmetic use
(Ref. 13).
h. Talc. The color additive regulation for talc (Sec. 73.1550)
identifies talc as ``a finely powdered, native, hydrous magnesium
silicate sometimes containing a small proportion of aluminum silicate''
and provides specifications. Talc is a color additive exempt from
certification for use in coloring drugs generally (Sec. 73.1550) and is
GRAS for certain indirect food uses (Secs. 182.70 and 182.90). The USP
(23d ed., 1995) defines talc as ``a native, hydrous magnesium silicate,
sometimes containing a small proportion of aluminum silicate,'' and
provides specifications.
The agency has evaluated the available data relating to the safety
of ingested and dermal uses of talc, including a safety review of
silicates (including talc) as food ingredients by the Select Committee
on GRAS Substances of the Federation of American Societies for
Experimental Biology and the data supporting the safety of talc as a
color additive. Based on these data, the agency tentatively concludes
that talc that meets the requirements of Sec. 73.1550 (a)(1) and (b) is
safe for use as a substratum in lakes for drug and cosmetic use (Ref.
13).
i. Aluminum benzoate. During the preparation of a lake with
aluminum benzoate as a substratum, aluminum benzoate is produced in
situ using benzoic acid and the aluminum cation. The Merck Index (11th
ed., 1989) identifies aluminum benzoate as C21H15AlO6 or
Al(C6H5COO)3 with a molecular weight of 390.30. The USP
(23d ed., 1995) recognizes aluminum chloride, aluminum sulfate, and
benzoic acid (the components used to prepare aluminum benzoate). The
USP (23d ed., 1995) defines benzoic acid as ``C7H6O2
122.12; Benzoic acid; Benzoic acid [65-85-0]'' and provides
specifications. The U.S.P. (23d ed., 1995) defines aluminum chloride as
``AlCl3 6H2O; Aluminum chloride, hexahydrate; Aluminum
chloride hexahydrate [7784-13-6]; Anhydrous 133.34 [7446-70-0]'' and
provides specifications. The USP (23d ed., 1995) defines aluminum
sulfate as ``Al2(SO4)3 xH2O (anhydrous) 342.16;
Sulfuric acid, aluminum salt (3:2), hydrate; Aluminum sulfate (2:3)
hydrate [17927-65-0]; Anhydrous 342.16 [10043-01- 3]'' and provides
specifications.
The agency has affirmed benzoic acid (Sec. 184.1021) and sodium
benzoate (Sec. 184.1733) as GRAS for use in food as flavoring agents
and adjuvants and as antimicrobial agents. In addition, the standard of
identity for margarine (21 CFR 166.110) permits the use of the sodium,
potassium, and calcium salts of benzoic acid as preservatives. The
agency has also reviewed safety data on the ingested and dermal uses of
benzoic acid and benzoates, including a safety review of benzoic acid
and benzoates as food ingredients by the Select Committee on GRAS
Substances of the Federation of American Societies for Experimental
Biology and information identified in a search of the scientific
literature published from 1981 to 1987 on benzoic acid and benzoates.
The agency's review found no reports of adverse toxicological effects
of ingested or topically administered benzoic acid.
The agency's evaluation of the safety of aluminum salts, including
aluminum chloride and aluminum sulfate, is discussed in section IV.A.2.
of this document under the safety of alumina as a substratum in lakes
for food use.
Based on these data, the agency tentatively concludes that aluminum
benzoate prepared from benzoic acid and aluminum chloride or aluminum
sulfate that meet the USP specifications for these compounds is safe
for use as a substratum in lakes for drug and cosmetic use (Ref. 13).
j. Calcium carbonate. The color additive regulation for calcium
carbonate (Sec. 73.1070) identifies calcium carbonate as ``a fine,
white, synthetically prepared powder consisting essentially of
precipitated calcium carbonate (CaCO3).'' Calcium carbonate is
listed as a color additive exempt from certification for use in drugs
generally (Sec. 73.1070). Calcium carbonate has also been affirmed as
GRAS for general food use (Sec. 184.1191) and is GRAS for dietary
supplement use (Sec. 182.5191).
The agency has evaluated the available data relating to the safety
of ingested and dermal uses of calcium salts, including calcium
carbonate. These data, including a safety review of calcium salts as
food ingredients by the Select Committee on GRAS Substances of the
Federation of American Societies for Experimental Biology and data
supporting the safety of calcium carbonate as a color additive,
establish that calcium is ubiquitous in nature and
[[Page 8391]]
that its salts are commonly found in food. Based on its review, the
agency tentatively concludes that calcium carbonate that meets the
requirements of Sec. 73.1070 (a)(1) and (b) is safe for use as a
substratum in lakes for drug and cosmetic use (Ref. 13).
k. Rosin. ``Rosin'' is a generic term encompassing a variety of
substances that may vary considerably in their composition. For
example, the Merck Index (11th ed., 1989) defines rosin as ``Residue
left after distilling off the volatile oil from the oleoresin obtained
from'' various species of Pinus. Gum rosin is obtained from the
oleoresin of living pine trees and wood rosin is extracted from the
wood of the stumps of pine trees. Another type of rosin is tall oil
rosin, a by-product of the wood pulp industry. The CRC Handbook of
Chemical Synonyms and Trade Names (8th ed., 1978) also lists rosin
under its synonym 'colophony' and defines it as ``The residue which
remains after the volatile oils have been removed by the distillation
of crude turpentine.'' The CRC Handbook lists several varieties of
rosins obtained from different species of pine.
Rosin is approved as a food additive for use as a natural flavoring
substance for alcoholic beverages (Sec. 172.510). Various rosins and
rosin derivatives are approved for other food additive uses: In
coatings of fresh citrus fruits (Sec. 172.210) and as plasticizing
materials or softeners in chewing gum base (Sec. 172.615). Rosin and
rosin derivatives are approved as diluents in color additive mixtures
for use in inks for marking food supplements in tablet form, gum,
confectionery, fruit, and vegetables (Sec. 73.1(b)) and, by reference,
in inks for branding pharmaceutical forms (Sec. 73.1001(a)(2)).
Numerous rosins and rosin derivatives are approved as indirect food
additives (substances that are not added to food directly but that may
become part of food through migration from materials in contact with
the food) (Sec. 178.3870).
The agency has evaluated the available data relating to the safety
of rosin and related compounds, including data supporting the food
additive and color additive diluent uses of rosin and rosin
derivatives, and data obtained by the agency from searches of the
scientific literature in 1988 and 1994 for information concerning
rosin. The agency's literature searches did not find any reports of
adverse toxicological effects from ingested rosin. However, many
publications reported cases of allergic contact dermatitis and
occupational asthma resulting from exposure to certain rosin materials
(Ref. 13).
In the 1979 NOI, the agency requested information on the chemical
composition of rosin and suggestions for specifications to ensure its
safe use in lakes for drug and cosmetic use. CTFA's comment on the 1979
NOI provided general information on rosin, but did not identify the
specific types of rosin that are used as substrata in lakes. However,
the monograph for rosin in the CTFA International Cosmetic Ingredient
Dictionary, 5th ed., 1993 defines rosin as ``the residue left after
distilling off the volatile oil from the oleoresin obtained from Pinus
palustris and other species of Pinaceae (Ref. 29). Because this
definition clearly identifies gum rosin, and not wood rosin or tall oil
rosin, the agency tentatively concludes that the rosin used in cosmetic
products is gum rosin.
Based on its review of available data (Refs. 29 and 30), the agency
has tentatively identified the rosin used as a substratum in lakes for
drug and cosmetic use as gum rosin, and is proposing to define and set
specifications for rosin based on this tentative conclusion. It is
unclear, however, whether all lake manufacturers who use rosin as a
substratum are using gum rosin. Therefore, any manufacturer who uses
rosin other than gum rosin that meets the requirements in the proposed
regulation as a substratum in lakes for drug or cosmetic use should
submit information about the identity and specifications of such rosin
as a comment on this proposal. The comment should include the
manufacturer's product specifications and any analytical data that
establish the identity and purity of the rosin. The agency will
consider modifying the identity and specifications for rosin if it
receives information to substantiate the safe use of rosin other than
gum rosin.
In response to the concerns raised by the agency about the topical
safety of rosin lakes, the CTFA submitted reports of numerous human
sensitization and photosensitization studies on cosmetic products
colored with rosinated lakes of D&C Red No. 6, D&C Red No. 7, and D&C
Red No. 34. The studies involved a total of 2,381 subjects for
sensitization and 312 subjects for photosensitization; products tested
included lipsticks, lip liner, blush, rouge, and nail polish. No skin
sensitization/photoallergic reactions were reported in any of the test
subjects. The agency tentatively concludes that these studies show that
there is little risk of developing a skin sensitization reaction from
skin contact with various cosmetic products that contain rosinated
color additive lakes at levels found in such products, and, therefore,
that use of rosin as a substratum in color additive lakes for external
drug and cosmetic use is safe (Ref. 14).
3. Precipitants
a. Aluminum (Al+3), barium (Ba+2), and calcium
(Ca+2) cations. The safety of salts of the cations aluminum,
barium, and calcium is discussed in the safety evaluations of alumina
(sections IV.A.2. and V.A.2.b. of this document), barium sulfate (blanc
fixe) (section V.A.2.c. of this document), and calcium carbonate
(section V.A.2.j. of this document). Based on those evaluations, the
agency tentatively concludes that these cations are safe as components
of precipitants used in the preparation of lakes for drug and cosmetic
use (Ref. 13). However, as stated in the discussion of the safety of
barium sulfate as a substratum (section V.A.2.c.), the agency is
proposing to retain the current specification for soluble barium (0.05
percent) in lakes for drug or cosmetic use.
b. Zirconium cation (Zr+4). Zirconium is a rare earth metal
that closely resembles aluminum in pharmacological and chemical
properties. The agency has evaluated data relating to the safety of
ingested and dermal uses of zirconium salts. These data, including a
review of published literature on the toxicity, physiological effects,
and medicinal uses of zirconium and its salts, revealed nothing to
indicate any likelihood of harm from topical administration or
ingestion of low levels of zirconium salts (Ref. 13). Therefore, the
agency tentatively concludes that zirconium is safe as a component of
precipitants used in lakes for drug and cosmetic use.
c. Sodium (Na+) and potassium (K+) cations. The salts of
the sodium and potassium cations, sodium chloride and potassium
chloride, are ubiquitous in nature. Sodium chloride (table salt) is
GRAS (Sec. 182.1(a)) and potassium chloride has been affirmed as GRAS
for food use (Sec. 184.1622). Most of the permanently listed water-
soluble straight colors subject to certification, including all the
straight colors used as components of lakes under Sec. 82.51, are
sodium salts. By virtue of their GRAS status, sodium chloride and
potassium chloride are permitted under Sec. 73.1(a)(1) for use as
diluents in color additive mixtures for coloring food, and under
Sec. 73.1001(a)(1) and (b) are also permitted for use as diluents in
color additive mixtures for coloring ingested drugs and externally
applied drugs. Therefore, the agency tentatively concludes that these
salts are safe for
[[Page 8392]]
use as components of precipitants in lakes for drug or cosmetic use.
d. Strontium cation (Sr+2). Strontium is an alkaline earth
element and is a metabolic analog of calcium. The agency has evaluated
published data on the safety of strontium cation. Because strontium can
substitute for calcium, it can influence certain physiological
parameters; however, the concentrations required to adversely affect
these parameters are significantly higher than the levels encountered
when strontium is used as a precipitant in a lake. Based on its review
of the published data, the agency tentatively concludes that the use of
strontium cation is safe as a component of precipitants used in lakes
for drug and cosmetic use (Ref. 13).
e. Accompanying anions. In section IV.A.3.c. of this document, the
agency considered the safety of soluble chlorides and sulfates as
components of precipitants in lakes for food use. As discussed more
fully in that section, chloride and sulfate anions are found in many
GRAS ingredients. In the safety reviews conducted as part of the GRAS
rulemakings for these ingredients, the agency found that ingestion of
chlorides and sulfates (in the presence of the accompanying cation) was
safe at levels that vastly exceed the possible level of exposure to
these anions as components of lakes. Therefore, the agency tentatively
concludes that the presence of these anions in lakes prepared for food
use is safe (Ref. 13). Furthermore, by virtue of their GRAS status, the
salts of chloride and sulfate are permitted under Sec. 73.1(a)(1) for
use as diluents in color additive mixtures for coloring food, and under
Sec. 73.1001 (a)(1) and (b) are also permitted for use as diluents in
color additive mixtures for coloring ingested drugs and externally
applied drugs. Therefore, the agency tentatively concludes that these
anions are safe for use as components of precipitants in lakes for drug
or cosmetic use.
f. Tentative conclusions. The agency tentatively concludes that the
water-soluble chloride and sulfate salts of aluminum, barium, calcium,
zirconium, sodium, potassium, and strontium are safe for use as
components of precipitants in the preparation of lakes for drug or
cosmetic use. The agency notes that, although these substances are
discussed as distinct chemical compounds, the proposal would permit
their use in other forms to prepare lakes, provided that no substance
or ion that is not provided for in the regulation is introduced. For
example, the proposal would allow the use of a precipitant formed in
situ from the combination of a listed cation (as the hydroxide) and
either hydrochloric or sulfuric acid.
4. Diluents in Color Additive Mixtures Containing Lakes
The agency is not proposing any limitations on the diluents
permitted in color additive mixtures for cosmetic use that are made
with lakes. The part 74 listings for the straight colors that are
components of lakes for cosmetic use do not limit the use of diluents
in mixtures for coloring cosmetics. Moreover, no regulation in part 73
specifies safe diluents for cosmetic use. However, the agency notes
that cosmetic products containing color additive mixtures are subject
to the adulteration provisions of section 601 of the act.
B. Specifications for Lakes for Use in Drugs and Cosmetics
1. Intermediates and Other Impurities Derived from Straight Colors
The provisional listing regulations for lakes for drug or cosmetic
use (Secs. 82.1051 and 82.2051) contain specifications for ether
extracts (not more than 0.5 percent) and intermediates (not more than
0.2 percent) in such lakes. The agency established these specifications
to limit the levels of intermediates and other impurities in lakes
prepared from uncertified batches of straight colors. However, as
discussed in section IV.A.1.b. of this document, proven methodology to
analyze all lakes for intermediates and other impurities is not
available. Therefore, the agency is proposing to require the use of
certified batches of straight colors to ensure safe levels of
intermediates and other impurities in lakes. In light of this proposed
requirement, the agency tentatively concludes that specifications for
ether extracts, intermediates, and subsidiary colors in lakes for drug
or cosmetic use are unnecessary to ensure the safety of such lakes.
2. Precipitants
Because lakes are washed when prepared in accordance with CGMP, the
agency anticipates that only low levels of water-soluble contaminants
from these precipitants will remain in the finished lake. Furthermore,
the proposed specifications for the lake would limit the levels of
contaminants of toxicological concern (primarily heavy metals)
permitted in the end product. However, the agency tentatively concluded
in its discussion of barium sulfate as a substratum (section V.A.2.c.
of this document) and barium as a precipitant (section V.A.3.a. of this
document) that a specification to limit soluble barium in lakes for
drug or cosmetic use should be retained to provide an extra margin of
safety. Based on these considerations, the agency tentatively concludes
that specifications for residues from precipitants used in lakes for
drug or cosmetic use, except for soluble barium, are unnecessary.
3. Heavy Metals
As discussed in section IV.B.2. of this document, the manufacturing
processes for lakes involve reagents that are sources of potential
contamination by metals. Currently, lakes are subject to the following
general specifications in Sec. 82.5 for provisionally listed colors for
drug or cosmetic use: 20 ppm lead, 2 ppm arsenic, 0.003 percent total
heavy metals (except for lead and arsenic), and, for those colors that
contain a barium salt, a limit of 0.05 percent on soluble barium. As
discussed in section IV.B.2. of this document, FDA is proposing limits
for lead, arsenic, and mercury in lakes for food use. The agency
tentatively concludes that specifications to limit the levels of lead,
arsenic, mercury, and soluble barium are also necessary to ensure safe
use of lakes in drugs and cosmetics. The agency is unaware of any other
heavy metals that have a significant level of toxicity and that would
be expected to occur in lakes. Therefore, the agency tentatively
concludes that a general heavy metal specification is unnecessary to
ensure the safety of lakes for drug or cosmetic use.
The agency is proposing to maintain the specifications of not more
than 20 ppm lead and 0.05 percent soluble barium for lakes for drug or
cosmetic use and to raise the arsenic specification from not more than
2 ppm to not more than 3 ppm. The agency is also proposing to include a
mercury specification of not more than 1 ppm. The proposed levels for
arsenic and mercury are the levels that the agency tentatively
concludes are necessary to ensure the safety of color additives used in
drugs and cosmetics, based on safety evaluations in rulemakings for the
permanent listing of numerous straight colors.
4. Soluble Chlorides and Sulfates
Current Secs. 82.1051 and 82.2051 contain a specification that
limits the content of the soluble chloride and sulfate anions in lakes
for drug and cosmetic use. As noted in section IV.B.3. of this
document, most of the water-soluble chloride and sulfate anions are
washed out during preparation of the lake under CGMP conditions. In its
safety review, the agency found that these anions are safe in foods,
drugs, and cosmetics at levels considerably greater than those found in
lakes (Ref. 13). Therefore, the agency
[[Page 8393]]
tentatively concludes that a specification to limit the levels of
soluble chlorides and sulfates is unnecessary to ensure the safety of
lakes prepared in conformity with CGMP for drug or cosmetic use.
5. Other Residues
The 1979 NOI requested information on certain other chemicals
occasionally used in the laking process, such as citrate, acetate, and
surfactants. CTFA's comment did not provide a list of such substances,
but stated that the substances used were GRAS. A comment from a color
manufacturer identified specific substances that the company uses in
the manufacture of lakes and characterized them as food additives or
GRAS substances. The company stated that the surfactants were used at
very low concentrations and that the nature of the use prevented any
significant amount from being present in the final lake.
The agency recognizes that it is impracticable to set
specifications for every chemical used in the manufacture of a color
additive. The agency generally sets specifications to limit the
substances that are normally expected to be present in the final
additive, especially those substances that could present a safety
hazard at foreseeable levels of exposure. The agency agrees with the
comment that the surfactants and other chemicals mentioned are used at
low concentrations. The agency further agrees that, because of the
washing of lakes during manufacture, these chemicals are unlikely to be
present at significant levels in a lake that has been prepared under
conditions of CGMP and that is otherwise in compliance with applicable
regulations. Therefore, the agency is not proposing specifications for
residues of these substances in lakes for drug and cosmetic use.
6. Other Impurities and Contaminants
The agency has tentatively concluded above that specifications to
limit the levels of total heavy metals (except lead, arsenic, mercury,
and soluble barium), soluble chlorides and sulfates, and residues of
other chemicals are unnecessary to ensure the safety of lakes for drug
and cosmetic use, as long as a general provision is included in the
specifications for lakes to ensure that they are prepared in conformity
with CGMP. Therefore, the agency is proposing to continue the
requirement in existing Sec. 82.5 that lakes be free from all
impurities other than those named in the specifications, to the extent
that such impurities can be avoided by CGMP.
C. Certification Requirement
As discussed in section IV.C. of this document, the agency has
evaluated the necessity for the certification of lakes and has
tentatively concluded that certification is necessary to protect the
public health. The simplified procedure the agency is proposing for
certification of lakes is described in section VI.B. of this document.
D. Provisions of Proposed Regulations
1. Proposed Section 74.1050 Lakes for Use in Drugs
The agency is proposing a new Sec. 74.1050 to list lakes
permanently for use in drugs as color additives subject to
certification. Paragraphs (a)(1), (a)(2), and (a)(3) would designate
the components permitted for use in preparing lakes for coloring drugs.
These paragraphs would permit the use of one or more certified batches
of one or more of the color additives FD&C Blue No. 1, FD&C Blue No. 2,
FD&C Green No. 3, FD&C Yellow No. 5, FD&C Yellow No. 6, FD&C Red No. 4,
FD&C Red No. 40, D&C Blue No. 4, D&C Orange No. 4, D&C Orange No. 5,
D&C Orange No. 10, D&C Red No. 6, D&C Red No. 7, D&C Red No. 21, D&C
Red No. 22, D&C Red No. 27, D&C Red No. 28, D&C Red No. 31, D&C Red No.
33, D&C Red No. 34, and D&C Yellow No. 10 (see Table 1); one or more of
the substrata alumina, aluminum benzoate, barium sulfate, calcium
carbonate, kaolin, rosin, talc, titanium dioxide, and zinc oxide; and
one or more precipitants that form the cation aluminum (Al+3),
barium (Ba+2), calcium (Ca+2), potassium (K+), sodium
(Na+), strontium (Sr+2), or zirconium (Zr+4), and the
anion chloride (Cl-) or sulfate (So4-2). Paragraph (a)(3)
would require that the substrata (except alumina), or for aluminum
benzoate, the components of the substrata, conform to the identity and
purity requirements of the applicable color additive regulation or, if
no such regulation exists, to the requirements of the USP 23d ed.
(1995). The paragraph would require that alumina conform to the
requirements of Sec. 74.50(a)(3).
Proposed Sec. 74.1050(a)(4) would limit the diluents used in color
additive mixtures containing lakes to those diluents that are suitable
and that are listed in Sec. 73.1001 as diluents for drug use. This
requirement is consistent with the existing requirements for mixtures
of color additives for drug use and will ensure that color additive
mixtures containing lakes are safe for drug use. As discussed in
section III.C.2.b. of this document, the agency is proposing to amend
Sec. 73.1001 to permit additional diluents in color additive mixtures
for drug use.
Proposed Sec. 74.1050(b) would prescribe the following
specifications for lakes for drug use: lead (not more than 20 ppm);
arsenic (not more than 3 ppm); mercury (not more than 1 ppm); soluble
barium (not more than 0.05 percent). It would also state that such
lakes shall be free from impurities other than those named in the
specifications, to the extent that such impurities may be avoided by
CGMP.
Proposed Sec. 74.1050(c)(1) would restrict the use of a lake to
uses common to all of the straight colors in the lake. For example, use
of a lake of the straight colors FD&C Red No. 4 and FD&C Blue No. 1
would be limited to externally applied drugs and cosmetics because of
the limitations on the use of FD&C Red No. 4. Proposed
Sec. 74.1050(c)(2) would also specify that where regulations for the
straight color impose quantitative limitations for the use of such
straight color in drug products, the amount of such straight color in a
lake shall be considered as a part of the total amount of such straight
color permitted in a drug product.
Proposed Sec. 74.1050(d) would identify each lake made as
prescribed in Sec. 74.1050(a) as a listed color and would prescribe the
formation of its name from the names of the straight colors present in
the lake (in descending order of predominance), followed by the names
of the cations of the precipitants, and followed by the words ``Lake on
______ and ______'' (inserting the listed names of the substrata in
descending order of predominance). For example, the name of a lake
prepared by the extension of FD&C Yellow No. 5, FD&C Yellow No. 6 and
D&C Orange No. 5 on alumina using aluminum chloride as the precipitant
would be ``FD&C Yellow No. 5, FD&C Yellow No. 6 and D&C Orange No. 5
Aluminum Lake on Alumina''. The anion component of the precipitant
would not be included in the name of the lake because this anion is
removed during processing and is not a component of the finished lake.
Proposed Sec. 74.1050(e)(1) would require that the label of the
lake and of any mixtures prepared from it for coloring purposes conform
to the requirements of Sec. 70.25 of this chapter. Proposed
Sec. 74.1050(e)(2) would require that drug products that contain a lake
of FD&C Yellow No. 5 comply with the label declaration requirements of
Sec. 74.1705(c)(2) and (c)(3). Proposed Sec. 74.1050(e)(3) would
require that drug products that contain a lake of FD&C Yellow No. 6
comply with the label declaration requirements of proposed
Sec. 74.1706(c)(2). These proposed labeling
[[Page 8394]]
provisions are discussed more fully in sections VI.C.2. and VI.C.3. of
this document.
Proposed Sec. 74.1050(f) would require that all batches of lakes be
certified in accordance with proposed regulations in part 80.
2. Proposed Sec. 74.2050 Lakes for Use in Cosmetics
The agency is proposing new Sec. 74.2050 to list lakes permanently
for use in cosmetics as color additives subject to certification.
Proposed paragraph (a) would identify the components permitted for use
in preparing lakes for coloring cosmetics by incorporating the identity
provisions proposed in Sec. 74.1050(a)(1), (a)(2), and (a)(3) for lakes
for use in drugs, except that FD&C Blue No. 2 would not be permitted as
a straight-color component in lakes for cosmetic use. Proposed
Sec. 74.2050(a) also would incorporate the specifications in proposed
Sec. 74.1050(b).
Proposed Sec. 74.2050(b) would prescribe the same uses and
restrictions for lakes for cosmetic use as proposed for lakes for drug
use in Sec. 74.1050(c).
Proposed Sec. 74.2050(c) would identify each lake made as
prescribed in Sec. 74.2050(a) as a listed color and would prescribe the
formation of its name in the same manner as proposed in
Sec. 74.1050(d).
Proposed Sec. 74.2050(d)(1) would require that the label of the
lake and of any mixtures prepared from it for coloring purposes conform
to the requirements of Sec. 70.25. Proposed Sec. 74.2050(d)(2) would
require the ingredient labeling of lakes in cosmetic products to comply
with proposed Sec. 701.3(c)(1)(i). These proposed labeling provisions
are discussed more fully in sections VI.C.2. and VI.C.3. of this
document.
Proposed Sec. 74.2050(e) would require that all batches of lakes be
certified in accordance with proposed regulations in part 80.
VI. Other Proposed Actions
A. Removal of Provisional Listings
1. Removal of 21 CFR Part 81
The agency is proposing to remove Part 81 General Specifications
and General Restrictions for Provisional Color Additives for Use in
Foods, Drugs, and Cosmetics. This part was originally issued in 1960
(25 FR 9759, October 12, 1960) to provide for the listing of
commercially established color additives permitted for provisional use
under the transitional provisions of the 1960 amendments, and to
establish conditions for the continued provisional listing of these
color additives pending completion of studies required to establish
their safety for permanent listing.
Currently, only lakes are listed in Sec. 81.1 Provisional lists of
color additives. The final rule based on this proposal will remove
these entries. When the final rule becomes effective, the section will
no longer be necessary. The remaining three sections, Sec. 81.10
Termination of provisional listings of color additives; Sec. 81.30
Cancellation of certificates; and Sec. 81.32 Limitations of
certificates, concern past agency actions on provisionally listed color
additives and are purely of historical interest, as the color additives
referred to in these sections are no longer permitted for use in FDA-
regulated products. In addition, after FDA completes action on this
proposal and the final rule terminating all provisional color additive
listings becomes effective, no further additions to part 81 will be
possible. Therefore, the agency is proposing to remove the entire part.
2. Removal of 21 CFR Part 82
The agency is proposing to remove Part 82--Listing of Certified
Provisionally Listed Colors and Specifications. The purpose of this
part was to prescribe the identity, specifications, and uses of
provisionally listed color additives. Currently, the regulations in
this part apply only to lakes. When the final rule resulting from this
proposal becomes effective, all remaining provisional listings in part
82 will terminate. Therefore, the agency is proposing to remove the
entire part.
B. Certification Procedure for Lakes
1. Overview
The current requirements and procedures for batch certification of
lakes are described in part 80. Under the provisions of Sec. 80.21, a
firm that has prepared or repacked a batch of lake submits a request
for certification of the batch to FDA. The request provides the name,
batch number, and batch weight of the lake or repack; information on
storage pending certification; and the uses for which certification is
requested. For a newly manufactured batch of lake, the request also
provides the name, quantity, and (where applicable) the lot number of
the straight color used, the identity of the precipitant used, the
identity and quantity of the substratum used, and the identity (name
and address) of the manufacturer of the lake. For a repack of a
certified batch of lake, the request provides the original lot number,
certified color content, and name and address of the source from which
the repacker obtained the lake. (See section III.A.7. of this document
for the proposed definition of ``repack.'') The request must be
accompanied by the required certification fee, which varies according
to the type of request and weight of the batch (Sec. 80.10), and a
representative sample from the batch accompanied by any label or
labeling intended for use with the batch (Sec. 80.22).
The agency evaluates the request and analyzes the sample to ensure
that they meet the requirements of part 82, including identity,
specifications, and uses of the lake. After evaluation of the
information in the request and laboratory analysis of the sample, the
agency determines whether the request meets the requirements for
certification. For those requests that meet these requirements, the
agency issues the requester a certificate (Sec. 80.31). The certificate
states the name of the requester, the name of the color additive, the
FDA certification lot number, the uses and restrictions that apply to
the color additive, and the results of the agency's analyses of the
batch. Upon receipt of the certificate, the requester then labels the
batch with the certification lot number, the percent total color, uses
and restrictions, and other labeling as required in Sec. 70.25. The
requester is also required to maintain the batch, both before and after
certification, under conditions that ensure that the composition of the
batch does not change and that the sample submitted to FDA for
certification remains representative of the batch until the batch has
been packaged and labeled as required by Secs. 70.20 and 70.25
(Secs. 80.37 and 80.38). The person to whom the certificate is issued
is required to keep complete records showing the disposal of all color
additive from the batch covered by the certificate until at least 2
years after disposal of the batch (Sec. 80.39).
The requirement for certification of lakes and repacks ensures that
the agency can identify each firm that manufactures or repacks a lake.
Under its inspectional authority, the agency can then inspect these
establishments and determine compliance with labeling and storage
requirements and verify the disposal of the batch. The regulations
enable the agency to ensure the continued safety of lakes and other
color additives after certification by establishing conditions
(Sec. 80.32) under which a certificate will expire and the batch will
be deemed to be uncertified. In addition, the agency can refuse
certification service (Sec. 80.34) to firms that submit requests for
certification but fail to comply with requirements designed to ensure
the safety of certified
[[Page 8395]]
color additives, including recordkeeping and allowing inspection of the
firm's color additive inventory and records.
This batch certification procedure provides the agency with an
integrated system for ensuring the safety of lakes for use in foods,
drugs, and cosmetics. For each batch of lake certified, the agency
maintains, as records, the original request for certification and a
copy of the certificate for the batch, which includes the results of
agency analysis of the representative sample. The agency's analysis of
the representative sample includes tests for total color, heavy metals,
and impurities derived from the straight color used to prepare the
lake.
As discussed in section IV.C. of this document, the agency has
tentatively concluded that many requirements of the current batch
certification system are necessary to ensure that lakes are safe for
use in foods, drugs, and cosmetics, and thus to protect the public
health. However, the agency also tentatively concludes that FDA
analysis of a representative sample of the batch is not necessary in
light of the other requirements for lakes being proposed. Therefore,
the agency is proposing to establish a simplified procedure in
Sec. 80.31(b) for certification of batches of lakes and lake repacks.
The agency notes that both new batches of lakes and repacks of
previously certified batches of lakes would be subject to the new
procedure. In subsequent discussion of the proposed certification
requirements for lakes, the agency will address requirements for lakes
generically and will distinguish between new batches and repacks only
when it is necessary to identify specific requirements relating to only
one type of batch. In the remainder of this document, the term ``batch
of lake'' should be understood to encompass both new batches and
repacks.
Under the proposed procedure, certification of a batch of lake
would rely on the certificates for the batches of straight colors that
are used in the lake, either directly to prepare the lake or indirectly
as components of a certified batch of lake that is blended into the new
batch. The certification of the batch would also rely on
representations by the manufacturer or repacker that the batch complies
with the requirements of parts 74 and 80.
The proposed procedure would require that a batch of lake meet the
requirements of the proposed listing regulation for the lake in part
74, that the manufacturer of the lake be the same firm that was issued
the certificates for all batches of straight color in the batch of
lake, and that the firm complete the requirements of proposed
Sec. 80.33 for notifying the agency of the firm's claim to
certification for the batch. The proposed procedure would also require
that the firm submitting the notice maintain records of the composition
and disposal of the batch, including the certificates for the straight
colors used to make the batch. Repackers would be required to retain
proof that the original batch of lake was certified, in lieu of the
certificates for the batches of straight color used to prepare the
lake. The manufacturer or repacker would also be required to retain a
representative sample of the batch.
This proposed procedure would provide for routine agency review of
only the information necessary to ensure the use of certified batches
of straight color and to verify that the straight color in the lake did
not degrade significantly during the laking process. Under this
proposed procedure, the agency would not routinely monitor compliance
with the remaining requirements for the preparation and repacking of
lakes under the regulations in part 74. However, as noted above, the
certification of a batch of lake would be based both on the agency's
review of the critical factors in lake manufacturing and repacking and
on the manufacturer's and repacker's representations of compliance with
the remaining requirements. The agency would be able to verify these
representations by inspecting the manufacturer's or repacker's records,
and violations of the requirements for certification would be addressed
under proposed Secs. 80.32 and 80.34.
Under the proposed procedure, a manufacturer or repacker of a batch
of lake would submit to FDA a notice claiming certification for the
batch and providing the information and fee specified in proposed
Secs. 80.10(c) and 80.33. The notice would provide the same information
about the batch that is currently provided in a request for
certification under Sec. 80.21(j), or generated by the agency as part
of its evaluation of the certification request. However, the person
submitting the notice would not be required to submit a representative
sample of the batch for analysis by the agency. The agency would review
the notice and, if the information in the notice was complete and
appeared to comply with the requirements of parts 74 and 80, would
issue an acceptance of the notice. Upon FDA's issuance of its
acceptance of the notice, the batch covered by the notice would be a
certified batch.
As noted above, the proposed certification procedure for batches of
lakes and certified lake repacks would not require submission of a
representative sample for agency analysis. Instead, the proposed new
procedure would require that the manufacturer or repacker of the batch
provide certain analyses and maintain certain records for agency
inspection. Under the proposed procedure, the agency also would not
issue a certificate for the batch. As noted above, the proposed
certification procedure would rely on the certificates issued by the
agency for the straight-color components of batches of lake and the
representations of the manufacturer or repacker about the composition
of the batch. Under this proposed procedure, certification of a batch
of lake would be complete upon the agency's acceptance of the firm's
notice claiming certification. This notice would provide information
that would allow the agency to identify the certificates for the
straight colors on which the certification of the lake relies and to
ensure that the batch otherwise complies with the requirements of parts
74 and 80.
The agency is proposing to continue the application of the current
storage and labeling requirements for batches pending certification and
after certification (Secs. 80.37 and 80.38) to batches of lakes
certified under the proposed new procedure.
Amended Sec. 80.39 would continue the application of the current
recordkeeping requirements for certified color additives to lakes,
including repacks, and would add recordkeeping requirements for lakes
only to support the information and affirmations contained in the
firm's notice to FDA.
Amended Sec. 80.32 would provide for conditions under which the
certification of a batch of lake would expire, and would add a
provision to allow a certified color additive, including a lake, to be
used in a batch of lake without losing its certification.
Amended Sec. 80.34 would continue the agency's authority to refuse
certification service to manufacturers and repackers of lakes who
falsify records, obtain certification by fraud, or otherwise abuse the
certification system.
The proposed certification procedure would provide a simplified
system for assuring the safety of a certified batch of lake. For the
reasons discussed in section VI.B.2.b. of this document, preparation of
a lake would be limited to the firm issued the certificates for the
straight colors used in the batch of lake. For each certified batch of
lake, the agency would retain the original notice claiming
certification for the batch and a copy of its response to the notice.
The notice for each new certified batch of lake would contain the lot
numbers for
[[Page 8396]]
the batches of straight colors used to prepare the batch of lake. This
information would allow the agency to ensure that the batch of lake
meets the requirements in part 74. The proposed requirement for
submission of a premarket notice claiming certification would ensure
that the agency could identify every firm that prepares or repacks
certified batches of lakes. Under its inspectional authority, the
agency could then inspect these establishments and their records to
ensure compliance with the composition requirements of part 74 and the
certification requirements of part 80, including the recordkeeping
requirements of amended Sec. 80.39. As part of a typical inspection,
the agency might look at the facility, verify the records of the
disposal of the batch, and check compliance with storage and labeling
requirements.
The current batch certification procedure for lakes does not
provide for certification of mixtures containing lakes. Color additive
mixtures containing lakes are exempted from certification under
Sec. 80.35(b), subject to the conditions in that regulation. The agency
is proposing to retain this exemption.
2. Certification Requirements
a. Current provisions for batch certification. The current
requirements for batch certification of color additives in Sec. 80.31
include references to parts 81 and 82. As discussed in section VI.A. of
this document, the agency is proposing to delete parts 81 and 82 in
this rulemaking. Therefore, the agency is proposing to amend Sec. 80.31
to delete all references to parts 81 and 82.
Currently, Sec. 80.31(a)(2) requires that a certified color
additive conform to specifications and other conditions in parts 81 and
82. The section does not make any reference to specifications and other
conditions in part 74, however. Because it appears that this omission
was an oversight, the agency is proposing to amend Sec. 80.31(a)(2) to
add a reference to part 74. This action will clarify that permanently
listed straight colors are subject, as a condition of certification, to
the specifications and other conditions in part 74 of this chapter.
Currently, Sec. 80.31(b) specifies the conditions under which the
agency shall refuse to certify a batch and the procedures for
contesting such refusal. The agency is proposing to modify this
paragraph to cover the proposed changes in the procedure for
certification of lakes. The agency is also proposing to redesignate
this paragraph as paragraph (c) to allow the addition of the proposed
new procedure in new paragraph (b).
b. Proposed certification provisions for lakes. The agency is
proposing to add new Sec. 80.31(b) to specify the conditions under
which a batch of lake or certified lake repack is a certified batch.
Proposed Sec. 80.31(b) would require that a certified batch of lake or
certified lake repack meet the specifications and any other conditions
set forth in part 74 of this chapter. The agency tentatively concludes
that this is an essential condition for certification because proposed
Secs. 74.50, 74.1050, and 74.2050 specify the conditions under which
lakes are safe for use in foods, drugs, and cosmetics.
Proposed Sec. 80.31(b) would also require, as a condition of
certification for a batch of lake, that the firm preparing the batch be
the same firm that was issued the certificate for each batch of
straight color used in the lake. The agency tentatively concludes that
this provision is a necessary condition for certification because,
under the proposed procedure, certification of a batch of lake relies
on the certificates issued for the batches of straight colors that were
used to prepare the lake.
Under the proposed procedure, the agency would not issue a separate
certificate for the batch of lake. Instead, the certificates for the
straight colors in the lake would remain in effect provided that the
lake was prepared in accordance with the regulations in part 74,
including the requirement of preparation under conditions of CGMP such
that the straight color does not significantly degrade. The agency
recognizes that during the preparation of a lake, some change in the
composition of the straight color inevitably occurs because the color
goes from a water-soluble form in the straight color to a water-
insoluble form in the lake. However, it is the responsibility of the
manufacturer of the lake to prevent avoidable changes in the
composition of the straight color so that the certificates for all
straight colors used in the lake remain valid. The agency tentatively
concludes that the responsibility for assuring the validity of the
certificates of the straight colors in a lake should be retained by the
firm issued the certificates.
The agency notes that a repacker of a certified lake would not be
the same firm that was issued the certificates for the straight-color
components of the lake. However, the handling of a lake during
repacking is significantly less than during the preparation of the lake
because no reprocessing occurs and no chemical reaction takes place;
thus, the potential for change in composition is much less.
Furthermore, a repack is derived from a single batch of lake, and the
agency would keep on file all notices claiming certification for a
batch of lake under Sec. 80.31(b) and all agency acceptances of such
notices. Therefore, the agency would have the necessary information on
the certification of the original batch of lake to compare to the
information submitted in a notice claiming certification for a repack
of the batch.
Proposed Sec. 80.31(b) would require that a firm that prepares or
repacks a batch of lake comply with the notification requirements of
Sec. 80.33 as a condition of certification. Proposed Sec. 80.33 would
require that the firm submit and obtain FDA acceptance of a notice
claiming certification of the batch. The proposed notice would provide
FDA with the same information, except for the representative sample of
the batch, that is currently provided by the request for certification
of a batch of lake or generated by the agency when it analyzes the
sample and evaluates the request for certification.
Proposed Sec. 80.31(b) would also require that a firm that prepares
or repacks a batch of lake comply with the recordkeeping requirements
of Sec. 80.39 as a condition of certification. Currently, Sec. 80.39
requires that the person issued a certificate for a batch of color
additive maintain records showing the disposal of all the color
additive from the batch covered by the certificate. This section also
specifies the types of records required to be kept and the required
length of time for keeping the records, as well as requiring that such
records be made available to agency representatives. This section
further provides the agency access to check the correctness of the
records. The agency is proposing to maintain the current recordkeeping
requirements for lakes. The agency is also proposing to amend
Sec. 80.39 to require additional records that would apply to lakes
only. These additional records would allow the agency to verify the
information provided in the notice claiming certification. The proposed
new recordkeeping requirements are essential to the success of the
simplified certification procedure for lakes, as they would provide the
means for the agency to verify that a batch of lake has been prepared,
repacked, and maintained in compliance with safety requirements, and to
trace any batches that are found to have problems.
The agency would review the notice claiming certification and, if
the batch of lake covered by the notice appeared to comply with these
requirements and the notice appeared to contain no
[[Page 8397]]
untrue statement of a material fact, would issue an acceptance of the
notice. Upon issuance of the acceptance, the batch covered by the
notice, subject to the terms, conditions and restrictions prescribed in
part 74, would be a certified batch.
3. Notification Requirements
a. General requirements. An essential component of the agency's
proposed certification procedure for lakes is the proposed requirement
that a firm claiming certification for a batch of lake comply with the
notification requirements in Sec. 80.33. The proposed notice would be
the primary vehicle for providing the agency with the information
needed to verify that the batch is safe for use in foods, drugs, and
cosmetics.
Proposed Sec. 80.33 (a), (b), (c), and (d) would require that a
notice claiming certification for a batch of lake be addressed to the
Commissioner of Food and Drugs, be prepared in the format specified in
Sec. 80.33(i), be submitted in duplicate, and be signed by a
responsible officer of the company (or, for a foreign manufacturer or
repacker, by a responsible officer of the firm and by an agent of the
firm who resides in the United States). Except for the format of the
notice, these requirements are identical to the requirements for a
request for certification of a batch of lake or repack under
Sec. 80.21.
Proposed Sec. 80.33(e) would require that a notice claiming
certification for a batch of lake show the name and address of the firm
submitting the notice. This information is needed to issue a response
to the notice and also to identify the location of the batch and the
records supporting the notice.
Like existing Sec. 80.21(f), proposed Sec. 80.33(f) would require
that the notice be accompanied by the fee prescribed in Sec. 80.10
unless the firm has advanced a deposit to be used for prepayment of
such fees. Currently, the fee for certification of lakes and lake
repacks is based on the poundage of the color additive, with a minimum
fee of $192.00 for a batch of lake and $30.00 for a repack. Under
proposed Sec. 80.10(c), the fee for a notice claiming certification for
a batch of lake or lake repack would be $30.00 regardless of the size
of the batch. This proposed fee is based on the agency's estimate that
reviewing and responding to a notice claiming certification would
require approximately 1 hour. The agency estimates that average total
personnel costs for these activities would be approximately $25.00 per
notice with an additional $5.00 per notice for recordkeeping and other
overhead costs. The agency is proposing a flat fee rather than a fee
based on the poundage of lake certified because the manufacturer of a
lake has already paid a fee based on poundage for the certification of
the straight colors used in the lake. The agency estimates that the
resources required for the administrative handling, review, and
response to a notice claiming certification for a new batch of lake or
a lake repack would be essentially the same. Therefore, the agency is
proposing the same fee for both types of notices.
Proposed Sec. 80.33(g) would require that a copy of the label or
labeling intended to be used with the batch accompany the notice. This
proposed requirement is comparable to the current requirement
(Sec. 80.22(c)(5)) that the sample submitted with the request for
certification be accompanied by a copy of the label or labeling
intended to be used with the batch. The agency notes, however, that
under proposed Sec. 80.33, no sample would be submitted with the
notice.
Proposed Sec. 80.33(h) would state that the name of the lake is
derived as prescribed in part 74. This proposed provision is comparable
to Sec. 80.21(h), which cross-references the regulations that prescribe
the naming of straight colors, mixtures, and repacks.
Under proposed Sec. 80.33(j), the agency would respond to the
notice claiming certification for a batch of lake within 5 working days
of receipt. The agency's response would either accept or reject the
notice, as discussed in section VI.B.3.d. of this document.
b. Requirements for new batches of lakes. Proposed Sec. 80.33(i)(1)
would prescribe the format and content of a notice claiming
certification for a newly prepared batch of lake. The notice would be
required to contain the name of the lake, as prescribed in Secs. 74.50,
74.1050, or 74.2050; the batch number (manufacturer's number); the
weight of the batch; conditions of storage pending certification; and
proposed uses. This information is comparable to that currently
required for an application for certification of a lake under
Sec. 80.21(j)(2).
Proposed Sec. 80.33(i)(1) would also require that the notice state
the total color content of the batch and the color content (as a
percent of the batch) for each straight-color component of the lake.
The total color content of a lake is essential to the identity of the
lake, and necessary for the user of a lake to determine product
formulation requirements and to ensure compliance with any quantitative
limitations on the use of the straight-color component of a lake.
Currently, in its routine certification analysis of the representative
sample, the agency determines the total color content of a lake. This
information is an essential part of the basis for the certificate
issued by the agency. Under the proposed simplified certification
procedure for lakes, the agency would not analyze a sample of the batch
and determine the total color content. Rather, the manufacturer would
provide this information in the notice, based on its analysis of the
lake. These analyses would be part of the records that the manufacturer
would be required to maintain for the batch of lake.
Proposed Sec. 80.33(i)(1) would also require the notice to contain
the following information for the components of the lake: the name,
quantity used, and certification lot number of each batch of straight
color used in the preparation of the lake; the name and quantity used
of each precipitant or substratum ingredient in the lake, including the
source of the chloride or sulfate anion; and, for each certified batch
of lake blended into the batch, the name, quantity used, and
certification lot number or FDA acceptance number (the number assigned
to FDA's acceptance of the notice claiming certification). This
information is comparable to that currently required for an application
for certification of a lake under Sec. 80.21(j)(2). Although
Sec. 80.21(j)(2) does not currently require information on certified
batches of lakes that are blended into a new batch of lake, such
information is important for describing the composition of a batch of
lake and reflects a practice that is common in the industry. Such
information is routinely included in current requests for certification
of lakes under Sec. 80.21.
In evaluating requests it has received for certification of batches
of lakes, the agency has noted that, although the regulations for lakes
in part 82 specify precipitants and substrata as distinct functional
entities, the functions of ingredients that are added to the lake
preparation for these purposes may overlap. Also, in some instances,
acid is added to make a component water-soluble so that it can function
as a precipitant in the laking process. Under proposed
Sec. 80.33(i)(1), the required information on ingredients of the lake
in the notice claiming certification would encompass all ingredients
that are either identified in Secs. 74.50(a), 74.1050(a), or 74.2050(a)
as components of lakes, or are added to form these components of lakes
in situ. This information, together with the name of the lake, would
provide the agency with the necessary information on the components of
the lake and the ingredients used to form
[[Page 8398]]
these components in the preparation of the lake.
Proposed Sec. 80.33(i)(1) would also require statements affirming
that the batch meets the requirements of 21 CFR parts 74 and 80; that
the records required by Sec. 80.39, including a representative sample
of the batch, are available for inspection by FDA; and that the firm
submitting the notice is the manufacturer of the batch. These proposed
affirmations are necessary to ensure that the batch of lake meets all
the requirements of proposed Sec. 80.31(b) and, therefore, that the
batch is safe for use in foods, drugs, or cosmetics.
As discussed in section VI.B.1. of this document, the agency is
proposing to provide for the certification of batches of lakes based on
its review of the critical factors in lake manufacture and on the
manufacturer's representations that the remaining requirements have
been met. Under this proposed procedure, the agency would not routinely
verify compliance with every requirement for the preparation and
repacking of lakes in part 74; therefore, affirmations of compliance
with these requirements from the manufacturer of each batch are
necessary as a condition of certification.
c. Requirements for repacks of certified lakes. Proposed
Sec. 80.33(i)(2) would prescribe the format and content of a notice
claiming certification for a repack of a previously certified batch of
lake. The notice would be required to contain the name of the lake, as
prescribed in proposed Secs. 74.50, 74.1050, or 74.2050, and the
following information for the original certified batch of lake that was
repacked: FDA acceptance number for the manufacturer's notice claiming
certification (or the certification lot number, if the batch was
certified under the old procedure); total color content of the batch;
color content for each straight color in the batch; and the
manufacturer's name and place of business. Proposed Sec. 80.33(i)(2)
would also require the following information about the repacked batch
of lake: The batch number, weight of batch, total color content, and
the color content of each straight color in the batch, as well as
conditions of storage pending certification and proposed uses. This
information is comparable to that currently required for an application
for certification of a repack under Sec. 80.21(j)(3).
Proposed Sec. 80.33(i)(2) would also require statements affirming
that the batch meets the requirements of 21 CFR parts 74 and 80; that
the records required by Sec. 80.39, including a representative sample
of the batch, are available for inspection by FDA; and that the firm
submitting the notice is the repacker of the batch.
d. Agency action on the notice. Under proposed Sec. 80.33(j), the
agency would furnish a response to each notifier within 5 working days
of receipt of the notice. The agency would review the notice and, if
the information in the notice was complete and appeared to comply with
the requirements of parts 74 and 80, would issue an acceptance of the
notice. Upon issuance of the acceptance, the batch would be a certified
batch. To facilitate identification of the batch, the acceptance
document would be assigned a number.
If the information in the notice claiming certification was
incomplete or did not appear to comply with the requirements of parts
74 and 80, the agency would issue a rejection of the notice. Proposed
Sec. 80.33(j)(2) would state that a batch of lake covered by a rejected
notice has not complied with the requirements of Sec. 80.31(b) and is
not a certified batch. The proposed procedure would not provide for
interim responses by the agency or for amendment of a notice by the
submitter. The agency recognizes that a rejection of a notice may
result from an oversight on the part of the submitter, such as the
inadvertent omission of required information. If the deficiency in the
notice was such that it could be corrected, the firm could submit a new
notice that contained all the required information or otherwise
corrected the deficiency. However, the resubmission would be considered
a new notice. In addition, under proposed Sec. 80.31(c), the notifier
would also have the option to request a hearing on the rejection.
4. Recordkeeping Requirements
The current recordkeeping requirements for certified color
additives are found in Sec. 80.39 Records of distribution. This section
requires that the person to whom a certificate is issued keep complete
records showing the disposal of all the color additive from the batch
covered by such certificate. The section also specifies the length of
time the records must be kept (2 years after disposal of the batch) and
permits FDA access to the facility to check the accuracy of these
records. It also specifies that these records must be kept separately
from all other records. The agency is proposing to maintain these
recordkeeping requirements for certified batches of lakes by modifying
the language of Sec. 80.39 to conform to the proposed changes in the
certification procedure for lakes.
The agency is also proposing to require in Sec. 80.39(b) that a
firm submitting a notice claiming certification for a batch of lake
keep additional records that confirm the information submitted in the
notice. Under proposed Sec. 80.39(b)(1), a manufacturer or repacker of
a batch of lake certified under Sec. 80.31(b) would be required to
retain records of all documents that the firm relied upon to establish
the certified status of the batch of lake. For the manufacturer of a
lake, such documents would include copies of the notice submitted to
FDA claiming certification for the batch of lake, the FDA acceptance of
the notice, the certificate for each batch of straight color used to
prepare the batch of lake, the FDA acceptance (or, for batches
certified before the effective date of this final rule, the
certificate) for each batch of lake used as an ingredient in the batch
of lake, and the manufacturer's specifications for the substrata used
to prepare the batch of lake. For the repacker of a lake, such
documents would include copies of the notice submitted to FDA claiming
certification for the batch of lake, and the FDA acceptance of the
notice.
These records would also include complete reports of any chemical
analyses performed on the batch or its components, including records of
analyses that show the total color content of the batch as a percentage
and, if the batch contains more than one straight color, the color
content of each straight-color component of the batch of lake. As noted
above in section VI.B.3.b. of this document, an accurate statement of
total color content is essential for identification and proper use of a
lake. Complete records of the analyses would include a method
description in sufficient detail to allow the analysis to be repeated,
the experimental data, the final results and a clear description or
calculations that show how the final results were obtained from the
experimental data. The agency tentatively concludes that complete
records of the analyses for total color in a batch of lake are
necessary to allow the agency to verify the accuracy of the identity of
the lake.
For new batches of lakes, proposed Sec. 80.39 would require that,
for each batch of lake that contains a barium salt, as permitted under
Secs. 74.1050 and 74.2050, the manufacturer maintain complete records
of the analyses that show that the batch of lake conforms to the
specification for soluble barium. Barium is a heavy metal whose safety
in lakes is based on its insolubility (see section V.A.2.c. of this
document). In lakes containing barium salts, soluble
[[Page 8399]]
barium is either deliberately introduced as a precipitant, or could
form under the conditions of laking. Therefore, the agency tentatively
concludes that analysis of the batch for soluble barium is necessary to
ensure the safety of lakes that contain barium salts.
For new batches of lakes, the agency is proposing that the records
for the batch would also include the manufacturer's specifications for
substratum and precipitant ingredients used in the lake, as well as a
copy of the certificate for each batch of straight color used to
prepare the lake and a copy of the acceptance of the notice claiming
certification (or the certificate, during the transition between the
old and new procedures) for each batch of lake that was used as an
ingredient in the lake. These additional records would allow the agency
to verify the information and the affirmations about the identity and
composition of the lake in the notice claiming certification.
Under proposed Sec. 80.39(b)(2), the manufacturer or repacker of a
batch of lake certified under proposed Sec. 80.31(b) would be required
to retain an 8-ounce sample of the batch. The requirements for taking,
storing, and labeling this sample are provided in proposed
Sec. 80.22(b). The requirements are similar to those in existing
Sec. 80.22 for samples to accompany a request for certification.
However, proposed Sec. 80.22(b) also specifies when the sample is to be
taken; storage conditions for the sample; and additional labeling to
show the total color, the date the sample was taken, and (following FDA
acceptance of the notice claiming certification) the FDA acceptance
number.
The agency is proposing that the timeframes and conditions for
agency access to these additional records, including the sample of the
batch retained by the firm, be the same as currently specified in
Sec. 80.39 for records of distribution for certified color additives.
5. Treatment of Batches of Lakes Pending Certification and After
Certification
Current Sec. 80.37 Treatment of batch pending certification and
Sec. 80.38 Treatment of batch after certification contain requirements
to ensure that the composition of a batch of color additive subject to
certification does not change from the composition of the
representative sample of the batch that was submitted to the agency and
that formed the basis for the agency's issuance of the certificate for
the batch; that the batch remains under control of the person
requesting certification until it has been certified; and that the
batch is clearly identified as the batch for which certification was
requested or obtained. The proposed revision of these sections would
maintain these requirements or comparable requirements for batches of
lakes to be certified under Sec. 80.31(b).
a. Treatment of batches of lakes pending certification. Section
80.37 specifies the storage and labeling requirements for a batch of
color additive pending certification. The requirements of this section
are triggered by the act of taking a representative sample from the
batch of color additive for submission to FDA with the request for
certification, and they continue until the requested certificate has
been issued. The agency is proposing to amend Sec. 80.37 to continue
the requirements and conditions of this section for lakes subject to
certification under proposed Sec. 80.31(b). Specifically, the agency is
proposing to amend the description of the sample in Sec. 80.37 to
include a sample taken and held as a record by the manufacturer or
repacker of a batch of lake certifiable under proposed Sec. 80.31(b).
The agency is also proposing to amend Sec. 80.37(b) to specify that the
batch must be held under the control of the person requesting or
claiming certification until certified. Finally, the agency is
proposing to amend Sec. 80.37(c) to specify that the batch must be
marked in a manner such that there can be no question that the batch
may not be used until the issuance of the certificate for the batch or,
for lakes, the issuance of FDA's acceptance of the required notice
claiming certification.
b. Treatment of batches after certification. Section 80.38
specifies the storage, labeling and use requirements, and limitations
that apply to a batch of color additive after certification. The agency
is proposing to amend Sec. 80.38 to continue the requirements and
conditions of this section for lakes under the proposed certification
procedures in Sec. 80.31(b). Specifically, the agency is proposing to
amend Sec. 80.38 to divide it into two subsections: (a) Labeling and
(b) Storage. The agency is also proposing to establish two
subparagraphs under Sec. 80.38(a) to describe the labeling requirements
for batches of color additives certified under Sec. 80.31(a) and
Sec. 80.31(b), respectively. In both cases, the trigger for labeling
would be notification from FDA that the batch is a certified batch.
However, a batch certified under proposed Sec. 80.31(b) would be
identified by labeling it with the FDA acceptance number, rather than
with the certified lot number. The agency is also proposing to amend
Sec. 80.38(b) to clarify that the person responsible for the storage
and use of the batch after certification is the person requesting or
claiming certification.
6. Color Additive Mixtures
Current Sec. 80.35 refers to ``straight colors'' in describing the
ingredients in color additive mixtures to be certified (Sec. 80.35(a))
and in color additive mixtures exempt from certification
(Sec. 80.35(b)). Currently, the term ``straight color'' is defined to
include lakes. As noted in section III.A.1. of this document, the
agency is proposing to amend the definition of ``straight color'' to
exclude lakes and to define a new term ``listed color'' that would
include both straight colors and lakes. Therefore, the agency is
proposing a conforming amendment to substitute the term ``listed
color'' or ``listed colors'' for the term ``straight color'' or
``straight colors'' in Sec. 80.35.
7. Enforcement Provisions
a. Limitations of certification. Current Sec. 80.32 specifies
conditions under which the certificate for a batch of color additive
expires. The agency is proposing to adapt the provisions of Sec. 80.32
to the proposed new procedure for certification of lakes.
As explained in section VI.B.1. of this document, under the
proposed new certification procedure for lakes, the agency would not
issue a certificate for a batch of lake. Instead, the certification of
a batch of lake would rely on the certification of the straight colors
used in the batch of lake, on the affirmations in the notice claiming
certification, and on agency acceptance of the notice. The
certification of a repacked batch of lake would rely on the
certification of the original batch of lake rather than directly on the
certification of the straightcolor components of the lake. The agency
is proposing to amend Sec. 80.32 to clarify that the certification of a
batch of lake is inextricably linked to the certificates for the
straight colors used to prepare the lake. As proposed, the expiration
of the certificate for a batch of straight color would result in the
expiration of the agency's acceptance of all notices claiming
certification of batches of lakes made from that batch of straight
color, including any repacks of such batches.
The agency is proposing to change the title of Sec. 80.32 from
``Limitations of Certificates'' to ``Limitations of Certification'' to
expand the application of Sec. 80.32 to the proposed certification
procedure for lakes, which would not result in the issuance of a
certificate by the agency.
[[Page 8400]]
Current Sec. 80.32(a) provides that a certificate that is obtained
through fraud or misrepresentation of a material fact shall not be
effective, and that any color additive from the batch covered by the
fraudulently obtained certificate shall be considered to be from an
uncertified batch. Proposed Sec. 80.32(a) would continue the
applicability of this provision to batches of lakes certified under the
proposed new procedure by replacing the term ``certificate'' with the
phrase ``certificate or acceptance of a notice claiming
certification''. Proposed Sec. 80.32(a) would also clarify that any
lake prepared with the color additive covered by the fraudulently
obtained certificate or acceptance would lose its certification.
Current Sec. 80.32(b) provides that if, between the time a
representative sample is taken from a batch of color additive and the
time a certificate for the batch is received by the person to whom it
is issued, the color additive becomes changed in composition, the
certificate shall not be effective, and the changed color additive
shall be considered to be from an uncertified batch. Proposed
Sec. 80.32(b) would continue the applicability of this provision to
batches of lakes certified under the proposed new procedure by amending
the description of the sample to include a sample retained by a firm
claiming certification for a batch of lake and by replacing the word
``a certificate'' by ``a certificate or an acceptance of a notice
claiming certification.'' The agency is also proposing to amend
Sec. 80.32(b) to state that if a certificate or acceptance of a notice
claiming certification for a batch of color additive ceases to be
effective, then any batch of lake prepared with such color additive is
also an uncertified batch.
Current Sec. 80.32(c) provides that if, at any time after a
certificate is received by the person to whom it is issued, any color
additive from the batch covered by the certificate becomes changed in
composition, the certificate expires. Proposed Sec. 80.32(c) would
continue the applicability of this provision to batches of lakes
certified under the proposed new procedure by replacing the term ``a
certificate'' with the phrase ``a certificate or an acceptance of a
notice claiming certification.'' The agency is also proposing to amend
the second sentence in Sec. 80.32(c) to indicate clearly that the
expiration of a certificate or an acceptance of a notice claiming
certification of a batch of color additive would cause any lake
prepared with such color additive to be an uncertified batch.
To allow certain specified uses of the color additive, current
Sec. 80.32(c) provides three exceptions to the expiration of the
certificate when a change in composition occurs. A change in
composition does not cause the certificate to expire if the change in
composition resulted solely from use of the color additive: (1) For
coloring a food, drug, or cosmetic; (2) for the purpose of certifying a
batch of a mixture in which the color additive was used as an
ingredient; or (3) for use in preparing a batch of a mixture for which
exemption from certification has been authorized. Proposed
Sec. 80.32(c) would add another exception to provide that a change in
composition would not cause the certification of a color additive to
expire if the change in composition resulted solely from use of the
color additive as a component or ingredient in a batch of lake for
which certification was claimed under Sec. 80.31(b) of this chapter.
This provision would allow the use of certified batches of straight
color to prepare a lake, or the use of a portion of a certified batch
of lake as an ingredient in another certified batch of lake.
As amended, Sec. 80.32(c) would permit any changes in the straight-
color components of a lake that would normally occur during lake
manufacture under conditions consistent with CGMP. For example, if the
straight color was a sodium salt (e.g. D&C Yellow No. 10), and the lake
was prepared with aluminum cation, this provision would allow for the
change in the cation associated with the straight color from sodium to
aluminum. However, this provision could not be used to justify a claim
for certification of a batch of lake containing a straight color that
had degraded during preparation of the lake. Such a batch of lake would
not meet the requirement in part 74 that lakes be free from impurities
other than those named in the specifications, to the extent that such
impurities may be avoided by CGMP. Therefore, the batch would not
comply with the conditions of Sec. 80.31(b) and could not be a
certified batch.
Current Sec. 80.32(d) provides that a certificate expires if the
package in which the color additive was closed for shipment or delivery
is opened. Current Sec. 80.32(d)(1) through (d)(5) specify five
exceptions to the expiration of the certificate. These exceptions allow
a package of certified color additive to be opened and the color
additive used (1) in coloring a food, drug, or cosmetic (subject to
certain restrictions); (2) for the purpose of certifying a batch made
by repacking the color additive; (3) for the purpose of certifying a
batch of a mixture in which the color additive is used as an
ingredient; (4) for the purpose of preparing a batch of a mixture for
which exemption from certification has been authorized; and (5) when
the package is reopened solely for repackaging by the person to whom
the certificate was issued. Proposed Sec. 80.32(d) would continue the
applicability of these provisions to certified batches of lakes or
certified repacks of such batches by replacing the term ``a
certificate'' by the phrase ``a certificate or an acceptance of a
notice claiming certification.''
Current Secs. 80.32(e), (f), and (g) describe additional conditions
under which a certificate ceases to be effective with respect to a
package of color additive and under which the color additive is
therefore considered to be from an uncertified batch. Proposed
Sec. 80.32(e), (f), and (g) would continue the applicability of these
provisions to batches of lakes certified under the proposed new
procedure by replacing the term ``a certificate'' by the phrase ``a
certificate or an acceptance of a notice claiming certification.''
Current Sec. 80.32(h) describes the consequences of revocation or
amendment of the listing or specifications for a color additive.
Section 80.32(h) states that on the date specified in the order
effecting the revocation or amendment, all certificates for existing
batches and portions of batches of the color additive issued under the
revoked or amended regulations cease to be effective, and any such lots
of the color additive are regarded as uncertified after the date
specified unless a new certificate can be and is obtained in conformity
with the new regulation. Proposed Sec. 80.32(h) would continue the
applicability of this provision to batches of lakes certified under the
proposed new procedure by replacing the term ``a certificate'' by the
phrase ``a certificate or an acceptance of a notice claiming
certification.'' Proposed Sec. 80.32(h) would also provide that any
batch of lake prepared from a batch or portion of a batch of color
additive that was certified under the revoked or amended regulations is
also regarded as uncertified unless a new certificate is obtained.
b. Authority to refuse certification. Certification requirements
are enforced through the provisions of Sec. 80.34 Authority to refuse
certification service. This section currently provides four conditions
for refusing certification service to a firm requesting certification.
Paragraph 80.34(a)(1) authorizes the agency to deny certification
service to a firm that has ``obtained or attempted to obtain a
certificate through fraud or misrepresentation of a material fact.''
[[Page 8401]]
The remaining three paragraphs (Sec. 80.34(a)(2), (a)(3), and (a)(4))
authorize the agency to deny certification service to a firm that
violates the recordkeeping requirements of Sec. 80.39 by falsifying the
required records; failing to keep the records or to make them available
to the agency; or by refusing to permit duly authorized FDA employees
full access to inspect the manufacturing facilities, processes and
formulae involved in the manufacture of color additives and of
intermediates from which such color additives are derived. Proposed
Sec. 80.34 would continue the application of these provisions to firms
certifying batches of lakes under the proposed new procedure by
amending Sec. 80.34 to replace the phrase ``a certificate'' with the
phrase ``a certificate or acceptance of a notice claiming
certification.'' Proposed Sec. 80.34(a)(4) would also authorize FDA to
examine processes and formulae for substrata, as substances from which
color additives are derived.
C. Amendments to Other Regulations
1. Listings in Part 74
a. Listings for FD&C Red No. 40 lakes. Except for FD&C Red No. 40,
all the straight colors used in lakes were provisionally listed in
1960. FD&C Red No. 40 was never provisionally listed and, when FD&C Red
No. 40 was listed (permanently) in 1971 (food and drugs: 36 FR 23552,
December 10, 1971) and 1975 (cosmetics: 39 FR 28278, August 6, 1974,
and 39 FR 44198, December 23, 1974), the lakes of FD&C Red No. 40 were
included, for convenience, in Secs. 74.340, 74.1340, and 74.2340. These
permanent listings for FD&C Red No. 40 lakes cross-reference the
specifications and labeling requirements in the provisional listings
for lakes. For consistency, the agency is proposing to move the current
listings of lakes of FD&C Red No. 40 in Secs. 74.340, 74.1340, and
74.2340 to Secs. 74.50, 74.1050, and 74.2050, respectively, to conform
the permanent listing of the lakes of FD&C Red No. 40 to the permanent
listings for other lakes.
b. Reference to lakes in listings for straight colors. The proposed
permanent listings for lakes (Secs. 74.50, 74.1050, and 74.2050) would
specify the straight colors that are permitted as components of a lake.
The agency tentatively concludes that the regulations for the straight
colors should specify that lakes made with the straight color must
conform to the requirements for lakes (Secs. 74.50, 75.1050, or
74.2050, as appropriate). Therefore, the agency is proposing to amend
the listings in part 74, subpart A, for the straight colors used to
prepare lakes for food use to specify that ``lakes made with (name of
straight color) shall conform to the requirements of Sec. 74.50''; to
amend the listings in part 74, subpart B, for the straight colors used
to prepare lakes for drug use to specify that ``lakes made with (name
of straight color) shall conform to the requirements of Sec. 74.1050'';
and to amend the listings in part 74, subpart C, for the straight
colors used to prepare lakes for cosmetic use to specify that ``lakes
made with (name of straight color) shall conform to the requirements of
Sec. 74.2050.''
c. Listings for eye-area use of lakes. In 1994, the agency
permanently listed the aluminum lakes on alumina of the straight colors
FD&C Blue No. 1 and FD&C Red No. 40 (February 16, 1994, 59 FR 7635) and
FD&C Yellow No. 5 (November 29, 1994, 59 FR 60893), for use in drugs
and cosmetics intended for use in the area of the eye. Because
Sec. 81.1 specifically precludes use of provisionally listed lakes in
eye-area products, these lakes were included in the permanent listings
of the straight color. The agency tentatively concludes that it is
appropriate to include the eye-area uses of lakes with the other
permanently listed uses of lakes and is therefore proposing to move
these eye-area uses from the permanent listings for the straight colors
to Secs. 74.1050 and 74.2050.
2. Color Additive Labeling
Currently, provisionally listed lakes are subject to the general
labeling requirements for color additives in Sec. 70.25. FDA is
proposing to continue the applicability of these requirements to
permanently listed lakes by including a provision in proposed
Secs. 74.50, 74.1050, and 74.2050 to prescribe that the label of a lake
conform to the requirements of Sec. 70.25.
To reflect the proposed deletion of the provisional listings for
color additives, the agency is also proposing to amend Sec. 70.25(a) by
removing the reference to part 81. As a result of the proposed change
in the definition of ``straight color'' and the proposed new definition
of ``listed color,'' the agency is proposing to maintain the general
labeling requirements for color additives by amending Sec. 70.25(a)(1)
and (a)(3) to replace the term ``straight color'' with the term
``listed color.'' As amended, Sec. 70.25(a)(1) would require the label
of a package of lake to include the name of the lake, as prescribed in
part 74 (Secs. 74.50, 74.1050, or 74.2050).
As a result of the proposed new certification procedure for batches
of lakes, the agency is also proposing to amend Sec. 70.25(a)(3), which
requires that the label of certified colors that are subject to a
tolerance (quantitative limitation on use) bear directions to prevent
products to which the color may be added from exceeding the tolerance.
As amended, Sec. 70.25(a)(3) would provide that, where regulations
impose a tolerance for a general or specific use of a straight color,
the amount of a straight color present in a lake would be included in
the total amount of the straight color.
In addition, the agency is proposing to amend Sec. 70.25(d) Special
labeling for color additives not exempt from certification to establish
separate labeling requirements for color additives subject to the
certification procedures of Sec. 80.31(a) and lakes subject to the
certification procedures of Sec. 80.31(b). Proposed Sec. 70.25(d)(1)
would apply to color additives subject to certification under
Sec. 80.31(a) and would incorporate the provisions of current
Sec. 70.25(d). Proposed Sec. 70.25(d)(2) would prescribe special
labeling requirements for lakes subject to certification procedures
under Sec. 80.31(b). The proposed paragraph would require that the
labeling for such lakes include the total color content of the lake,
the amount of color contributed by each straight-color component of the
lake, and FDA's acceptance number for the notice claiming certification
of the batch. The information on the total color content and content of
each straight color in the lake would enable the user of the lake to
comply with any quantitative limitations on the use of the straight-
color component of a lake. This information would also assist the user
in the formulation of products using the lake. The inclusion of the FDA
acceptance number for the notice claiming certification for the batch
would facilitate agency verification of the records and other
information for the batch.
3. Product Labeling
a. Food ingredient labeling. i. Statutory authority. Currently,
lakes are provisionally listed colors subject to certification.
Therefore, under section 403(i) of the act (21 U.S.C. 343), as amended
by the Nutrition Labeling and Education Act of 1990 (Pub. L. 101-535)
(the NLEA), lakes must be listed as ingredients on the label of food
products that contain them. Before the NLEA was enacted, the act
provided that color additives added to food need not be declared
individually by their common or usual names but could be designated by
the collective term ``colorings.'' In 1990, the NLEA amended section
403(i) of the act to exempt from label
[[Page 8402]]
declaration only colors not required to be certified. To implement
amended section 403(i), the agency revised its labeling regulations in
Sec. 101.22 by adding new paragraph (k), which became effective on May
8, 1993. Under Sec. 101.22(k)(1), the lake of a color additive subject
to certification must be individually identified on the food label.
Because all lakes for food use are made from straight colors subject to
certification and are themselves certified color additives, the
presence of a lake in a food product must always be individually
identified on the label of the product under Sec. 101.22(k)(1). The
agency is now proposing to list lakes permanently as color additives
subject to certification. Therefore, in accordance with section 403(i)
of the act (21 U.S.C. 343(i)), the agency is proposing to retain the
requirement that lakes be declared on the food label under their
individual names rather than as ``colorings.''
Section 721(b)(3) of the act (21 U.S.C. 379e(b)(3)) provides that
regulations for the listing of a color additive ``shall, to the extent
deemed necessary * * * to assure the safety of the use or uses for
which a particular color additive is listed, prescribe the conditions
under which such additive may be safely employed for such use or uses
(including, but not limited to * * * directions or other labeling or
packaging requirements for such additive).'' The straight colors FD&C
Yellow No. 5 and FD&C Yellow No. 6 have been reported to cause
hypersensitivity in some individuals. Declaration of the lakes of FD&C
Yellow No. 5 and FD&C Yellow No. 6 on the label of foods that contain
them will provide the means for consumers who are sensitive to these
color additives to identify the foods that contain them and thereby
avoid suffering a reaction. Therefore, the agency tentatively concludes
that such a label declaration requirement is necessary.
Label declaration of the straight color FD&C Yellow No. 5 is
required under Sec. 74.705 for all foods that contain this color
additive, including butter, cheese, and ice cream (foods exempted under
section 403(k) of the act (21 U.S.C. 343(k)) from the requirement to
declare the presence of certified color additives). In the Federal
Register of July 21, 1995 (60 FR 37611), the agency published a
proposal to require declaration of FD&C Yellow No. 6 on the labels of
butter, cheese, and ice cream (hereinafter referred to as the July 1995
proposal). Declaration of FD&C Yellow No. 6 in other foods is already
required under Sec. 101.22(k)(1). The agency notes that both its
original proposal to require the labeling of FD&C Yellow No. 5 in foods
and ingested drugs (42 FR 6835, February 4, 1977) and the pending
proposal to require the labeling of FD&C Yellow No. 6 in butter,
cheese, and ice cream refer to the need for label declaration of the
presence of the color additive in food for humans--whether added as a
straight color, a mixture, or a lake--to enable persons intolerant to
the color additive to minimize exposure to it. Therefore, the agency
tentatively concludes that the lakes of FD&C Yellow No. 5 and FD&C
Yellow No. 6 should be subject to the same label declaration
requirements for foods as the straight colors. Accordingly, this
proposal modifies the July 1995 proposal to include lakes.
Proposed Sec. 74.50(e)(2) would require that the label of food
products for human use that contain a lake declare the presence of the
lake in accordance with Sec. 101.22(k) of this chapter. Proposed
Sec. 74.50(e)(3) would require that the labels of butter, cheese, and
ice cream that contain a lake of FD&C Yellow No. 5 or FD&C Yellow No. 6
declare such lake in the list of ingredients.
ii. Format. Currently, Sec. 101.22(k)(1) provides for the
declaration of certified color additives, including lakes, in the
ingredient listing on the food label and cites part 74 or 82 as the
source of the name of such color additive. In this rulemaking, the
agency is proposing to list lakes permanently in part 74 and to remove
parts 81 and 82. Therefore, the agency is proposing to remove the
reference to part 82 as a source of the name for a certified color
additive for declaration on the food label.
Section 101.22(k)(1) states that it is not necessary to include the
``FD&C'' prefix or the term ``No.'' in the declaration of a color
additive on the food label, but that the term ``Lake'' must be included
in the declaration of a lake. However, the example given in
Sec. 101.22(k)(1) (``Blue 1 Lake'') to illustrate the declaration of a
lake does not include the identity of the precipitant cation, although
the precipitant cation is part of the listed name of the lake under
current Sec. 82.51. In addition, in this rulemaking, the agency is
proposing in Sec. 74.50 to include the substratum as well as the
precipitant cation in the listed name of a lake.
The agency tentatively concludes that the current abbreviated
nomenclature (e.g., Blue 1 Lake) for food ingredient labeling is still
appropriate and that the inclusion of the identity of the precipitant
cation and substratum in the name of the lake on the food label is
unnecessary and may be confusing to consumers. Inclusion of these
components of lakes as part of the name of the lake in the ingredient
list would greatly lengthen the name of the lake on the food label
without providing any additional information about the color additive,
since the agency is proposing to permit only the aluminum cation and
the substratum alumina in lakes for food use.
As discussed in section IV.A.1.d. of this document, the agency is
also proposing in new Sec. 74.50 to allow the use of more than one
straight color in a lake. Accordingly, the agency is proposing to amend
Sec. 101.22(k)(1) to require that all straight colors used to prepare a
lake be included in the name of the lake. Amended Sec. 101.22(k)(1)
would also specify that it is not necessary to include the name of the
precipitant cation or the substratum in the name of a lake when listing
it as an ingredient in a food product. Thus, a lake would be identified
on a food label by a name consisting of the names of the straight
colors (in descending order of predominance) present in the lake
(without the ``FD&C'' designation or the term ``No.'') followed by the
word ``Lake.'' For example, a lake that contains 10 percent FD&C Yellow
No. 5, 5 percent FD&C Blue No. 1, the aluminum cation, and alumina
substratum would be declared on the food label as ``Yellow 5 and Blue 1
Lake.''
b. Cosmetic ingredient labeling. Currently, Sec. 701.3 requires
that the label of each package of a cosmetic bear a declaration of the
name of each ingredient in descending order of predominance. Section
701.3(c) also designates, in order of priority, the sources from which
the names of cosmetic ingredients are to be derived for the purpose of
declaration of ingredients. Under Sec. 701.3(c)(1), if FDA has
established a name for the ingredient in Sec. 701.30, that name is
used. However, Sec. 701.3(c)(1) does not cite the color additive
regulations as the preferred source for names of color additives. The
agency is proposing to correct this oversight by amending Sec. 701.3(c)
to include the color additive listings in parts 73 and 74 as the
preferred source of names for the declaration of ingredients on the
cosmetic label.
Currently, under Sec. 701.3(c)(2) (21 CFR 701.3(c)(2)), a lake is
declared on the cosmetic label by the name under which it is listed in
the CTFA Cosmetic Ingredient Dictionary, 2d ed. (1977). This name is
the same as the listed name of the color additive, which, under
Secs. 82.51, 82.1051, and 82.2051, is formed from the name of the
straight color, the name of the precipitant
[[Page 8403]]
cation, and the word ``lake.'' As discussed in previous sections of
this document, the agency is proposing in Sec. 74.2050(c) to change the
listed name of a lake to include the name of the substrata used in the
lake, and is also proposing to allow the use of more than one straight
color to make a lake. The agency recognizes that these proposed changes
would result in a long listed name for a lake. As with food labels, the
agency is concerned that the additional information that such a name on
a cosmetic label would provide to consumers would be overshadowed by
consumer confusion about the identity and composition of the color
additive.
Unlike lakes added to food (which, under the proposed regulation,
would be permitted to contain only one cation precipitant (aluminum)
and one substratum (alumina)), however, lakes added to cosmetics would
continue to contain a range of possible cation precipitants and
substrata. The straight color and the substrata are the principal
components of the lake by weight, making up over 95 percent of the
total weight of the lake. Currently, the name of a lake provides only
the identity of the straight color and the precipitant. The complete
name of a lake would provide additional information to consumers about
the substrata present in lakes. On the other hand, the space available
for ingredient declaration on a cosmetic label is limited, and under
the proposed new nomenclature that would be required by Sec. 74.2050,
the name of a lake would occupy a significantly greater amount of space
than currently. Furthermore, the amount of space on the label that
would be allocated to declaring the presence of a lake would give undue
prominence to the lake as an ingredient and overshadow the other
ingredients of the cosmetic product, although lakes are not necessarily
more important to the consumer.
Therefore, the agency tentatively concludes that the abbreviated
nomenclature permitted for declaring lakes as ingredients on the food
label under Sec. 101.22(k) should be permitted for cosmetic labels as
well. The agency believes that the abbreviated name would provide
consumers with more understandable information about the identity of
the color additive because it would clearly identify the ingredient as
a color additive and highlight the color component of the lake, which
is its primary characterizing feature from the consumer's point of
view. The agency tentatively finds that adopting uniform nomenclature
for color additives, including lakes, on food and cosmetic ingredient
labels would assist consumers in identifying these ingredients as color
additives. Therefore, the agency tentatively concludes that the
extension of abbreviated nomenclature for ingredient labeling of lakes
to cosmetics as well as foods will provide maximum benefit to
consumers.
For consistency, the agency also tentatively concludes that this
abbreviated nomenclature for cosmetic ingredient labeling should apply
to all certified color additives, not just to lakes. Currently,
straight colors are declared on the cosmetic label by the listed name
of the straight color (e.g., FD&C Blue No. 2). However, as discussed
above, under Sec. 101.22(k) the agency permits the use of abbreviated
names for identifying straight colors in the ingredient statement on
the food label. The agency tentatively concludes that the abbreviated
name now being used on the food label (the listed name without the
prefix ``FD&C'' or ``D&C,'' and without the term ``No.'') would meet
the purpose of ingredient declaration on the cosmetic label to prevent
consumer deception and to facilitate value comparisons (38 FR 28912,
October 17, 1973).
However, for cosmetics, the prefix ``Ext.'' would still be required
as part of the abbreviated name to uniquely identify different color
additives. For example, D&C Yellow No. 7 (21 CFR 74.1707 and 74.2707)
and Ext. D&C Yellow No. 7 (21 CFR 74.1707a and 74.2707a) are different
chemical compounds, although they are both listed as color additives
for use in externally applied drug and cosmetic products. Under the
proposed abbreviated nomenclature, Ext. D&C Yellow No. 7 would be
declared as Ext. Yellow 7, whereas D&C Yellow No. 7 would be declared
as Yellow 7.
Adopting this abbreviated nomenclature for ingredient declaration
of certified colors on cosmetic labels would eliminate the current
inconsistency between the nomenclature used to identify certified
colors on food labels and the nomenclature used on cosmetic labels, as
well as any resulting consumer confusion. Therefore, the agency is
further proposing to adopt as an option, for the purpose of declaring
certified colors as ingredients on the labels of cosmetics, the same
abbreviated nomenclature currently permitted under Sec. 101.22(k) for
declaring certified colors on the food label, except that the ``Ext.''
prefix must be included where applicable. For example, the color
additive D&C Red No. 28 could be declared on the cosmetic label as
``Red 28,'' and a lake containing 10 percent FD&C Yellow No. 5, 5
percent D&C Red No. 28, the precipitant cations aluminum and calcium,
and 50 percent barium sulfate and 35 percent rosin, could be declared
on the cosmetic label as ``Yellow 5 and Red 28 Lake.'' The requirement
that the prefix ``Ext.'' be included on cosmetic labels would not
create an inconsistency with the nomenclature for food labels because,
by definition, ``Ext.'' color additives are for external use and cannot
be used in foods.
To accomplish the changes discussed above, the agency is proposing
to amend Sec. 701.3(c) by establishing new paragraphs (c)(1)(i) and
(c)(1)(ii). Proposed paragraph (c)(1)(ii) would incorporate the
existing citation to Sec. 701.30 as a source of names. Proposed
paragraph Sec. 701.30(c)(1)(i) would identify the color additive
regulations in parts 73 and 74 as the preferred source of names for
color additives. This proposed paragraph would further state that for
color additives listed in part 74 it is not necessary to include the
prefix ``FD&C'' or ``D&C'' or the term ``No.'' in the ingredient
declaration, but that the prefix ``Ext.'' shall be included in the
declaration. For lakes, it would also not be necessary to include the
identity of precipitant cations or substrata, but the term ``Lake''
would have to be included in the name.
c. Labeling of drug products. Under Secs. 201.20 (a) and (b) (21
CFR 201.20 (a) and (b)) and Sec. 74.1705(c), certain over-the-counter
and prescription drug products intended for human use must declare the
presence of FD&C Yellow No. 5 as a color additive. The regulations
specify that the labeling for these drug products shall bear a
statement such as ``Contains FD&C Yellow No. 5 (tartrazine) as a color
additive'' or ``Contains color additives including FD&C Yellow No. 5
(tartrazine),'' and prescribe a more detailed warning that must be
included in the ``Precautions'' section of the labeling.
Under the July 1995 proposal, the labels of certain over-the-
counter and prescription drug products would be required to declare the
presence of FD&C Yellow No. 6 as a color additive. The agency had
previously published a final rule adopting the same requirement for
such drug products (51 FR 41765, November 19, 1986), but subsequently,
in compliance with a stipulation for the dismissal of a lawsuit
challenging the 1986 final rule, the agency published a notice in the
Federal Register of December 6, 1988 (53 FR 49138), announcing that the
requirement would not be enforced pending a reproposal of the action.
[[Page 8404]]
The provisional listings of the lakes of FD&C Yellow No. 5
(Sec. 82.705) and FD&C Yellow No. 6 (Sec. 82.706) do not contain any
reference to the declaration of these lakes in drug products. However,
FDA's proposal to require the labeling of FD&C Yellow No. 5 in foods
and ingested drugs (42 FR 6835, February 4, 1977) explicitly states
that ``a label declaration of the presence of FD&C Yellow No. 5 in food
for humans, whether added as the straight color, a mixture, or a lake,
would enable persons intolerant to FD&C Yellow No. 5 to minimize
exposure to the color.'' The July 1995 proposal contains almost
identical language in the foods section of the proposal (60 FR 37611 at
37613 to 37614). Although these proposals were silent as to whether the
labeling requirement would encompass all forms (straight color,
mixture, or lake) of the color additive when added to drugs, the safety
issue necessitating such labeling in drugs is the same as for foods.
Therefore, the agency tentatively concludes that the presence of FD&C
Yellow No. 5 should be declared as prescribed by Sec. 74.1705 (c)(2)
and (c)(3) and by Sec. 201.20 (a) and (b) when a lake of FD&C Yellow
No. 5 is used in these products, and that the presence of FD&C Yellow
No. 6 should be declared as prescribed by proposed Secs. 74.1706(c)(2)
and 201.20(c) when a lake of FD&C Yellow No. 6 is used. Accordingly,
this proposal modifies the July 1995 proposal to include lakes of FD&C
Yellow No. 5 and FD&C Yellow No. 6. The agency notes that the
declaration of FD&C Yellow No. 5 and FD&C Yellow No. 6 in these drug
products is intended as a warning statement about the presence of these
color additives, not as an ingredient declaration.
To minimize confusion, the agency is proposing that the declaration
for the presence of a lake of FD&C Yellow No. 5 in drug products should
be the same as that required for the straight color in Secs. 74.1705(c)
and 201.20. Therefore, the agency is proposing to require in
Sec. 74.1050(e)(2) that drugs that contain a lake of FD&C Yellow No. 5
be labeled in accordance with Sec. 74.1705 (c)(2) and (c)(3).
Similarly, the agency is proposing to require in Sec. 74.1050(e)(3)
that drugs that contain a lake of FD&C Yellow No. 6 be labeled in
accordance with proposed Sec. 74.1706(c)(2). The agency is also
proposing to amend Sec. 201.20 to state that a drug product that
contains a lake of FD&C Yellow No. 5 or a lake of FD&C Yellow No. 6 is
subject to the same labeling requirements as a drug product that
contains the straight color. Finally, the agency is proposing to amend
Sec. 74.1705 (c)(2) and (c)(3) to clarify that drugs made with a lake
of FD&C Yellow No. 5 are subject to the same label declaration
requirements as drugs made with the straight color, and to modify
proposed Sec. 74.1706(c)(2) to clarify that drugs made with a lake of
FD&C Yellow No. 6 are subject to the same label declaration
requirements as drugs made with the straight color.
Under the current regulations, certain drug products that are also
cosmetics, such as antibacterial mouthwashes and fluoride toothpastes,
need not comply with the label declaration requirements for FD&C Yellow
No. 5 in Secs. 74.1705(c) and 201.20, provided that they comply with
the ingredient labeling provisions for cosmetics in Sec. 701.3. The
pending July 1995 proposal for declaration of FD&C Yellow No. 6 in
ingested drugs contains the same proviso. The agency is proposing to
allow the labeling of such drug/cosmetic products that contain lakes of
FD&C Yellow No. 5 or FD&C Yellow No. 6 to use the abbreviated
nomenclature for ingredient declaration of lakes in proposed
Sec. 701.3(c)(1), which is discussed in section VI.C.3.b. of this
document.
4. Other Amendments
As a result of the proposed change in the definition of ``straight
color'' and the proposed new definition of ``listed color,'' the agency
is also proposing to amend Secs. 70.20, 73.1, and 73.1001 to replace
the term ``straight color'' with the term ``listed color.''
As a result of the deletion of the provisional listings (parts 81
and 82), the agency is also proposing to amend Sec. 178.3297(d) by
removing the references to parts 81 and 82.
VII. Summary of Information Requested
To protect the confidentiality of the requested identity and
process information, interested parties may submit such information, as
well as reference samples of rosin products, directly to the Office of
Cosmetics and Colors (address above).
A. In Situ Manufacturing Processes
As discussed in section V.A.2. of this document, the agency is
aware that some substrata, including aluminum benzoate, alumina, barium
sulfate (blanc fixe), and gloss white, may be currently prepared in
situ during the manufacture of lakes. The agency is proposing
conditions for the in situ preparation of alumina and aluminum benzoate
as substrata and is requesting, as comments on this proposal,
information on appropriate methods of preparation and ingredient
specifications for barium sulfate produced in situ. If such comments
are received, the agency will consider modifying the proposal to permit
the in situ preparation of barium sulfate as a substratum.
B. Identity and Specifications for Rosin
As discussed in section V.A.2.k. of this document, the agency is
requesting, as comments on this proposal, information (e.g., a
manufacturer's product specification sheet or analytical data sheet)
about identity and specifications for any type of rosin that does not
meet the identity and specifications proposed in this document, but
that is currently used as the substratum ``rosin'' under Secs. 82.1051
or 82.2051. The agency is also requesting a 5-pound reference sample of
each type of rosin identified in a comment. Comments should identify
the specific type(s) of rosins used by the lake manufacturer and
describe any treatment of the rosin prior to incorporation in a lake.
Furthermore, the agency requests data concerning the dermal safety of
any rosin intended for use as a diluent in color additives for
externally applied drug use.
If the agency receives satisfactory information for additional
types of rosin, the agency will expand the definition of rosin in its
final action on this rulemaking to provide for the use of the
additional products as substrata in lakes for drug or cosmetic use. In
addition, to alleviate the concerns raised by literature reports of
allergic reactions and dermal irritation caused by some forms of free
rosin, the agency is requesting information on the safety of rosin as a
diluent in color additive mixtures used in externally applied drugs. If
the requested data are received and they demonstrate that rosin used as
a diluent in externally applied drugs is safe, the agency will consider
listing rosin for such use in the final rule.
C. Anions in Precipitants
As discussed above, the agency is proposing to allow only the
anions chloride (Cl-1) and sulfate (SO4-2) for use as
components of precipitants. However, because the provisional listing
regulations did not specify the anions that could be used in lakes, the
agency is requesting comments on the use of other anions in the
preparation of lakes for food, drug, or cosmetic use. This information
should include data to document the current use of such anions in
preparing lakes and to demonstrate their safety for such use. If the
agency receives information to confirm the current safe use of anions
other than chloride and sulfate in lakes, the agency will consider
listing these anions in the final rule.
[[Page 8405]]
VIII. Effective Date
Section 701(e) of the act (21 U.S.C. 371(e)) allows 30 days for the
filing of objections to a final rule listing a color additive and
states that such a final rule may not become effective until the period
for filing objections is over. Thus, the earliest possible effective
date for a final rule listing a color additive is 31 days after
publication. FDA typically sets a longer effective date for changes in
labeling requirements.
In accordance with section 701(e) of the act, the agency is
proposing that the final rule resulting from this proposal become
effective 31 days following its publication, except for the proposed
provisions of Secs. 201.20, 74.1050(e), 74.1705(c), and 74.1706(c)(2)
concerning declaration of lakes of FD&C Yellow No. 5 and FD&C Yellow
No. 6 on the labels of certain drug products, and the proposed
provisions of Secs. 74.50(e)(3) and 74.706(d)(2) concerning declaration
of lakes of FD&C Yellow No. 6 on the labels of butter, cheese, and ice
cream. FDA is proposing that these provisions, which are part of the
rulemaking initiated by the July 1995 proposal (as modified by this
proposal), become effective when the final rule resulting from that
proposal takes effect.
Although this proposal contains changes in the ingredient labeling
provisions applicable to cosmetics, the proposed abbreviated
nomenclature for declaration of lakes as ingredients in these products
is optional, and manufacturers may continue to use the old labeling
nomenclature if they wish. Therefore, FDA tentatively concludes that
the amendments to the labeling regulations for lakes in cosmetics do
not necessitate a delay in the effective date of the final rule.
IX. Inspection of Documents
The documents that FDA considered and relied upon in developing
this proposal are available for inspection at the Center for Food
Safety and Applied Nutrition by appointment with the information
contact person (address above). As provided in Sec. 71.15 (21 CFR
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.
X. Environmental Impact
The agency has determined under 21 CFR 25.24(b)(3) that this action
is of a type that does not individually or cumulatively have a
significant effect on the human environment. Therefore, neither an
environmental assessment nor an environmental impact statement is
required.
XI. Paperwork Reduction Act
This proposed rule contains collections of information that are
subject to review by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act of 1995 (Pub. L. 104-13). Therefore, in
accordance with 44 U.S.C. 3506(c)(2)(B) and 5 CFR part 1320, FDA is
providing below the title, description, and respondent descriptions for
the collections of information contained in this proposal along with an
estimate of the resulting annual collection of information burden.
Included in the estimate is the time needed to review instructions, to
gather the required information, and to disclose the information.
FDA invites comments on the following:
(1) Whether the proposed collection of information is necessary for
the proper performance of the functions of the agency, including
whether the information will have practical utility;
(2) The accuracy of the agency's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used;
(3) Ways to enhance the quality, utility, and clarity of the
information to be collected; and
(4) Ways to minimize the burden of the collection of information on
those who are to respond, including through the use of automated
collection techniques, where appropriate, or other forms of information
technology.
Title: Certification and Labeling Requirements for Color Additive
Lakes.
Description: Section 721(c) of the act requires the certification
of color additives where a certification requirement is necessary in
the interest of the public health. Currently, lakes are subject to
certification under Secs. 80.21 and 80.31 and recordkeeping as required
in Sec. 80.39. The proposed rule would establish a new simplified
procedure for certification of batches of lakes. Under Sec. 80.33 of
the proposed rule, the manufacturer or repacker of a lake would submit
a notice claiming certification, in lieu of a request for
certification. The notice would contain information about the
ingredients and chemical composition of the batch. The manufacturer or
repacker would be required to keep records, including a sample taken
from the batch, to document the information in the notice. After
certification, the manufacturer or repacker would be required to keep
records of the disposition of the batch. The proposal would also
require that these records be made available to FDA upon request.
Because most of the records that would be required by the proposed rule
are already kept in the usual course of business, the agency believes
that the proposed provisions will add only a minor additional record
retention burden for firms subject to the proposed provisions.
Section 721(b)(3) of the act provides that a color additive
regulation shall prescribe the conditions under which the additive may
be safely employed for use in foods, drugs, or cosmetics, including any
labeling or packaging requirements necessary to ensure the safety of
the additive. The presence of FD&C Yellow No. 5 or FD&C Yellow No. 6 in
food has been reported to cause allergic-type reactions. To ensure that
consumers who are sensitive to these color additives will be able to
identify and avoid them, the agency is proposing to require in
Sec. 74.50(e)(3) that lakes of FD&C Yellow No. 5 and FD&C Yellow No. 6
that are used as ingredients in butter, cheese, and ice cream be
declared on the labels of these foods. (Declaration of these lakes in
all foods is already required both by statute and regulation.) However,
because the agency is unaware of any current use of lakes of FD&C
Yellow No. 5 or FD&C Yellow No. 6 in butter, cheese, or ice cream, the
agency tentatively concludes that no burden would result from this
proposed change.
Proposed Sec. 701.3(c)(1)(i) changes the reference for the names
under which color additives, including lakes, are declared on the
cosmetic label, and provides for the optional use of abbreviated
nomenclature for the declaration of color additives as ingredients on
the cosmetic label. Proposed Sec. 701.3(c)(1)(i) would also allow
continued use of the current nomenclature, however. The agency does not
anticipate that cosmetic manufacturers will change their labels
immediately to take advantage of the abbreviated nomenclature; rather,
the agency expects that manufacturers will start using the abbreviated
nomenclature when they institute a label change for some other reason.
Therefore, the agency tentatively concludes that proposed
Sec. 701.3(c)(1)(i) would introduce no startup costs or other burden.
To avoid double-counting, certain labeling provisions in this
proposal have not been included in the burden estimate because they
merely cross-reference labeling requirements contained in other
regulations. Accordingly, proposed Secs. 74.50(e)(1) and (e)(2),
74.1050(e), and 74.2050(d) do
[[Page 8406]]
not appear in the burden estimate table. Provisions that merely
continue existing labeling requirements, such as proposed
Sec. 101.22(k)(1), also have not been included in the burden estimate
for this proposal.
Other proposed labeling changes do not constitute collections of
information because they provide for disclosure of information supplied
by FDA. Proposed Secs. 201.20, 74.1705(c)(2) and (c)(3), and
74.1706(c)(2) would require disclosure of the presence of FD&C Yellow
No. 5 and FD&C Yellow No. 6 on the labels and in the labeling of
certain drug products. The proposed regulations specify the wording of
the required disclosures. Also, proposed Sec. 70.25(d)(2) would require
disclosure, on the package label of the lake, of the number assigned by
FDA to its acceptance of the notice claiming certification for the
batch of lake. These labeling requirements provide for ``public
disclosure of information originally supplied by the Federal government
to the recipient for the purpose of disclosure to the public'' and are,
therefore, exempt from OMB review under 5 CFR 1320.3(c)(2). Finally,
some proposed requirements have been excluded from the burden estimate
because the agency tentatively concludes that the resources necessary
to comply with these requirements would be expended by businesses in
the normal course of their activities and that the reporting,
recordkeeping, or disclosure activities required by the proposed
regulation are, thus, usual and customary (5 CFR 1320.3(b)(2)). For
example, the information on percent total color and percent color from
each straight color used in a batch of lake that must appear on the
package label of the lake under proposed Sec. 70.25(d)(2)(i) and (ii)
is needed by the purchaser of the lake to properly formulate the
purchaser's food, drug, or cosmetic product. Therefore, as a matter of
business necessity, a manufacturer or repacker would obtain and
disclose this information to clients, regardless of FDA requirements.
Description of Respondents: Businesses, including small businesses.
Estimated Annual Reporting Burden
----------------------------------------------------------------------------------------------------------------
Total
Annual Total Operating
CFR Section Number of Frequency Annual Hours per Total and
Respondents per Responses Response Hours Maintenance
Response Costs
----------------------------------------------------------------------------------------------------------------
21 CFR 74.50(e)(3)........................ 0 0 0 0 0 0
21 CFR 80.33.............................. 20 80 1,600 0.25 400 $48,000
21 CFR 701.3(c)(1)(i)..................... 0 0 0 0 0 0
-----------------------
Totals................................ ........... ......... ......... ......... 400 48,000
----------------------------------------------------------------------------------------------------------------
Estimated Annual Recordkeeping Burden
----------------------------------------------------------------------------------------------------------------
Annual Total
CFR Section Number of Frequency of Annual Hours per Total
Recordkeepers Recordkeeping Records Recordkeeper Hours
----------------------------------------------------------------------------------------------------------------
21 CFR 80.22.................................. 20 1 20 2.65 53
21 CFR 80.39.................................. 20 1 20 37.35 747
Totals.................................... ............. ............. ......... 40 800
----------------------------------------------------------------------------------------------------------------
The agency expects that the number of respondents and the annual
burden hours will not change significantly over succeeding years
because it believes that the use of lakes in foods, drugs, and
cosmetics will remain constant. There are no anticipated capital or
startup costs associated with the proposed information collection
requirements.
The agency has submitted copies of the proposed rule to OMB for
review of the portions of the proposal that are within the ambit of the
Paperwork Reduction Act of 1995. Interested persons are requested to
send comments regarding information collection by April 3, 1996, but
not later than May 3, 1996, to the Office of Information and Regulatory
Affairs, OMB, New Executive Office Building, rm. 10235, Washington, DC
20503, ATTN: Desk Officer for FDA.
XII. Comments
As noted in section XI. of this document, interested parties may,
on or before May 3, 1996, submit to the Office of Information and
Regulatory Affairs, OMB (address above) written comments regarding the
collections of information contained in this proposal. For other issues
in the proposed rule, interested persons may, on or before June 3,
1996, submit to the Dockets Management Branch (address above) written
comments regarding this proposal. Four copies of any comments are to be
submitted, except that individuals may submit one copy. Comments are to
be identified with the docket number of the rulemaking or rulemakings
to which the comment is relevant. Comments on modifications to the July
1995 proposal regarding label declaration of FD&C Yellow No. 6 should
be identified with both docket numbers found in brackets in the heading
of this document; comments on other aspects of this proposal should be
identified with docket number 79N-0043 only. Received comments may be
seen in the office above between 9 a.m. and 4 p.m., Monday through
Friday.
In addition, interested persons may, on or before June 3, 1996,
submit to the Office of Cosmetics and Colors (address above) written
comments containing process information relating to the identity and
current use of substrata (including rosin) in lakes, and samples of
such substrata. Written comments regarding the use of anions other than
chloride and sulfate in precipitants may also be submitted to this
address. Two copies of each comment and one 5-pound sample are to be
submitted, and each submission is to be identified with the docket
number (79N-0043) found in
[[Page 8407]]
brackets in the heading of this document.
XIII. 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. Kubo, Y., T. Iijima, ``Dye Elution from Aluminum Lake
Synthetic Food Colors (VI) Brilliant Blue FCF Lakes,'' Shikisai,
60(1): 2-13, 1987.
2. Kubo, Y., M. Shirai, T. Iijima, ``Dye Elution from Aluminum
Lake Synthetic Food Colors (VII) Lakes Produced by One-Step
Method,'' Shikisai, 60(2):83-93, 1987.
3. Kubo, Y., H. Kawaguchi, ``Dye Elution from Aluminum Lake
Synthetic Food Colors (V) Indigo Carmine Lakes,'' Shikisai,
59(11):663-669, 1986.
4. U.S. Patent 2,418,416 to Locke, R. C., Salem, NJ assignor to
E.I. du Pont de Nemours and Co., Wilmington, DE, ``Manufacture of
Azo Lakes,'' April 1, 1947.
5. U.S. Patent 2,478,768 to Locke, R. C., Salem, NJ assignor to
E.I. du Pont de Nemours and Co., Wilmington, DE, ``Manufacture of
Azo Lakes,'' August 9, 1949.
6. Clark, G. R., ``Report on Pure Dye, Impurities, and Substrata
in Pigments,'' Journal of the Association of Official Agricultural
Chemists, 28(4):938-941, 1942.
7. Clark, G. R., ``Report on Lakes and Pigments,'' Journal of
the Association of Official Agricultural Chemists, 24(4):904-906,
1941.
8. Holtzman, H., ``The Hydrous Oxides of Aluminum and Color Lake
Formation,'' agency internal progress report, 1942.
9. Zuckerman, S., ``Color in Cosmetics: Cosmetics, Science and
Technology,'' edited by E. Sagarin, Interscience Publishers, New
York, NY, pp. 539-572, 1974.
10. United States Department of Agriculture, Food Inspection
Decision 76, July 13, 1907.
11. United States Department of Agriculture, ``Certification of
Coal-Tar Colors Begun by Food and Drug Administration,'' information
for the press, May 11, 1939.
12. Faulkner, E. B., ``Coping with International Color
Regulations,'' Cosmetics & Toiletries, 107:45-49, 1992.
13. Memorandum dated June 27, 1988, from the Additives
Evaluation Branch, FDA, to the Division of Food and Color Additives,
FDA.
14. Memoranda dated July 13, 1994, and August 22, 1994, from
Research Chemist, Office of Cosmetics and Colors, FDA (HFS- 128), to
Aydin Orstan, FDA (HFS-217).
15. Memorandum dated December 3, 1986, from the Division of Food
and Color Additives, FDA, to the Division of Colors and Cosmetics,
FDA.
16. Color Index, 3d ed., vol. 4, Society of Dyers and
Colourists, Bradford, Yorkshire, England, pp. 4003, 4009-4011, 4013,
4379, 4417, 4435, 4593-4594, 1971.
17. Marmion, D. M., Handbook of U.S. Colorants for Foods, Drugs,
and Cosmetics, 2d ed., John Wiley and Sons, New York, NY, pp. 48,
64-89, 1984.
18. Food and Drug Administration, ``Report on the Certification
of Color Additives, Foreign and Domestic Manufacturers, fiscal year
1995.''
19. Color Additive Master File No. 9, entry nos. 550, 550A, and
550-addendum 1, dated September 3, 1986, October 8, 1986, and June
3, 1987.
20. Memoranda from the Division of Colors and Cosmetics, FDA, to
the Division of Food and Color Additives, FDA, dated October 2,
1986, November 21, 1986, and October 7, 1987.
21. Food and Drug Administration, Office of Cosmetics and
Colors, ``Intermediates and Subsidiary Colors in FD&C Blue No. 2
Straight Color and Lake,'' September 14, 1995.
22. Lykens, D. N., ``Thermal Stability of FD&C Lake Pigments,''
Plastics Compounding, pp. 35 to 40, November/December, 1986.
23. Memorandum from the Food and Color Additives Review Section,
FDA, to the Direct Additives Branch, FDA, dated March 19, 1991.
24. Memorandum from the Additives Evaluation Branch, FDA, to the
Direct Additives Branch, FDA, dated April 17, 1991.
25. Committee on GRAS List Survey-- Phase III, ``The 1977 Survey
of Industry on the Use of Food Additives,'' vol. 1, National Academy
of Sciences, Washington, DC, pp. 1175 to 1192, 1979.
26. King, J., ``Method for Determination of Color Stability in
Laking; The Results of Experiments with the Method of Establishing
the Stability of Color in Laking for FD&C Red No. 4 and D&C Orange
No. 4,'' January 28, 1980.
27. Food and Drug Administration, ``Report of FY-95
Certification Results for Batches of D&C Lakes of D&C Orange No. 5,
D&C Red Nos. 21, 22, 27 and 28,'' December 1, 1995.
28. Food and Drug Administration, ``Report of FY-95
Certification Results for Batches of D&C Yellow No. 10 Lakes
Prepared from Certified Batches of Straight Color,'' December 1,
1995.
29. The Cosmetic, Toiletry, and Fragrance Association, edited by
Wenninger, J. A., and G. N. McEwen, ``International Cosmetic
Ingredient Dictionary, 5th ed.,'', vol. 1, Washington, DC, p. 640,
1993.
30. Hercules, Product Data Sheet no. 7248, for Dresinate Dry
Powder Soaps.
List of Subjects
21 CFR Part 70
Color additives, Cosmetics, Drugs, Labeling, Packaging and
containers.
21 CFR Part 73
Color additives, Cosmetics, Drugs, Medical devices.
21 CFR Part 74
Color additives, Cosmetics, Drugs, Incorporation by reference.
21 CFR Part 80
Color additives, Cosmetics, Drugs, Reporting and recordkeeping
requirements.
21 CFR Part 81
Color additives, Cosmetics, Drugs.
21 CFR Part 82
Color additives, Cosmetics, Drugs.
21 CFR Part 101
Food Labeling, Nutrition, Reporting and recordkeeping requirements.
21 CFR Part 178
Food additives, Food packaging.
21 CFR Part 201
Drugs, Labeling, Reporting and recordkeeping requirements.
21 CFR Part 701
Cosmetics, Labeling, Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act, the
transitional provisions of the Color Additive Amendments of 1960, and
under authority delegated to the Commissioner of Food and Drugs and
redelegated to the Associate Commissioner for Regulatory Affairs, it is
proposed that 21 CFR parts 70, 73, 74, 80, 81, 82, 101, 178, 201 and
701 be amended as follows:
PART 70--COLOR ADDITIVES
1. The authority citation for 21 CFR part 70 continues to read as
follows:
Authority: Secs. 201, 401, 402, 403, 409, 501, 512, 601, 701,
721 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 341,
342, 343, 348, 351, 360b, 361, 371, 379e).
2. Section 70.3 is amended by revising paragraphs (j), (k), (l),
and (n), and by adding new paragraphs (w) and (x) to read as follows:
Sec. 70.3 Definitions.
* * * * *
(j) The term straight color means a color additive listed in parts
73 or 74 of this chapter, but does not include color additive mixtures
or lakes.
(k) The term mixture means a color additive made by mixing two or
more listed colors, or one or more listed colors and one or more
diluents, without an accompanying chemical reaction.
(l) The term lake means a color additive made by extending one or
more straight colors on one or more substrata by adsorption,
coprecipitation, or chemical combination, but does not include
mixtures.
* * * * *
(n) The term substratum means the substance on which the straight
color in a lake is extended.
* * * * *
[[Page 8408]]
(w) The term listed color means a color additive listed in parts 73
or 74 of this chapter and includes lakes.
(x) The term repack means all or a portion of a batch of certified
color additive that has been sealed in accordance with Sec. 70.20 and
labeled in accordance with Sec. 70.25, but has been reopened solely for
repackaging without further processing, or relabeled for shipment or
delivery, by a person other than the person to whom the certificate or
acceptance of a notice claiming certification was issued.
3. Section 70.20 is amended by revising the section heading and
first sentence to read as follows:
Sec. 70.20 Packaging requirements for listed colors and mixtures
(other than hair dyes).
Listed colors and mixtures shall be packaged in containers which
prevent changes in composition. * * *
* * * * *
4. Section 70.25 is amended in paragraph (a), introductory text, by
removing from the first sentence ``80, and 81'' and adding in its place
``and 80''; in paragraph (a)(1) by removing the words ``straight
color'' and adding in their place the words ``listed color''; in
paragraph (a)(3) by removing the words ``straight color'' and adding in
their place the words ``listed color'' the two times they appear and by
adding a new sentence at the end of the paragraph; and by revising
paragraph (d) to read as follows:
Sec. 70.25 Labeling requirements for color additives (other than hair
dyes).
(a) * * *
(3) * * * The amount of such straight color in a lake shall be
considered part of the total amount of such straight color.
* * * * *
(d) Special labeling for color additives not exempt from
certification. (1) Color additives subject to the certification
procedures of Sec. 80.31(a) of this chapter shall in addition include
in the labeling the lot number assigned by the Color Certification
Branch, Center for Food Safety and Applied Nutrition (CFSAN), Food and
Drug Administration, except that in the case of any mixture for
household use which contains not more than 15 percent of pure color and
which is in packages containing not more than 3 ounces there appears on
the label, a code number which the manufacturer has identified with the
lot number by giving to the Food and Drug Administration written notice
that such code number will be used in lieu of the lot number.
(2) Lakes subject to the certification procedures of Sec. 80.31(b)
of this chapter shall in addition include in the labeling:
(i) The total color content of the lake;
(ii) The amount of color contributed by each straight-color
component of the lake; and
(iii) The FDA acceptance number assigned to the firm's notice
claiming certification for the batch.
PART 73--LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION
5. The authority citation for 21 CFR part 73 continues to read as
follows:
Authority: Secs. 201, 401, 402, 403, 409, 501, 502, 505, 601,
602, 701, 721 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.
321, 341, 342, 343, 348, 351, 352, 355, 361, 362, 371, 379e).
Sec. 73.1 [Amended]
6. Section 73.1 Diluents in color additive mixtures for food use
exempt from certification is amended in the introductory text by
removing the words ``straight color'' and adding in their place the
words ``listed color''.
7. Section 73.1001 is amended in the first sentence of the
introductory text by removing the words ``straight color'' and adding
in their place the words ``listed color'', and in the table in
paragraph (a)(1) by alphabetically adding four new entries to read as
follows:
Sec. 73.1001 Diluents in color additive mixtures for drug use exempt
from certification.
* * * * *
(a) * * *
(1) * * *
----------------------------------------------------------------------------------------------------------------
Substances Definitions and specifications Restrictions
----------------------------------------------------------------------------------------------------------------
* * * * * *
*
Aluminum benzoate.............. As set forth in Sec. 74.1050(a)(3)(ii) of ..................................
this chapter.
Barium sulfate................. As set forth in Sec. 74.1050(a)(3)(iii) of ..................................
this chapter.
* * * * * *
*
Kaolin......................... As set forth in Sec. 74.1050(a)(3)(v) of ..................................
this chapter.
* * * * * *
*
Rosin.......................... As set forth in Sec. 74.1050(a)(3)(vi) of For use only in ingested drugs.
this chapter.
* * * * * *
*
----------------------------------------------------------------------------------------------------------------
* * * * *
PART 74--LISTING OF COLOR ADDITIVES SUBJECT TO CERTIFICATION
8. The authority citation for 21 CFR part 74 continues to read as
follows:
Authority: Secs. 201, 401, 402, 403, 409, 501, 502, 505, 601,
602, 701, 721 of the Federal Food, Drug, and Cosmetic Act.
(21 U.S.C. 321, 341, 342, 343, 348, 351, 352, 355, 361, 362,
371, 379e)
9. Section 74.50 is added to subpart A to read as follows:
Sec. 74.50 Lakes for use in foods.
(a) Identity. (1) Lakes listed in this section are color additives
made by extending one or more certified batches of one or more straight
colors listed in paragraph (a)(2) of this section on a substratum of
alumina that conforms to the requirements of paragraph (a)(3) of this
section using one or more precipitants that form aluminum (Al+3)
cation and chloride (Cl-1) or sulfate (SO4-2) anion.
(2) Lakes listed in this section may contain one or more of the
following straight colors:
(i) FD&C Blue No. 1;
(ii) FD&C Blue No. 2;
(iii) FD&C Green No. 3;
(iv) FD&C Red No. 40;
(v) FD&C Yellow No. 5; and
(vi) FD&C Yellow No. 6.
(3) Lakes listed in this section shall contain the substratum
alumina, which may either conform to the requirements for alumina under
Sec. 73.1010(a)(1) and (b) of this chapter, or may be a suspension in
water of precipitated aluminum hydroxide that is formed from aluminum
sulfate that meets the requirements of the Food Chemicals
[[Page 8409]]
Codex, 2d. ed., 1972, pp. 39-40, which is incorporated by reference in
accordance with 5 U.S.C. 552(a) and 1 CFR part 51, and sodium carbonate
or sodium hydroxide that meets the specifications of the Food Chemicals
Codex, 3d. ed., 1981, p. 280 (sodium carbonate) or p. 287 (sodium
hydroxide), which is incorporated by reference in accordance with 5
U.S.C. 552(a) and 1 CFR part 51. Copies of this publication are
available from the National Academy Press, 2101 Constitution Ave. NW.,
Washington, DC 20418, or may be examined at the Center for Food Safety
and Applied Nutrition's Library, 200 C St. SW., rm. 3321, Washington,
DC, or at the Office of the Federal Register, 800 North Capitol St.
NW., suite 700, Washington, DC.
(4) Color additive mixtures for food use (including dietary
supplements) made with lakes listed in this section may contain only
those diluents that are suitable and that are listed in part 73 of this
chapter as safe for use in color additive mixtures for coloring foods.
Such mixtures shall be used in accordance with paragraph (c) of this
section.
(b) Specifications. Lakes listed in this section shall conform to
the following specifications and shall be free from impurities other
than those named, to the extent that such other impurities may be
avoided by current good manufacturing practice:
(1) Lead (as Pb), not more than 10 parts per million;
(2) Arsenic (as As), not more than 3 parts per million; and
(3) Mercury (as Hg), not more than 1 part per million.
(c) Uses and restrictions. Lakes listed in this section may be
safely used for coloring foods generally (including dietary
supplements) in amounts consistent with current good manufacturing
practice, except that:
(1) They may not be used to color foods for which standards of
identity have been promulgated under section 401 of the act unless
added color is authorized by such standards; and
(2) Any restriction on the use of a straight color shall also apply
to the use of a lake of such straight color. If a lake is prepared
using a single straight color, the lake may be used in the same manner
as permitted for the straight color. If a lake is prepared using more
than one straight color, its use shall be restricted to those uses
common to all of the component straight colors.
(d) Identification. Each lake made as prescribed in paragraph (a)
of this section shall be considered to be a listed color and to be
listed therein under the name that is formed as follows:
(1) The listed names of the straight colors present in the lake (in
descending order of predominance);
(2) The name of the cation precipitant ``Aluminum,'' followed by
the words ``Lake on Alumina.'' (For example, the name of a lake
prepared by the extension of FD&C Yellow No. 5 and FD&C Blue No. 1 on
alumina using aluminum chloride as a precipitant is ``FD&C Yellow No. 5
and FD&C Blue No. 1 Aluminum Lake on Alumina.'')
(e) Labeling. (1) The label of each lake listed in this section and
any mixtures prepared from them that are intended solely or in part for
coloring purposes shall conform to the requirements of Sec. 70.25 of
this chapter.
(2) Foods for human use that contain lakes listed in this section
shall declare the presence of such lakes in accordance with
Sec. 101.22(k)(1) of this chapter.
(3) Butter, cheese, and cream that contain a lake of FD&C Yellow
No. 5 or FD&C Yellow No. 6 shall be labeled in accordance with
Sec. 101.22(k)(1) of this chapter.
(f) Certification. All batches of lakes listed in this section
shall be certified in accordance with regulations in part 80 of this
chapter.
10. Section 74.101 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.101 FD&C Blue No. 1.
(a) * * *
(3) Lakes made with FD&C Blue No. 1 shall conform to the
requirements of Sec. 74.50.
* * * * *
11. Section 74.102 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.102 FD&C Blue No. 2.
(a) * * *
(3) Lakes made with FD&C Blue No. 2 shall conform to the
requirements of Sec. 74.50.
* * * * *
12. Section 74.203 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.203 FD&C Green No. 3.
(a) * * *
(3) Lakes made with FD&C Green No. 3 shall conform to the
requirements of Sec. 74.50.
* * * * *
13. Section 74.340 is amended by revising paragraph (a)(3); in
paragraph (d) by removing the words ``lakes or''; and in paragraph (e)
by removing the words ``and lakes thereof'', to read as follows:
Sec. 74.340 FD&C Red No. 40.
(a) * * *
(3) Lakes made with FD&C Red No. 40 shall conform to the
requirements of Sec. 74.50.
* * * * *
14. Section 74.705 is amended by revising paragraph (a)(3) to read
as follows:
Sec. 74.705 FD&C Yellow No. 5.
(a) * * *
(3) Lakes made with FD&C Yellow No. 5 shall conform to the
requirements of Sec. 74.50.
* * * * *
15. Section 74.706 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.706 FD&C Yellow No. 6.
(a) * * *
(3) Lakes made with FD&C Yellow No. 6 shall conform to the
requirements of Sec. 74.50.
* * * * *
16. Section 74.1050 is added to subpart B to read as follows:
Sec. 74.1050 Lakes for use in drugs.
(a) Identity. (1) Lakes listed in this section are color additives
made by extending one or more certified batches of one or more straight
colors specified in paragraph (a)(2) of this section on one or more
substrata specified in paragraph (a)(3) of this section, using one or
more precipitants that form aluminum (Al+3), barium (Ba+2),
calcium (Ca+2), potassium (K+1), sodium (Na+1),
strontium (Sr+2), or zirconium (Zr+4) cation, and chloride
(Cl-1) or sulfate (SO4-2) anion.
(2) Lakes listed in this section may contain one or more of the
following straight colors:
(i) FD&C Blue No. 1;
(ii) FD&C Blue No. 2;
(iii) FD&C Green No. 3;
(iv) FD&C Yellow No. 5;
(v) FD&C Yellow No. 6;
(vi) FD&C Red No. 4;
(vii) FD&C Red No. 40;
(viii) D&C Blue No. 4;
(ix) D&C Orange No. 4;
(x) D&C Orange No. 5;
(xi) D&C Orange No. 10;
(xii) D&C Red No. 6;
(xiii) D&C Red No. 7;
(xiv) D&C Red No. 21;
(xv) D&C Red No. 22;
(xvi) D&C Red No. 27;
(xvii) D&C Red No. 28;
(xviii) D&C Red No. 31;
(xix) D&C Red No. 33;
(xx) D&C Red No. 34; and
(xxi) D&C Yellow No. 10.
(3) Lakes listed in this section may contain one or more of the
following substrata:
[[Page 8410]]
(i) Alumina that conforms to the requirements of Sec. 74.50(a)(3)
of this chapter; and
(ii) Aluminum benzoate that is prepared from aluminum chloride or
aluminum sulfate that conforms to the requirements of the United States
Pharmacopeia, 23d ed. (1995), p. 64 (aluminum chloride) or p. 68
(aluminum sulfate), which is incorporated by reference in accordance
with 5 U.S.C. 552(a) and 1 CFR part 51, and benzoic acid that conforms
to the requirements of the United States Pharmacopeia, 23d ed. (1995),
pp. 176 and 177, which is incorporated by reference in accordance with
5 U.S.C. 552(a) and 1 CFR part 51. Copies are available from the United
States Pharmacopoeial Convention, Inc., 12601 Twinbrook Pkwy.,
Rockville, MD 20852, or may be examined at the Center for Food Safety
and Applied Nutrition's Library, 200 C St. SW., rm. 3321, Washington,
DC, or at the Office of the Federal Register, 800 North Capitol St.
NW., suite 700, Washington, DC.
(iii) Barium sulfate that conforms to the requirements of the
United States Pharmacopeia, 23d ed. (1995), pp. 165 and 166, which is
incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR
part 51. The availability of this incorporation by reference is given
in paragraph (a)(3)(ii) of this section.
(iv) Calcium carbonate that conforms to the requirements of
Sec. 73.1070(a)(1) and (b) of this chapter.
(v) Kaolin that conforms to the requirements of the United States
Pharmacopeia, 23d ed. (1995), p. 863, which are incorporated by
reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. The
availability of this incorporation by reference is given in paragraph
(a)(3)(ii) of this section.
(vi) Rosin, which is the pale, cream-colored sodium soap of the
residue left after distilling off the volatile oil from the oleoresin
obtained from Pinus palustris and other species of Pinus, and which
conforms to the following specifications:
(A) Solids, not less than 95 percent;
(B) Acid number, not greater than 7.5; and
(C) Free alkali, not greater than 2.5 percent.
(vii) Talc that conforms to the requirements of Sec. 73.1550(a)(1)
and (b) of this chapter.
(viii) Titanium dioxide that conforms to the requirements of
Sec. 73.575 (a)(1) and (b) of this chapter.
(ix) Zinc oxide that conforms to the requirements of
Sec. 73.1991(a)(1) and (b) of this chapter.
(4) Color additive mixtures for drug use made with lakes listed in
this section may contain only those diluents that are suitable and that
are listed in part 73 of this chapter as safe for use in color additive
mixtures for coloring drugs. Such mixtures shall be used in accordance
with paragraph (c) of this section.
(b) Specifications. Lakes listed in this section shall conform to
the following specifications and shall be free from impurities other
than those named, to the extent that such other impurities may be
avoided by current good manufacturing practice:
(1) Lead (as Pb), not more than 20 parts per million;
(2) Arsenic (as As), not more than 3 parts per million;
(3) Mercury (as Hg), not more than 1 part per million; and
(4) For a lake that contains a barium salt, soluble barium (in
dilute HCl) as BaCl2, not more than 0.05 percent.
(c) Uses and restrictions. Lakes listed in this section may be
safely used for coloring drugs generally in amounts consistent with
current good manufacturing practice, except that:
(1) Any restriction on the use of a straight color shall also apply
to the use of a lake of such straight color. If a lake is prepared
using a single straight color, the lake may be used in the same manner
as permitted for the straight color. If a lake is prepared using more
than one straight color, its use shall be restricted to those uses
common to all of the component straight colors. (For example, a lake
produced using two straight colors, one listed for use in coloring
drugs generally and one listed for use in coloring externally applied
drugs only, may be used only for coloring externally applied drugs.)
(2) Where regulations impose quantitative limitations for a general
or specific use of a straight color, the amount of such straight color
in a lake shall be considered part of the total amount of such straight
color in a drug product.
(3) The aluminum lakes on alumina of FD&C Blue No. 1, FD&C Red No.
40, and FD&C Yellow No. 5, prepared in accordance with the requirements
of Sec. 74.50, may be safely used for coloring drugs intended for use
in the area of the eye, in amounts consistent with current good
manufacturing practice. Use of these lakes in the area of the eye is
subject to the limitations in Sec. 70.5 (b) and (c) of this chapter and
does not include use in articles intended for use in injections or as a
surgical suture in the area of the eye.
(d) Identification. Each lake made as prescribed in paragraph (a)
of this section shall be considered to be a listed color and to be
listed therein under the name that is formed as follows:
(1) The listed names of the straight colors present in the lake (in
descending order of predominance);
(2) The names of the cations of the precipitants, followed by the
words ``Lake on ______'';
(3) The names of the substrata (in descending order of
predominance). (For example: The name of a lake prepared by the
extension of FD&C Red No. 40 and D&C Orange No. 5 on alumina and
titanium dioxide using aluminum chloride and calcium chloride as
precipitants is ``FD&C Red No. 40 and D&C Orange No. 5 Aluminum/Calcium
Lake on Alumina and Titanium Dioxide.'')
(e) Labeling. (1) The label of each lake listed in this section and
any mixtures prepared from them that are intended solely or in part for
coloring purposes shall conform to the requirements of Sec. 70.25 of
this chapter.
(2) Drugs that contain a lake of FD&C Yellow No. 5 shall be labeled
in accordance with Sec. 74.1705 (c)(2) and (c)(3).
(3) Drugs that contain a lake of FD&C Yellow No. 6 shall be labeled
in accordance with Sec. 74.1706(c)(2).
(f) Certification. All batches of lakes listed in this section
shall be certified in accordance with regulations in part 80 of this
chapter.
17. Section 74.1101 is amended by adding a new paragraph (a)(4), by
removing paragraphs (b)(2) and (c)(2) and redesignating paragraph
(b)(1) and (c)(1) as paragraphs (b) and (c), respectively, to read as
follows:
Sec. 74.1101 FD&C Blue No. 1.
(a) * * *
(4) Lakes made with FD&C Blue No. 1 shall conform to the
requirements of Sec. 74.1050.
* * * * *
18. Section 74.1102 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1102 FD&C Blue No. 2.
(a) * * *
(3) Lakes made with FD&C Blue No. 2 shall conform to the
requirements of Sec. 74.1050.
* * * * *
19. Section 74.1104 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1104 FD&C Blue No. 4.
(a) * * *
(3) Lakes made with FD&C Blue No. 4 shall conform to the
requirements of Sec. 74.1050.
* * * * *
[[Page 8411]]
20. Section 74.1203 is amended by adding a new paragraph (a)(3) to
read as follows:
Sec. 74.1203 FD&C Green No. 3.
(a) * * *
(3) Lakes made with FD&C Green No. 3 shall conform to the
requirements of Sec. 74.1050.
* * * * *
21. Section 74.1254 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1254 D&C Orange No. 4.
(a) * * *
(3) Lakes made with D&C Orange No. 4 shall conform to the
requirements of Sec. 74.1050.
* * * * *
22. Section 74.1255 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1255 D&C Orange No. 5.
(a) * * *
(3) Lakes made with D&C Orange No. 5 shall conform to the
requirements of Sec. 74.1050.
* * * * *
23. Section 74.1260 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1260 D&C Orange No. 10.
(a) * * *
(3) Lakes made with D&C Orange No. 10 shall conform to the
requirements of Sec. 74.1050.
* * * * *
24. Section 74.1304 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1304 FD&C Red No. 4.
(a) * * *
(3) Lakes made with FD&C Red No. 4 shall conform to the
requirements of Sec. 74.1050.
* * * * *
25. Section 74.1306 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1306 D&C Red No. 6.
(a) * * *
(3) Lakes made with D&C Red No. 6 shall conform to the requirements
of Sec. 74.1050.
* * * * *
26. Section 74.1307 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1307 D&C Red No. 7.
(a) * * *
(3) Lakes made with D&C Red No. 7 shall conform to the requirements
of Sec. 74.1050.
* * * * *
27. Section 74.1321 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1321 D&C Red No. 21.
(a) * * *
(3) Lakes made with D&C Red No. 21 shall conform to the
requirements of Sec. 74.1050.
* * * * *
28. Section 74.1322 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1322 D&C Red No. 22.
(a) * * *
(3) Lakes made with D&C Red No. 22 shall conform to the
requirements of Sec. 74.1050.
* * * * *
29. Section 74.1327 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1327 D&C Red No. 27.
(a) * * *
(3) Lakes made with D&C Red No. 27 shall conform to the
requirements of Sec. 74.1050.
* * * * *
30. Section 74.1328 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1328 D&C Red No. 28.
(a) * * *
(3) Lakes made with D&C Red No. 28 shall conform to the
requirements of Sec. 74.1050.
* * * * *
31. Section 74.1331 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1331 D&C Red No. 31.
(a) * * *
(3) Lakes made with D&C Red No. 31 shall conform to the
requirements of Sec. 74.1050.
* * * * *
32. Section 74.1333 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1333 D&C Red No. 33.
(a) * * *
(3) Lakes made with D&C Red No. 33 shall conform to the
requirements of Sec. 74.1050.
* * * * *
33. Section 74.1334 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1334 D&C Red No. 34.
(a) * * *
(3) Lakes made with D&C Red No. 34 shall conform to the
requirements of Sec. 74.1050.
* * * * *
34. Section 74.1340 is amended by revising paragraph (a)(3); by
removing paragraph (b)(2); by redesignating paragraph (b)(1) as
paragraph (b); by amending newly redesignated paragraph (b) by removing
the phrase ``and FD&C Red No. 40 Aluminum Lake''; by amending paragraph
(c) by removing the phrase ``lakes or''; and by amending paragraph (d)
by removing the phrase ``and lakes thereof'' to read as follows:
Sec. 74.1340 FD&C Red No. 40.
(a) * * *
(3) Lakes made with FD&C Red No. 40 shall conform to the
requirements of Sec. 74.1050.
* * * * *
35. Section 74.1705 is amended by revising paragraph (a)(2); by
removing paragraph (b)(2); by redesignating paragraph (b)(1) as
paragraph (b); and by removing in the first sentence of paragraph
(c)(2) and paragraph (c)(3), the phrase ``containing FD&C Yellow No.
5'' and adding in its place the phrase ``containing FD&C Yellow No. 5
or a lake of FD&C Yellow No. 5''.
Sec. 74.1705 FD&C Yellow No. 5.
(a) * * *
(2) Lakes made with FD&C Yellow No. 5 shall conform to the
requirements of Sec. 74.1050.
* * * * *
36-37. Section 74.1706 is amended by adding new paragraphs (a)(3)
and (c)(2) to read as follows:
Sec. 74.1706 FD&C Yellow No. 6.
(a) * * *
(3) Lakes made with FD&C Yellow No. 6 shall conform to the
requirements of Sec. 74.1050.
* * * * *
(c) * * *
(2) The label of over-the-counter and prescription drug products
intended for human use and administered orally, nasally, rectally, or
vaginally containing FD&C Yellow No. 6, or a lake of FD&C Yellow No. 6,
shall specifically declare the presence of FD&C Yellow No. 6 by listing
the color additive using the name FD&C Yellow No. 6. The labels of
certain drug products subject to this labeling requirement that are
also cosmetics, such as antibacterial mouthwashes and fluoride
toothpastes, need not comply with this requirement provided they comply
with the requirements of Sec. 701.3 of this chapter.
38. Section 74.1710 is amended by adding new paragraph (a)(3) to
read as follows:
Sec. 74.1710 D&C Yellow No. 10.
(a) * * *
[[Page 8412]]
(3) Lakes made with D&C Yellow No. 10 shall conform to the
requirements of Sec. 74.1050.
* * * * *
39. Section 74.2050 is added to subpart C to read as follows:
Sec. 74.2050 Lakes for use in cosmetics.
(a) Identity and specifications. Lakes listed in this section shall
conform in identity and specifications to the requirements of
Sec. 74.1050(a)(1), (a)(2), (a)(3), and (b), except that the straight
color FD&C Blue No. 2 shall not be a component of such lakes.
(b) Uses and restrictions. Lakes listed in this section may be
safely used for coloring cosmetics generally in amounts consistent with
current good manufacturing practice, except that:
(1) Any restriction on the use of a straight color shall also apply
to the use of a lake of such straight color. If a lake is prepared
using a single straight color, the lake may be used in the same manner
as permitted for the straight color. If a lake is prepared using more
than one straight color, its use shall be restricted to those uses
common to all of the component straight colors. (For example, a lake
produced using two straight colors, one listed for use in coloring
cosmetics generally and one listed for use in coloring externally
applied cosmetics only, may be used only for coloring externally
applied cosmetics.)
(2) Where regulations impose quantitative limitations for a general
or specific use of a straight color, the amount of such straight color
in a lake shall be considered a part of the total amount of such
straight color in a cosmetic product.
(3) The aluminum lakes on alumina of FD&C Blue No. 1, FD&C Red No.
40, and FD&C Yellow No. 5, prepared in accordance with the requirements
of Sec. 74.50, may be safely used for coloring cosmetics intended for
use in the area of the eye, in amounts consistent with current good
manufacturing practice. Use of these lakes in the area of the eye is
subject to the limitations in Sec. 70.5(b) and (c) of this chapter, and
does not include use in articles intended for use in injections or as a
surgical suture in the area of the eye.
(c) Identification. Each lake made as prescribed in paragraph (a)
of this section shall be considered to be a listed color and to be
listed therein under the name that is formed as prescribed in
Sec. 74.1050(d).
(d) Labeling. (1) The label of each lake listed in this section and
any mixtures prepared from that are intended solely or in part for
coloring purposes shall conform to the requirements of Sec. 70.25 of
this chapter.
(2) Cosmetics that contain lakes listed in this section shall
declare the presence of such lakes in accordance with
Sec. 701.3(c)(1)(i) of this chapter.
(e) Certification. All batches of lakes listed in this section
shall be certified in accordance with regulations in part 80 of this
chapter.
40. Section 74.2101 is amended by removing paragraphs (b)(2) and
(c)(2); by redesignating paragraphs (a), (b)(1), and (c)(1) as
paragraphs (a)(1), (b), and (c), respectively; and by adding new
paragraph (a)(2) to read as follows:
Sec. 74.2101 FD&C Blue No. 1.
(a) * * *
(2) Lakes made with FD&C Blue No. 1 shall conform to the
requirements of Sec. 74.2050.
* * * * *
41. Section 74.2104 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2) to read as follows:
Sec. 74.2104 D&C Blue No. 4.
(a) * * *
(2) Lakes made with D&C Blue No. 4 shall conform to the
requirements of Sec. 74.2050.
* * * * *
42. Section 74.2203 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2) to read as follows:
Sec. 74.2203 FD&C Green No. 3.
(a) * * *
(2) Lakes made with FD&C Green No. 3 shall conform to the
requirements of Sec. 74.2050.
* * * * *
43. Section 74.2254 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2) to read as follows:
Sec. 74.2254 D&C Orange No. 4.
(a) * * *
(2) Lakes made with D&C Orange No. 4 shall conform to the
requirements of Sec. 74.2050.
* * * * *
44. Section 74.2255 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2) to read as follows:
Sec. 74.2255 D&C Orange No. 5.
(a) * * *
(2) Lakes made with D&C Orange No. 5 shall conform to the
requirements of Sec. 74.2050.
* * * * *
45. Section 74.2260 is amended by redesignating paragraph (a) as
paragraph (a)(1) and adding new paragraph (a)(2) to read as follows:
Sec. 74.2260 D&C Orange No. 10.
(a) * * *
(2) Lakes made with D&C Orange No. 10 shall conform to the
requirements of Sec. 74.2050.
* * * * *
46. Section 74.2304 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2) to read as follows:
Sec. 74.2304 FD&C Red No. 4.
(a) * * *
(2) Lakes made with FD&C Red No. 4 shall conform to the
requirements of Sec. 74.2050.
* * * * *
47. Section 74.2306 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2) to read as follows:
Sec. 74.2306 D&C Red No. 6.
(a) * * *
(2) Lakes made with D&C Red No. 6 shall conform to the requirements
of Sec. 74.2050.
* * * * *
48. Section 74.2307 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2) to read as follows:
Sec. 74.2307 D&C Red No. 7.
(a) * * *
(2) Lakes made with D&C Red No. 7 shall conform to the requirements
of Sec. 74.2050.
* * * * *
49. Section 74.2321 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2) to read as follows:
Sec. 74.2321 D&C Red No. 21.
(a) * * *
(2) Lakes made with D&C Red No. 21 shall conform to the
requirements of Sec. 74.2050.
* * * * *
50. Section 74.2322 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2) to read as follows:
Sec. 74.2322 D&C Red No. 22.
(a) * * *
(2) Lakes made with D&C Red No. 22 shall conform to the
requirements of Sec. 74.2050.
* * * * *
51. Section 74.2327 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2) to read as follows:
[[Page 8413]]
Sec. 74.2327 D&C Red No. 27.
(a) * * *
(2) Lakes made with D&C Red No. 27 shall conform to the
requirements of Sec. 74.2050.
* * * * *
52. Section 74.2328 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2) to read as follows:
Sec. 74.2328 D&C Red No. 28.
(a) * * *
(2) Lakes made with D&C Red No. 28 shall conform to the
requirements of Sec. 74.2050.
* * * * *
53. Section 74.2331 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2) to read as follows:
Sec. 74.2331 D&C Red No. 31.
(a) * * *
(2) Lakes made with D&C Red No. 31 shall conform to the
requirements of Sec. 74.2050.
* * * * *
54. Section 74.2333 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2) to read as follows:
Sec. 74.2333 D&C Red No. 33.
(a) * * *
(2) Lakes made with D&C Red No. 33 shall conform to the
requirements of Sec. 74.2050.
* * * * *
55. Section 74.2334 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2) to read as follows:
Sec. 74.2334 D&C Red No. 34.
(a) * * *
(2) Lakes made with D&C Red No. 34 shall conform to the
requirements of Sec. 74.2050.
* * * * *
56. Section 74.2340 is amended by revising paragraph (a)(2); by
removing in the introductory text of paragraph (b) the phrase ``except
that only FD&C Red No. 40 and FD&C Red No. 40 Aluminum Lake may be
safely used in coloring'' and adding in its place the word
``including'', in paragaph (b)(2) by removing the words ``additives''
and ``their'' and adding in their place the words ``additive'' and
``its'', respectively, to read as follows:
Sec. 74.2340 FD&C Red No. 40.
(a) * * *
(2) Lakes made with FD&C Red No. 40 shall conform to the
requirements of Sec. 74.2050.
* * * * *
57. Section 74.2705 is amended by redesignating paragraph (a) as
paragraph (a)(1) and by adding new paragraph (a)(2), by removing
paragraph (b)(2) and (c)(2) and redesignating paragraphs (b)(1) and
(c)(1) as paragraphs (b) and (c), respectively, to read as follows:
Sec. 74.2705 FD&C Yellow No. 5.
(a) * * *
(2) Lakes made with FD&C Yellow No. 5 shall conform to the
requirements of Sec. 74.2050.
* * * * *
58-59. Section 74.2706 is amended by redesignating paragraph (a) as
paragraph(a)(1) and by adding new paragraph (a)(2) to read as follows:
Sec. 74.2706 FD&C Yellow No. 6.
(a) * * *
(2) Lakes made with FD&C Yellow No. 6 shall conform to the
requirements of Sec. 74.2050.
* * * * *
60. Section 74.2710 is amended by redesignating paragraph (a) as
paragraph(a)(1) and by adding a new paragraph (a)(2) to read as
follows:
Sec. 74.2710 D&C Yellow No. 10.
(a) * * *
(2) Lakes made with D&C Yellow No. 10 shall conform to the
requirements of Sec. 74.2050.
* * * * *
PART 80--COLOR ADDITIVE CERTIFICATION
61. The authority citation for 21 CFR Part 80 continues to read as
follows:
Authority: Secs. 701, 721 of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 371, 379e).
62. Section 80.10 is amended in paragraph (a) by revising the
paragraph heading and by removing the phrase ``and (j)(2)''; in
paragraph (b), introductory text, by revising the paragraph heading and
by removing ``Sec. 80.21(j)(3) and (j)(4)'' and adding in its place
``Sec. 80.21(j)(2) and (j)(3)''; by redesignating paragraphs (c), (d),
(e), and (f) as paragraphs (d), (e), (f), and (g), respectively, by
amending newly redesignated paragraph (d) by removing the phrase ``(a)
and (b)'' and adding in its place the phrase ``(a), (b), and (c)'', and
by adding new paragraph (c) to read as follows:
Sec. 80.10 Fees for certification services.
(a) Fees for straight colors. * * *
* * * * *
(b) Fees for repacks of certified straight colors and color
additive mixtures. * * *
* * * * *
(c) Fees for lakes and repacks of certified lakes. The fee for the
services provided under the regulations in this part in the case of
each notice claiming certification submitted in accordance with
Sec. 80.33 shall be $30.00.
* * * * *
63. Section 80.21 is amended in paragraph (g)(1) by removing the
phrase ``and lakes''; by amending paragraph (g)(2) by adding the words
``of straight colors'' at the end of the sentence; by revising
paragraph (h)(1); by removing paragraph (h)(2) and redesignating
paragraphs (h)(3) and (h)(4) as paragraphs (h)(2) and (h)(3),
respectively; by revising newly redesignated paragraph (h)(3); by
amending paragraph (j), introductory text, by removing the words ``a
lake,'' and by removing the phrase ``previously certified color
additive'' and adding in its place the phrase ``previously certified
straight color''; by removing paragraph (j)(2) and redesignating
paragraphs (j)(3) and (j)(4) as paragraphs (j)(2) and (j)(3),
respectively; and by revising the paragraph heading of newly designated
paragraph (j)(2) to read as follows:
Sec. 80.21 Request for certification.
* * * * *
(h) * * *
(1) The name of a straight color shall be the name of the color
additive as listed in part 74 of this chapter.
* * * * *
(3) The name of a repack shall be the name described in paragraph
(h)(1) or (h)(2) of this section, whichever is applicable.
* * * * *
(j) * * *
(2) Request for certification of a repack of a batch of certified
straight color. * * *
* * * * *
64. Section 80.22 is revised to read as follows:
Sec. 80.22 Samples to accompany requests for certification or to be
held as records.
(a) Straight colors and their mixtures and repacks. A sample of a
batch of color additive which is to accompany a request for
certification shall:
(1) Be taken only after such batch has been so thoroughly mixed as
to be of uniform composition throughout;
(2) Be held under the control of the person requesting
certification until certified; and
(3) Be labeled to show:
(i) The name of the color additive;
(ii) The manufacturer's batch number;
(iii) The quantity of such batch;
[[Page 8414]]
(iv) The name and post office address of the person requesting
certification of such batch; and
(v) Be accompanied by any label or labeling intended to be used.
(b) Lakes and their repacks. A sample of a batch of lake that is to
be held by a firm claiming certification for the batch shall:
(1) Be taken prior to submission of the notice claiming
certification;
(2) Be taken only after such batch has been so thoroughly mixed as
to be of uniform composition throughout;
(3) Be sealed and stored in such a manner as to prevent change in
composition;
(4) Be held by the firm claiming certification for the batch, as
required by Sec. 80.39(b)(3); and
(5) Be labeled to show:
(i) The name of the lake;
(ii) The percent total color for the batch and, if the batch
contains more than one straight color, the percent color in the batch
for each straight color;
(iii) The firm's batch number and the date the sample was taken;
(iv) The quantity of the batch;
(v) The name and place of business of the firm claiming
certification for the batch;
(vi) A copy of any label or labeling intended to be used with the
batch; and
(vii) After receipt of an acceptance of the notice claiming
certification for the batch, FDA's acceptance number.
65. Section 80.31 is amended in paragraph (a) by adding a new
heading; by removing in paragraph (a)(2) in the phrase ``parts 81 and
82'' and adding in its place ``part 74'', by removing in paragraph
(a)(3) the phrase ``81, and 82'', by revising paragraph (b), and by
adding new paragraph (c) to read as follows:
Sec. 80.31 Certification.
(a) Straight colors and their mixtures and repacks. * * *
* * * * *
(b) Lakes and their repacks. If the Commissioner determines, after
such investigations as the Commissioner considers to be necessary,
that:
(1) A notice submitted in accordance with Sec. 80.33 appears to
contain no untrue statement of a material fact;
(2) Such lake conforms to the specifications and any other
conditions set forth therefor in part 74 of this chapter;
(3) The manufacturer of the lake is the firm that was issued the
certificate for each batch of straight color used in the lake;
(4) The manufacturer or repacker of the batch has complied with the
notification requirements in Sec. 80.33 and the recordkeeping
requirements in Sec. 80.39; and
(5) The batch covered by such notice otherwise appears to comply
with the regulations in this chapter, the Commissioner shall issue to
the firm that submitted the notice, an acceptance showing the
acceptance number assigned to such notice. Upon issuance of such an
acceptance, the batch covered by the notice, subject to the terms,
conditions and restrictions prescribed by part 74 of this chapter, is a
certified batch.
(c) If the Commissioner determines, after such investigation as the
Commissioner considers to be necessary, that a request submitted in
accordance with Sec. 80.21, or the batch of color additive covered by
such request, does not comply with the requirements prescribed by
paragraph (a) of this section for the issuance of a certificate, or
that a notice submitted in accordance with Sec. 80.33, or the batch of
lake covered by such notice, does not comply with the requirements
prescribed by paragraph (b) of this section for the issuance of an
acceptance of the notice, the Commissioner shall refuse to certify such
batch and shall give notice thereof to the person who submitted such
request, or such notice, stating the Commissioner's reasons for
refusal. Any person who contests such refusal shall have an opportunity
for a regulatory hearing before the Food and Drug Administration
pursuant to part 16 of this chapter.
66. Section 80.32 is amended by revising the section heading and
paragraphs (a), (b), (c), and the introductory text of paragraph (d);
in paragraphs (e), (f), introductory text, and (g) by adding the words
``or an acceptance of a notice claiming certification'' after the words
``A certificate''; and in paragraph (h) by revising the first sentence
to read as follows:
Sec. 80.32 Limitations of certification.
(a) If a certificate or an acceptance of a notice claiming
certification is obtained through fraud or misrepresentation of a
material fact, such certificate or acceptance shall not be effective,
and a color additive from the batch on which such certificate or
acceptance was issued, or from any batch of lake prepared with such
color additive, shall be considered to be from a batch that has not
been certified in accordance with the regulations in this part.
Whenever the Commissioner learns that any certificate or acceptance of
a notice claiming certification has been obtained through fraud or
material misrepresentation, the Commissioner shall notify the holder of
the certificate or acceptance that it is of no effect.
(b) If, between the time a sample of color additive accompanying a
request for certification or retained by a firm that has submitted a
notice claiming certification is taken from a batch of color additive
and the time a certificate or an acceptance of the notice claiming
certification for such batch is received by the person to whom such
certificate or acceptance is issued, any such color additive becomes
changed in composition, such certificate or such acceptance shall not
be effective with respect to such changed color additive, and such
changed color additive, and any lake prepared with such color additive,
shall be considered to be from a batch that has not been certified in
accordance with the regulations in this part.
(c) If, at any time after a certificate or an acceptance of a
notice claiming certification is received by the person to whom it is
issued, any color additive from the batch covered by such certificate
or acceptance becomes changed in composition, such certificate or
acceptance shall expire with respect to such changed color additive.
After such expiration, such color additive and any lake prepared with
such color additive shall be considered to be from a batch that has not
been certified in accordance with this part; except that such color
additive or lake shall not be so considered when used for coloring a
food, drug, or cosmetic, or for the purpose of certifying a batch of a
mixture in which such color additive was used as an ingredient, or for
use in preparing a batch of a mixture for which exemption from
certification has been authorized, or for use in preparing a batch of
lake for which certification is claimed under Sec. 80.31(b), if such
change resulted solely from such use.
(d) A certificate or an acceptance of a notice claiming
certification shall expire with respect to any color additive covered
thereby if the package in which such color additive was closed for
shipment or delivery is opened. After such expiration such color
additive shall be considered to be from a batch that has not been
certified, except that such color additive shall not be so considered
when the package is opened;
* * * * *
(h) When the listing or the specifications for a color additive are
revoked or amended, the final order effecting the revocation or
amendment may specify, in addition to its own effective date, a date on
which all previous certificates or acceptances of
[[Page 8415]]
notices claiming certification for existing batches and portions of
batches of such a color additive issued under the revoked or amended
regulations shall cease to be effective; and any such lots or batches
of the color additive, and any batches of lake prepared from such lots
or batches, shall be regarded as uncertified after the date specified
unless a new certificate or, for a lake, a new acceptance of a notice
claiming certification, can be and is obtained in conformance with the
new regulations. * * *
67. New Sec. 80.33 is added to subpart B to read as follows:
Sec. 80.33 Notice claiming certification for a batch of lake.
A notice claiming certification for a batch of lake or lake repack
shall:
(a) Be addressed to the Commissioner of Food and Drugs;
(b) Be prepared in the manner set forth in paragraph (i) of this
section;
(c) Be submitted in duplicate;
(d) Be signed by a responsible officer of the firm submitting the
notice. In the case of a foreign company, the notice must be signed by
a responsible officer of such firm, and by an agent of the firm who
resides in the United States;
(e) Show the name and place of business (street address, city,
State, and zip code) of the firm submitting the notice;
(f) Be accompanied by the fee prescribed in Sec. 80.10 unless the
firm has established an advanced deposit to be used for prepayment of
such fees. In no case shall the Commissioner consider a notice claiming
certification for a batch of lake or lake repack if the fee
accompanying such notice is less than that required by Sec. 80.10 or if
such fee exceeds the amount held in the advance deposit account of the
firm submitting such notice; and
(g) Be accompanied by any label or labeling intended to be used
with the batch.
(h) The name of a lake shall be the name derived in the manner
described in part 74 of this chapter.
(i) The form for submission of the notice shall be one of the
following, depending on whether the color additive is a new batch of
lake or a repack of a previously certified batch of lake:
(1) Notice claiming certification for a new batch of lake.
Date-------------------------------------------------------------------
Division of Programs and Enforcement Policy (HFS-105), Center for
Food Safety and Applied Nutrition, Food and Drug Administration, 200
C St. SW., Washington, DC 20204.
In accordance with the regulations promulgated under the Federal
Food, Drug, and Cosmetic Act, we hereby give notice that we claim
certification for a batch of lake.
Name of lake-----------------------------------------------------------
Batch number-----------------------------------------------------------
Batch weighs-----------------------------------------------------------
pounds (or kilograms)
Total color ______ percent of batch
For each straight color used:
Color content ______ percent of batch.
How stored pending certification---------------------------------------
----------------------------------------------------------------------
----------------------------------------------------------------------
(State conditions of storage, with kind and size of containers,
location, etc.)
For use in-------------------------------------------------------------
----------------------------------------------------------------------
----------------------------------------------------------------------
(State proposed uses)
Ingredients of batch
Name of each straight color used---------------------------------------
----------------------------------------------------------------------
For each straight color used:
Certified Lot number---------------------------------------------------
Quantity used ______ pounds (or kilograms)
For each precipitant or substratum ingredient used:
Name of ingredient used------------------------------------------------
Quantity used ______ pounds (or kilograms)
If any previously certified batches of lake have been used,
provide the following information for each such batch.
Name of lake-----------------------------------------------------------
FDA acceptance number
(or certified lot number)----------------------------------------------
Quantity used----------------------------------------------------------
pounds (or kilograms), Required fee, Sec. 30.00
(drawn to the order of Food and Drug Administration.)
This batch of lake was manufactured by the undersigned firm and
meets the requirements of 21 CFR parts 74 and 80. The records
required by 21 CFR 80.39, including a representative sample of the
batch, are available for FDA inspection at the undersigned firm.
(Signed)---------------------------------------------------------------
By---------------------------------------------------------------------
(Title)
(2) Notice claiming certification for a repack of a batch of
certified lake.
Date-------------------------------------------------------------------
Division of Programs and Enforcement Policy (HFS-105), Center for
Food Safety and Applied Nutrition, Food and Drug Administration, 200
C St. SW., Washington, DC 20204.
In accordance with the regulations promulgated under the Federal
Food, Drug, and Cosmetic Act, we hereby give notice that we claim
certification for a batch of lake repack.
Name of lake-----------------------------------------------------------
Original batch:
FDA acceptance number
(or certified lot number)----------------------------------------------
Total color ______ percent of batch
For each straight color used:
Color content ______ percent of batch.
This lake obtained from (provide name and place of business of
manufacturer of the lake)
Batch number-----------------------------------------------------------
Batch weighs ______ pounds
(or kilograms)
Repacked batch:
Total color ______ percent of batch
For each straight color used:
Color content ______ percent of batch.
How stored pending certification---------------------------------------
----------------------------------------------------------------------
----------------------------------------------------------------------
(State conditions of storage, with kind and size of containers,
location, etc.)
Certified for use in---------------------------------------------------
----------------------------------------------------------------------
----------------------------------------------------------------------
----------------------------------------------------------------------
(State proposed uses)
Required fee, $30.00 (drawn to the order of Food and Drug
Administration).
This batch of lake was repacked by the undersigned firm and
meets the requirements of 21 CFR parts 74 and 80. The records
required by 21 CFR 80.39, including a representative sample of the
batch, are available for FDA inspection at the undersigned firm.
(Signed)---------------------------------------------------------------
By---------------------------------------------------------------------
(j) The Food and Drug Administration will furnish a response to
each notifier within 5 working days of receipt of the notice. The
response will either:
(1) Accept the notice claiming certification; or
(2) Reject the notice claiming certification, in which case the
batch of lake covered by the notice has not complied with the
requirements of Sec. 80.31(b) of this chapter and is not a certified
batch.
Sec. 80.34 [Amended]
68. Section 80.34 Authority to refuse certification service is
amended in paragraph (a)(1) by removing the phrase ``a certificate''
and adding in its place the phrase ``a certificate or an acceptance of
a notice claiming certification''; and in paragraph (a)(4) by removing
the phrase ``color additives and intermediates'' and adding in its
place ``color additives, intermediates and substrata''.
Sec. 80.35 [Amended]
69. Section 80.35 Color additive mixtures; certification and
exemption from certification is amended in paragraphs (a) and (b) by
removing the words ``straight colors'' and adding in their place the
words ``listed colors''; and in paragraph (b) by removing the words
``straight color'' and adding in their place the words ``listed color''
the three times they appear.
70. Section 80.37 is revised to read as follows:
Sec. 80.37 Treatment of batch pending certification.
Immediately after the sample is taken that (for a batch of color
additive subject to certification under Sec. 80.31(a)) is to accompany
a request for certification of the batch or (for a batch of lake
subject to certification under Sec. 80.31(b)) is to be
[[Page 8416]]
retained by the firm preparing or repacking the batch, the batch shall
be:
(a) Stored in containers of such kind as to prevent change in
composition.
(b) Held under the control of the person requesting or claiming
certification until certified.
(c) Marked, by labeling or otherwise, in a manner such that there
can be no question as to the identity of the batch and no question that
it is not to be used until the requested certificate or acceptance of
the notice claiming certification has been issued.
71. Section 80.38 is revised to read as follows:
Sec. 80.38 Treatment of batch after certification.
(a) Labeling. (1) Immediately upon notification that a batch of
color additive has been certified under Sec. 80.31(a), the person
requesting certification thereof shall identify such batch, by
labeling, with the certified lot number.
(2) Immediately upon notification that the notice submitted in
accordance with Sec. 80.33 has been accepted, the firm claiming
certification for the batch shall identify such batch, by labeling,
with the FDA acceptance number.
(b) Storage. The person requesting or claiming certification shall
maintain storage in such manner as to prevent change in composition
until such batch has been packaged and labeled as required by
Secs. 70.20 and 70.25 of this chapter, except that the person
requesting or claiming certification may use such color additive for
the purpose of coloring a food, drug, or cosmetic.
72. Section 80.39 is revised to read as follows:
Sec. 80.39 Records.
(a) Records of distribution. (1) The person to whom a certificate
is issued or the firm to which FDA issues an acceptance of a notice
claiming certification shall keep complete records showing the disposal
of all the color additive from the batch covered by such certificate or
such acceptance. These records shall show:
(i) Each quantity used by such person or firm from such batch and
the date and kind of such use.
(ii) The date and quantity of each shipment or delivery from such
batch, and the name and post office address of the person to whom such
shipment or delivery was made.
(2) Upon the request of any officer or employee of the Food and
Drug Administration or of any other officer or employee acting on
behalf of the Secretary of Health and Human Services, such person or
such firm, at all reasonable hours until at least 2 years after
disposal of all such color additive, shall make the records required by
paragraph (a)(1) of this section available to any such officer or
employee, and shall accord to such officer or employee full opportunity
to make inventory of stocks of such color additive on hand and
otherwise to check the correctness of such records.
(b) Certification records for lakes. (1) The manufacturer or
repacker of a lake certified under Sec. 80.31(b) shall keep complete
records showing that the batch of lake covered by the notice claiming
certificaion is in compliance with parts 74 and 80 of this chapter.
(i) For both manufacturers and repackers, these records shall
include:
(A) A copy of the notice claiming certification for the batch;
(B) A copy of FDA's acceptance of the notice; and
(C) Complete reports of all chemical analyses performed on the
batch. Such analyses shall include, for each batch, analyses that
establish the percent total color for the batch and, if the batch
contains more than one straight color, the percent color for each
straight color in the batch.
(ii) For manufacturers only, the records shall also include:
(A) A copy of the certificate for each batch of straight color used
to prepare the batch of lake;
(B) For each certified batch of lake that was used as an
ingredient, a copy of FDA's acceptance of the notice claiming
certification for the batch, or if certified before (date of
publication of the final rule), a copy of the certificate for the
batch;
(C) Manufacturer specifications for substratum and precipitant
ingredients used in the preparation of the batch; and
(D) For each batch that contains a barium salt as provided in
Secs. 74.1050 and 74.2050 of this chapter, analyses that show that the
batch meets the specification for soluble barium in Sec. 74.1050(b) of
this chapter.
(2) A firm claiming certification for a batch of lake under
Sec. 80.31(b) shall retain an 8-ounce sample of the batch as required
by Sec. 80.22(b); however, such sample need not be submitted to FDA.
(3) Upon the request of any officer or employee of the Food and
Drug Administration or of any other officer or employee acting on
behalf of the Secretary of Health and Human Services, such firm, at all
reasonable hours until at least 2 years after disposal of all such
color additive, shall make the records and the sample required by
paragraphs (b)(1) through (b)(3) of this section available to any such
officer or employee, and shall accord to such officer or employee full
opportunity to make inventory of stocks of such color additive on hand
and otherwise to check the correctness of such records.
(c) The records required to be kept by paragraphs (a) and (b) of
this section shall be kept separately from all other records.
PART 81--GENERAL SPECIFICATIONS AND GENERAL RESTRICTIONS FOR
PROVISIONAL COLOR ADDITIVES FOR USE IN FOODS, DRUGS, AND COSMETICS
73. The authority citation for 21 CFR part 81 continues to read as
follows:
Authority: Secs. 701, 721 of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 371, 379e).
PART 81--[REMOVED]
74. Part 81 is removed.
PART 82--LISTING OF CERTIFIED PROVISIONALLY LISTED COLORS AND
SPECIFICATIONS
75. The authority citation for 21 CFR part 82 continues to read as
follows:
Authority: Secs. 701, 721 of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 371, 376, 379e).
PART 82--[REMOVED]
76. Part 82 is removed.
PART 101--FOOD LABELING
77. The authority citation for 21 CFR part 101 continues to read as
follows:
Authority: Secs. 4, 5, 6 of the Fair Packaging and Labeling Act
(15 U.S.C. 1453, 1454, 1455); secs. 201, 301, 402, 403, 409, 701 of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 342,
343, 348, 371).
78. Section 101.22 is amended in paragraph (k)(1) by revising the
first sentence and by removing the phrase ``or part 82'' in the second
sentence to read as follows:
Sec. 101.22 Foods; labeling of spices, flavorings, colorings and
chemical preservatives.
* * * * *
(k) * * *
(1) A color additive, including a lake, subject to certification
under section 721(c) of the act shall be declared by the name of the
color additive listed in the applicable regulation in part 74 of this
chapter, except that it is not necessary to include the ``FD&C'' prefix
or the term ``No.'' in the declaration, and for lakes it is also not
necessary to identify the aluminum cation or alumina substratum, but
the term ``Lake'' shall be
[[Page 8417]]
included in the declaration (e.g., Blue 1 Lake). * * *
* * * * *
PART 178--INDIRECT FOOD ADDITIVES; ADJUVANTS, PRODUCTION AIDS, AND
SANITIZERS
79. The authority citation for 21 CFR part 178 continues to read as
follows:
Authority: Secs. 201, 402, 409, 721 of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 321, 342, 348, 379e).
Sec. 178.3297 [Amended]
80. Section 178.3297 Colorants for polymers is amended in paragraph
(d) by removing the phrase ``, 81, and 82''.
PART 201--LABELING
81. The authority citation for 21 CFR part 201 continues to read as
follows:
Authority: 201, 301, 501, 502, 503, 505, 506, 507, 508, 510 512,
530-542, 701, 704, 721 of the Federal Food, Drug, and Cosmetic Act
(21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 357, 358, 360, 360b,
360gg-360ss, 371, 374, 379e); secs 215, 301, 351, 361 of the Public
Health Service Act (42 U.S.C. 216, 241, 262, 264).
Sec. 201.20 [Amended]
82. Section 201.20 Declaration of presence of FD&C Yellow No. 5
and/or FD&C Yellow No. 6 in certain drugs for human use is amended in
paragraph (a) by adding the words ``or a lake of FD&C Yellow No. 5''
before the words ``as a color additive using the names'', in paragraph
(b) by adding the words ``or a lake of FD&C Yellow No. 5'' before the
words ``that are administered'', and in paragraph (c) by adding the
words ``or a lake of FD&C Yellow No. 6'' before the words ``shall
specifically''.
PART 701--COSMETIC LABELING
83. The authority citation for 21 CFR part 701 continues to read as
follows:
Authority: Secs. 201, 502, 601, 602, 603, 701, 704 of the
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 352, 361, 362,
363, 371, 374); secs. 5, 6 of the Fair Packaging and Labeling Act
(15 U.S.C. 1454, 1455).
84. Section 701.3 is amended by redesignating paragraph (c)(1) as
paragraph (c)(1)(ii) and by adding new paragraph (c)(1)(i) to read as
follows:
Sec. 701.3 Designation of ingredients.
* * * * *
(c) * * *
(1)(i) For color additives, the name of the color additive listed
in the applicable regulation in part 73 or 74 of this chapter, except
that it is not necessary to include the ``FD&C'' or ``D&C'' prefix or
the term ``No.'' in the declaration, but the prefix ``Ext.'' shall be
included in the declaration. (For example, Ext. D&C Yellow No. 7 may be
declared as Ext. Yellow 7.) For lakes, it is also not necessary to
identify the cation precipitants or the substrata, but the term
``Lake'' shall be included in the declaration. (For example, the name
of a lake prepared by the extension of FD&C Red No. 40 and D&C Yellow
No. 10 on alumina and titanium dioxide using aluminum chloride and
calcium chloride precipitants is ``Red 40 and Yellow 10 Lake.'').
* * * * *
Dated: February 16, 1996.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 96-4584 Filed 2-29-96; 8:45 am]
BILLING CODE 4160-01-P
