Listing of Color Additives Subject to Certification; D&C Black No. 3, 33664-33667 [E7-11801]
Download as PDF
<![CDATA[
33664
Federal Register / Vol. 72, No. 117 / Tuesday, June 19, 2007 / Rules and Regulations
Paperwork Reduction Act
This final rule imposes no reporting/
recordkeeping requirements
necessitating clearance by OMB.
13. Mental Disorders (12.00 and 112.00):
July 1, 2008.
*
(Catalog of Federal Domestic Assistance
Program Nos. 96.001, Social SecurityDisability Insurance; 96.002, Social SecurityRetirement Insurance; 96.004, Social
Security-Survivors Insurance; 96.006,
Supplemental Security Income)
Administrative practice and
procedure, Blind, Disability benefits,
Old-Age, Survivors and Disability
Insurance, Reporting and recordkeeping
requirements, Social Security.
Dated: June 12, 2007.
Michael J. Astrue,
Commissioner of Social Security.
For the reasons set forth in the
preamble, part 404, subpart P, chapter
III of title 20 of the Code of Federal
Regulations is amended as set forth
below.
PART 404—FEDERAL OLD-AGE,
SURVIVORS AND DISABILITY
INSURANCE (1950— )
Subpart P—[Amended]
1. The authority citation for subpart P
of part 404 continues to read as follows:
I
Authority: Secs. 202, 205(a), (b), and (d)–
(h), 216(i), 221(a) and (i), 222(c), 223, 225,
and 702(a)(5) of the Social Security Act (42
U.S.C. 402, 405(a), (b), and (d)–(h), 416(i),
421(a) and (i), 422(c), 423, 425, and
902(a)(5)); sec. 211(b), Pub. L. 104–193, 110
Stat. 2105, 2189; sec. 202, Pub. L. 108–203,
118 Stat. 509 (42 U.S.C. 902 note).
2. Appendix 1 to subpart P of part 404
is amended by revising items 1, 4, 6, 8,
10, 12, 13, and 15 of the introductory
text before Part A to read as follows:
I
Appendix 1 to Subpart P of Part 404—
Listing of Impairments
*
*
*
1. Growth Impairment (100.00): July 1,
2008.
*
*
*
*
*
4. Respiratory System (3.00 and 103.00):
July 1, 2008.
*
*
*
*
*
6. Digestive System (5.00 and 105.00): July
1, 2008.
*
*
*
*
*
pwalker on PROD1PC71 with RULES
8. Hematological Disorders (7.00 and
107.00): July 1, 2008.
*
*
*
*
*
10. Endocrine System (9.00 and 109.00):
July 1, 2008.
*
*
*
*
*
12. Neurological (11.00 and 111.00): July 1,
2008.
VerDate Aug<31>2005
17:54 Jun 18, 2007
Jkt 211001
*
*
*
*
*
*
*
[FR Doc. E7–11752 Filed 6–18–07; 8:45 am]
BILLING CODE 4191–02–P
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
I
*
*
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
List of Subjects in 20 CFR Part 404
*
*
15. Immune System (14.00 and 114.00):
July 1, 2008.
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: https://
www.regulations.gov. Follow the
instructions for submitting comments.
• Agency Web site: https://
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
PO 00000
Frm 00028
Fmt 4700
Sfmt 4700
objections submitted to the agency by email. 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 https://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 https://
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 § 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
E:\FR\FM\19JNR1.SGM
19JNR1
Federal Register / Vol. 72, No. 117 / Tuesday, June 19, 2007 / Rules and Regulations
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°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
pwalker on PROD1PC71 with RULES
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 (§ 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
VerDate Aug<31>2005
17:54 Jun 18, 2007
Jkt 211001
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
PO 00000
Frm 00029
Fmt 4700
Sfmt 4700
33665
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
E:\FR\FM\19JNR1.SGM
19JNR1
33666
Federal Register / Vol. 72, No. 117 / Tuesday, June 19, 2007 / Rules and Regulations
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 additive1 (Ref. 4).
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).
pwalker on PROD1PC71 with RULES
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.
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).
VerDate Aug<31>2005
17:54 Jun 18, 2007
Jkt 211001
V. Inspection of Documents
In accordance with § 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 § 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
PO 00000
Frm 00030
Fmt 4700
Sfmt 4700
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.
I 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
1. The authority citation for 21 CFR
part 74 continues to read as follows:
I
Authority: 21 U.S.C. 321, 341, 342, 343,
348, 351, 352, 355, 361, 362, 371, 379e.
2. Section 74.2053 is added to subpart
C to read as follows:
I
§ 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°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:
E:\FR\FM\19JNR1.SGM
19JNR1
Federal Register / Vol. 72, No. 117 / Tuesday, June 19, 2007 / Rules and Regulations
(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 § 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 § 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
Food and Drug Administration
21 CFR Part 1271
[Docket No. 1997N–0484T]
Human Cells, Tissues, and Cellular and
Tissue-Based Products; Donor
Screening and Testing, and Related
Labeling
Food and Drug Administration,
HHS.
pwalker on PROD1PC71 with RULES
ACTION:
Final rule.
SUMMARY: The Food and Drug
Administration (FDA) is adopting as a
final rule, without change, the
provisions of the interim final rule that
amended certain regulations regarding
the screening and testing of donors of
human cells, tissues, and cellular and
tissue-based products (HCT/Ps), and
related labeling. FDA is taking this
action to complete the rulemaking
initiated with the interim final rule.
VerDate Aug<31>2005
17:54 Jun 18, 2007
Jkt 211001
This rule is effective June 19,
2007.
FOR FURTHER INFORMATION CONTACT:
Brenda R. Friend, Center for Biologics
Evaluation and Research (HFM–17),
Food and Drug Administration, 1401
Rockville Pike, suite 200N, Rockville,
MD 20852–1448, 301–827–6210.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of May 25,
2005 (70 FR 29949), FDA issued an
interim final rule on Human Cells,
Tissues, and Cellular and Tissue-Based
Products; Donor Screening and Testing,
and Related Labeling (hereinafter
referred to as the interim final rule).
These regulations became effective upon
the date of publication in the Federal
Register. We issued the interim rule to
assure that the changes became effective
concurrently with the Eligibility
Determination for Donors of Human
Cells, Tissues, and Cellular and TissueBased Products final rule (69 FR 29786,
May 25, 2004) and the Current Good
Tissue Practice for Human Cell, Tissue,
and Cellular and Tissue-Based Product
Establishments; Inspection and
Enforcement final rule (69 FR 68612,
November 24, 2004) on May 25, 2005.
In this way, establishments were not
required to take steps to comply with
the provisions in part 1271 (21 CFR part
1271) that were replaced by the changes
set out in the interim final rule, and
certain HCT/Ps would continue to be
available.
II. Comments on the Interim Final Rule
and FDA Responses
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
AGENCY:
DATES:
We received several comments on the
interim final rule. To make it easier to
identify comments and our responses,
the word ‘‘Comment,’’ in parentheses,
will appear before the comment’s
description, and the word ‘‘Response,’’
in parentheses, will appear before our
response. We have also numbered each
comment to help distinguish between
different comments. The number
assigned to each comment is purely for
organizational purposes and does not
signify the comment’s value or
importance or the order in which it was
received.
(Comment 1) A comment appreciated
and applauded the change to
§ 1271.370(b)(4) to allow labeling with
warning(s) to accompany the HCT/P
when the HCT/P container is too small
to accommodate the warning(s) on the
label. Another comment expressed
concern that the accompanying labeling
could be ignored or lost.
(Response) We acknowledge and
appreciate the supportive comment.
PO 00000
Frm 00031
Fmt 4700
Sfmt 4700
33667
This requirement addresses the
situation where it is not physically
possible to include warnings directly on
the HCT/P label, either because the
container is too small or the HCT/P is
cryopreserved, which may interfere
with adherence of label materials. In
these situations, the warnings must
accompany the HCT/P.
We acknowledge the comment’s
concern that it is better to provide
information on the HCT/P’s label.
However, we permit other important
information, such as the summary of
records, to accompany the HCT/P; such
important information is not present on
the HCT/P label. We believe that
consignees are generally careful to make
sure information accompanying HCT/Ps
is not ignored or lost, and we believe
that the accompanying information will
be available. Necessity compels this
authorization for certain information to
accompany an HCT/P when it is not
possible to include it on the label, and
we conclude that it is adequate to
provide such information in
accompanying documents when it is
necessary to do so.
(Comment 2) A comment noted that
§ 1271.55(a)(1) requirements (i.e.,
affixing a distinct identification code to
the HCT/P container) were clearly
designed to maintain donor anonymity.
However, the comment asked if fertility
clinics could write in information about
the recipient (e.g., name, account
number) because by the time a donor’s
HCT/P is collected, a specific recipient
has already been identified. The
comment stated that fertility clinics, for
example, never collect anonymously
donated oocytes without already having
a recipient identified and ready to
receive the donation.
(Response) The requirements in
§ 1271.55(a)(1) are focused on protecting
the identity of the donor in the interest
of confidentiality. We note that this
provision prescribes how an
establishment must label the HCT/P
before releasing it for distribution, but
does not prohibit the addition of the
recipient’s name once the donor
eligibility determination is completed
and the reproductive HCT/P is released
for distribution. For an oocyte donation,
the release determination is likely to be
completed very soon after collection.
(Comment 3) A few comments
suggested changes to the timing of the
specimen collection in § 1271.80(b). In
particular, a comment noted that
§ 1271.80(b)(1) permits testing on oocyte
donors up to 30 days before recovery,
while § 1271.80 seems to maintain a 7day testing window for semen donors,
whose spermatozoa will combine with
the oocytes to create an embryo for a
E:\FR\FM\19JNR1.SGM
19JNR1
]]>Agencies
[Federal Register Volume 72, Number 117 (Tuesday, June 19, 2007)]
[Rules and Regulations]
[Pages 33664-33667]
From the Federal Register Online via the Government Printing 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: https://www.regulations.gov.
Follow the instructions for submitting comments.
Agency Web site: https://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 https://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 https://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
