[Federal Register Volume 72, Number 117 (Tuesday, June 19, 2007)]
[Rules and Regulations]
[Pages 33664-33667]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-11801]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 74
[Docket No. 1995C-0286 (formerly Docket No. 95C-0286)]
Listing of Color Additives Subject to Certification; D&C Black
No. 3
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is amending the color
additive regulations to provide for the safe use of D&C Black No. 3
(bone black, subject to FDA batch certification) as a color additive in
eyeliner, eye shadow, mascara, and face powder. This action is in
response to a petition filed by Ebonex Corp.
DATES: This rule is effective July 20, 2007. Submit written or
electronic objections and requests for a hearing by July 19, 2007. See
section VIII of the SUPPLEMENTARY INFORMATION section of this document
for information on the filing of objections.
ADDRESSES: You may submit written or electronic objections and requests
for a hearing, identified by Docket No 1995C-0286, by any of the
following methods:
Electronic Submissions
Submit electronic objections in the following ways:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Agency Web site: http://www.fda.gov/dockets/ecomments.
Follow the instructions for submitting comments on the agency Web site.
Written Submissions
Submit written objections in the following ways:
FAX: 301-827-6870.
Mail/Hand delivery/Courier [For paper, disk, or CD-ROM
submissions]: Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
To ensure more timely processing of objections, FDA is no longer
accepting objections submitted to the agency by e-mail. FDA encourages
you to continue to submit electronic objections by using the Federal
eRulemaking Portal or the agency Web site, as described in the
Electronic Submissions portion of this paragraph.
Instructions: All submissions received must include the agency name
and docket number for this rulemaking. All objections received will be
posted without change to http://www.fda.gov/ohrms/dockets/default.htm,
including any personal information provided. For detailed instructions
on submitting objections, see the ``Objections'' heading of the
SUPPLEMENTARY INFORMATION section of this document.
Docket: For access to the docket to read background documents or
objections received, go to http://www.fda.gov/ohrms/dockets/default.htm
and insert the docket number, found in brackets in the heading of this
document, into the ``Search'' box and follow the prompts and/or go to
the Division of Dockets Management, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Judith Kidwell, Center for Food Safety
and Applied Nutrition (HFS-265), Food and Drug Administration, 5100
Paint Branch Pkwy., College Park, MD 20740, 301-436-1071.
SUPPLEMENTARY INFORMATION:
I. Background
In a notice published in the Federal Register of September 1, 1995
(60 FR 45724), FDA announced that a color additive petition (CAP
5C0247) had been filed by the Ebonex Corp., P.O. Box 3247, Melvindale,
MI 48122. The petition proposed to amend the color additive regulations
to provide for the safe use of bone black as a color additive in
cosmetics, including cosmetics intended for use in the eye area. The
petitioner subsequently narrowed the proposed uses of bone black to
eyeliner, eye shadow, mascara, and face powder.
During its review of the petition, the agency determined that the
color additive, bone black, will require batch certification by FDA.
The agency intends to give each certified batch of the subject color
additive the name D&C Black No. 3. Therefore, this color additive will
be identified as D&C Black No. 3.
The requested use of D&C Black No. 3 includes cosmetics for use in
the area of the eye. The term ``area of the eye'' is defined in Sec.
70.3(s) (21 CFR 70.3(s)) as ``the area enclosed within the
circumference of the supra-orbital ridge and the infra-orbital ridge,
including the
[[Page 33665]]
eyebrow, the skin below the eyebrow, the eyelids and the eyelashes, and
conjunctival sac of the eye, the eyeball, and the soft areolar tissue
that lies within the perimeter of the infra-orbital ridge.''
Section 70.5(a) (21 CFR 70.5(a)) states that ``No listing or
certification of a color additive shall be considered to authorize the
use of any such color additive in any article intended for use in the
area of the eye unless such listing or certification of such color
additive specifically provides for such use.''
II. Identity and Specifications
D&C Black No. 3 is a black pigment made from calcined cattle bones.
The bones are heated twice to temperatures in excess of 700[deg]C for
at least 6 hours each time. The twice burned char is then washed. The
carbon content is approximately 8 percent to 10 percent and most of the
remaining composition is tricalcium phosphate (as calcium
hydroxyapatite).
As explained under section III.B of this document, D&C Black No. 3
may contain low levels of potentially carcinogenic polycyclic aromatic
hydrocarbon (PAH) impurities. To limit the amounts of these impurities
in the color additive, FDA is setting a specification for total PAHs
and is requiring that D&C Black No. 3 be from a batch of bone black
certified by FDA.
To limit the amounts of heavy metals in the color additive, which
may be derived from the source of the color and the manufacturing
process, the agency also is setting specifications for arsenic and
lead. To ensure purity of the color additive, the agency also is
setting specifications for carbon, calcium hydroxyapatite, moisture,
and silica. To be used lawfully in cosmetics in the United States, all
batches of bone black must meet the specifications identified in the
regulation.
III. Safety Evaluation
A. Determination of Safety
Under section 721(b)(4) of the Federal Food, Drug, and Cosmetic Act
(the act) (21 U.S.C. 379e(b)(4)), the ``general safety standard'' for
color additives, a color additive cannot be listed for a particular use
unless a fair evaluation of the data and information available to FDA
establishes that the color additive is safe for that use. FDA's color
additive regulations (Sec. 70.3(i)) define safe as ``convincing
evidence that establishes with reasonable certainty that no harm will
result from the intended use of the color additive.''
The anticancer clause of the color additive amendments (section
721(b)(5)(B) of the act), also known as the Delaney clause) provides
that for any use of a color additive which will or may result in
ingestion of all or part of such additive, the color additive shall be
deemed to be unsafe and shall not be listed if the additive is found to
induce cancer when ingested by man or animal, or if it is found, after
tests which are appropriate for the evaluation of the safety of
additives for use in food, to induce cancer in man or animal (section
721(b)(5)(B)(i) of the act). Further, under section 721(b)(5)(B)(ii) of
the act, for any use of a color additive which will not result in
ingestion of any part of such additive, the color additive shall be
deemed to be unsafe and shall not be listed if, after tests which are
appropriate for the evaluation of the safety of additives for such use,
or after other relevant exposure of man or animal to such additive, it
is found to induce cancer in man or animal.
Importantly, however, the Delaney clause applies to the additive
itself and not to impurities in the additive. That is, where an
additive itself has not been shown to cause cancer, but contains a
carcinogenic impurity, the additive is properly evaluated under the
general safety standard using risk assessment procedures to determine
whether there is a reasonable certainty that no harm will result from
the intended use of the additive (Scott v.FDA, 728 F.2d 322 (6th Cir.
1984)).
B. Safety of Petitioned Use of the Additive
Because D&C Black No. 3 is made from cattle bones, one potential
safety concern is the risk from using cattle materials in the
preparation of bone black that could be infected with the agent that
causes Bovine Spongiform Encephalopathy (BSE). To address the potential
risk of BSE, FDA prohibits the use of certain cattle materials in human
food and cosmetics. FDA also requires that manufacturers and processors
of human food and cosmetics that are manufactured from, processed with,
or otherwise contain, material from cattle establish and maintain
records sufficient to demonstrate that the human food or cosmetic is
not manufactured from, processed with, or does not otherwise contain,
prohibited cattle materials (21 CFR 189.5 and 700.27). FDA's regulatory
measures to prevent BSE contamination of U.S. food and cosmetics ensure
that cattle materials that carry the highest risk of transmitting the
agent that causes BSE are excluded from being used as a source to
produce D&C Black No. 3 for use in cosmetics. Therefore, FDA concludes
that D&C Black No. 3 prepared in compliance with these measures is safe
with respect to the potential concern from using cattle materials.
Toxicity studies provided by the petitioner, including a dermal
irritation study, an ocular irritation study, a delayed-contact
hypersensitivity study, and a bioavailability study, demonstrate the
color additive itself is safe for the proposed cosmetic uses. However,
the color additive has been shown to contain several impurities in
trace amounts, including carcinogenic PAHs. To minimize exposure to PAH
impurities, the agency is setting a limit for total PAHs in D&C Black
No. 3 of not more than 5 milligrams (mg)/kilogram (kg) (5 parts per
million). As discussed in the next three paragraphs, the limit for
total PAHs for D&C Black No. 3 will provide a reasonable certainty that
no harm will result from the intended use of the color additive.
Current data have shown that benzo(a)pyrene (B[a]P) is one of the
most potent carcinogens of the PAH family. To assess the risk from
exposure to PAHs, FDA used toxic equivalency factors (TEFs) to express
the comparative toxicity of individual PAHs as fractions of the
toxicity of B[a]P. This approach expresses the amount of PAHs present
in terms of B[a]P equivalents and estimates the risk for a mixture of
PAHs as if it were comprised of one chemical compound. Under this
methodology, B[a]P was assigned a TEF of 1. In estimating the exposure
of B[a]P equivalents from the petitioned uses of the color additive,
FDA normalized the residue levels of the individual PAHs to yield a
total PAH concentration of approximately 5 mg/kg (the limit for total
PAHs set by the regulation). Multiplying the normalized residue level
for each PAH by the TEF for that PAH and summing the results yields a
B[a]P-equivalent PAH concentration of approximately 1.2 mg/kg. Data
from a bioavailability study presented in the petition show that B[a]P
is not absorbed in appreciable amounts from cosmetic matrices (4
percent to 6 percent absorption) (Refs. 1 and 2). However, as a
conservative assumption based on the chemical composition of the
additive, the agency concluded that up to 50 percent of the total PAHs
were likely to be extracted from the additive under typical use
conditions, and thus available for absorption by the body (i.e., not
bound to the cosmetic formulation).
The agency used data from a carcinogenesis bioassay on B[a]P (Ref.
3), to estimate the upper-bound limit of lifetime human risk from
exposure to B[a]P equivalents resulting from the
[[Page 33666]]
petitioned uses of the color additive. This bioassay reported
treatment-related benign forestomach tumors or esophageal tumors in
male rats exposed to B[a]P. Using a linear-at-low-dose extrapolation
method and tumor incidence data from the bioassay, FDA estimated the
carcinogenic unit risk for B[a]P to be 1.75 (mg/kg body weight/
day)-1. Using this unit risk and an estimated daily exposure
of 5 x 10-8 mg of B[a]P equivalents/kg body weight/day, FDA
estimates the upper-bound lifetime human risk from the petitioned uses
of the color additive to be 8.8 x 10-8 (Ref. 1).
Because conservative assumptions were used to estimate exposure, an
individual's actual exposure to PAHs is expected to be substantially
less than the estimated exposure. The agency concludes that there is
reasonable certainty that no harm from exposure to PAHs would result
from the petitioned use of the color additive\1\ (Ref. 4).
---------------------------------------------------------------------------
\1\ FDA also estimated the upper-bound lifetime risk to PAHs
using the worst-case assumption that PAHs are present at the maximum
allowable limit of 5 mg/kg, and that all PAHs present have
carcinogenic potency equivalent to B[a]P. Based on this very
conservative approach, the upper-bound limit of lifetime human risk
from the petitioned uses of the additive is 3.7 x 10-7
(Ref. 1).
---------------------------------------------------------------------------
The agency also considered the potential risk from benzaldehyde,
benzonitrile, biphenyl, isoquinoline, pyridine and quinoline, which are
additional impurities produced in trace amounts in the color additive
from the manufacturing process. The agency concludes that none of these
substances is present in the color additive at levels that raise any
safety concerns, and that no specifications are necessary to control
the amount of these substances as impurities in the color additive
(Ref. 4).
IV. Conclusions
Based on data in the petition and other relevant considerations
discussed previously, FDA concludes that there is a reasonable
certainty that no harm will result from the petitioned use of D&C Black
No. 3 as a color additive in eyeliner, eye shadow, mascara, and face
powder. The agency also concludes that the color additive will achieve
its intended technical effect, and thus, is suitable for this use. The
agency further concludes that, in accordance with 21 CFR 71.20(b),
batch certification of D&C Black No. 3 is necessary to protect the
public health because of the need to limit the level of PAH impurities,
some of which have been shown to be carcinogenic. Therefore, 21 CFR
part 74 should be amended as set forth in this document.
V. Inspection of Documents
In accordance with Sec. 71.15 (21 CFR 71.15), the petition and the
documents that FDA considered and relied upon in reaching its decision
to approve the petition will be made available for inspection at the
Center for Food Safety and Applied Nutrition by appointment with the
information contact person (see FOR FURTHER INFORMATION CONTACT). As
provided in Sec. 71.15, the agency will delete from the documents any
materials that are not available for public disclosure before making
the documents available for inspection.
VI. Environmental Impact
The agency has carefully considered the potential environmental
effects of this action. FDA has concluded that the action will not have
a significant impact on the human environment, and that an
environmental impact statement is not required. The agency's finding of
no significant impact and the evidence supporting that finding,
contained in an environmental assessment, may be seen in the Division
of Dockets Management (see ADDRESSES) between 9 a.m. and 4 p.m., Monday
through Friday.
VII. Paperwork Reduction Act of 1995
This final rule contains no collection of information. Therefore,
clearance by the Office of Management and Budget under the Paperwork
Reduction Act of 1995 is not required.
VIII. Objections
This rule is effective as shown in the ``DATES'' section of this
document; except as to any provisions that may be stayed by the filing
of proper objections. Any person who will be adversely affected by this
regulation may file with the Division of Dockets Management (see
ADDRESSES) written or electronic objections. Each objection shall be
separately numbered, and each numbered objection shall specify with
particularity the provisions of the regulation to which objection is
made and the grounds for the objection. Each numbered objection on
which a hearing is requested shall specifically so state. Failure to
request a hearing for any particular objection shall constitute a
waiver of the right to a hearing on that objection. Each numbered
objection for which a hearing is requested shall include a detailed
description and analysis of the specific factual information intended
to be presented in support of the objection in the event that a hearing
is held. Failure to include such a description and analysis for any
particular objection shall constitute a waiver of the right to a
hearing on the objection. Three copies of all documents are to be
submitted and are to be identified with the docket number found in
brackets in the heading of this document. Any objections received in
response to the regulation may be seen in the Division of Dockets
Management between 9 a.m. and 4 p.m., Monday through Friday. FDA will
publish notice of the objections that the agency has received or lack
thereof in the Federal Register.
IX. References
The following references have been placed on display in the
Division of Dockets Management (see ADDRESSES) and may be seen by
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
1. Memorandum from Folmer, Division of Petition Review,
Chemistry Review Team, to Kidwell, Division of Petition Review, July
6, 2005.
2. Memorandum from Yourick, Cosmetics Toxicology Branch,
Division of Cosmetics and Compliance, to Kidwell, Division of
Petition Review, May 13, 2005.
3. Brune, H., R.P. Deutsch-Wenzel, M. Habs, et al.,
``Investigation of the Tumorigenic Response to Benzo[a]pyrene in
Aqueous Caffeine Solution Applied Orally to Sprague-Dawley Rats,''
Journal of Cancer Research and Clinical Oncology, 102:153-157, 1981.
4. Memorandum from Carlson, Division of Petition Review,
Toxicology Review Group I, to Kidwell, Division of Petition Review,
February 15, 2006.
List of Subjects in 21 CFR Part 74
Color additives, Cosmetics, Drugs.
0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
74 is amended as follows:
PART 74--LISTING OF COLOR ADDITIVES SUBJECT TO CERTIFICATION
0
1. The authority citation for 21 CFR part 74 continues to read as
follows:
Authority: 21 U.S.C. 321, 341, 342, 343, 348, 351, 352, 355,
361, 362, 371, 379e.
0
2. Section 74.2053 is added to subpart C to read as follows:
Sec. 74.2053 D&C Black No. 3.
(a) Identity. The color additive D&C Black No. 3 is a washed bone
char prepared from calcined cattle bones. The bones are twice heated in
excess of 700[deg]C for at least 6 hours.
(b) Specifications. D&C Black No. 3 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 practices:
[[Page 33667]]
(1) Calcium hydroxyapatite (CaO and P2O5),
not less than 75 percent and not more than 84 percent;
(2) Elemental carbon, not less than 7 percent;
(3) Moisture, not more than 7 percent;
(4) Silica (SiO2), not more than 5 percent;
(5) Arsenic, not more than 3 milligrams (mg)/kilogram (kg) (3 parts
per million (ppm));
(6) Lead, not more than 10 mg/kg (10 ppm); and
(7) Total polycyclic aromatic hydrocarbons (PAHs), not more than 5
mg/kg (5 ppm).
(c) Uses and restrictions. Cosmetics containing D&C Black No. 3
must comply with Sec. 700.27 of this chapter with respect to
prohibited cattle materials in cosmetic products. D&C Black No. 3 may
be safely used for coloring the following cosmetics in amounts
consistent with current good manufacturing practice: Eyeliner, eye
shadow, mascara, and face powder.
(d) Labeling. The label of the color additive shall conform to the
requirements of Sec. 70.25 of this chapter.
(e) Certification. All batches of D&C Black No. 3 shall be
certified in accordance with regulations in part 80 of this chapter.
Dated: June 11, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-11801 Filed 6-18-07; 8:45 am]
BILLING CODE 4160-01-S