[Federal Register Volume 83, Number 211 (Wednesday, October 31, 2018)]
[Rules and Regulations]
[Pages 54665-54674]
[FR Doc No: 2018-23725]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 73

[Docket No. FDA-2017-C-1951]

Termination of Listing of Color Additive Exempt From
Certification; Lead Acetate

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA or we) is amending the
color additive regulations to no longer provide for the use of lead
acetate in cosmetics intended for coloring hair on the scalp because
new data available since lead acetate was permanently listed
demonstrate that there is no longer a reasonable certainty of no harm
from the use of this color additive. This action is in response to a
color additive petition filed by the Environmental Defense Fund,
Earthjustice, Environmental Working Group, Center for Environmental
Health, Healthy Homes Collaborative, Health Justice Project of Loyola
University Chicago School of Law, Breast Cancer Fund, Improving Kids'
Environment, Consumers Union, Natural Resources Defense Council,
Consumer Federation of America, Learning Disabilities Association,
Maricel Maffini, and Howard Mielke.

DATES: This rule is effective December 3, 2018. See section XIII for
further information on the filing of objections. Submit either
electronic or written objections and requests for a hearing on the
final rule by November 30, 2018.

ADDRESSES: You may submit objections and requests for a hearing as
follows. Please note that late, untimely filed objections will not be
considered. Electronic objections must be submitted on or before
November 30, 2018. The https://www.regulations.gov electronic filing
system will accept comments until 11:59 p.m. Eastern Time at the end of
November 30, 2018. Objections received by mail/hand delivery/courier
(for written/paper submissions) will be considered timely if they are
postmarked or the delivery service acceptance receipt is on or before
that date.

Electronic Submissions

    Submit electronic objections in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Objections submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your objection will be
made public, you are solely responsible for ensuring that your
objection does not include any confidential information that you or a
third party may not wish to be posted, such as medical information,
your or anyone else's Social Security number, or confidential business
information, such as a manufacturing process. Please note that if you
include your name, contact information, or other information that
identifies you in the body of your objection, that information will be
posted on https://www.regulations.gov.
     If you want to submit an objection with confidential
information that you do not wish to be made available to the

public, submit the objection as a written/paper submission and in the
manner detailed (see ``Written/Paper Submissions'' and
``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper objections submitted to the Dockets
Management Staff, FDA will post your objection, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No.
FDA-2017-C-1951 for ``Termination of Listing of Color Additive Exempt
From Certification; Lead Acetate.'' Received objections, those filed in
a timely manner (see ADDRESSES), will be placed in the docket and,
except for those submitted as ``Confidential Submissions,'' publicly
viewable at https://www.regulations.gov or at the Dockets Management
Staff between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit an objection with
confidential information that you do not wish to be made publicly
available, submit your objections only as a written/paper submission.
You should submit two copies total. One copy will include the
information you claim to be confidential with a heading or cover note
that states ``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' We
will review this copy, including the claimed confidential information,
in our consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov 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 Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Molly A. Harry, Center for Food Safety
and Applied Nutrition, Food and Drug Administration, 5001 Campus Dr.,
College Park, MD 20740-3835,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

I. Introduction

    In the Federal Register of April 4, 2017 (82 FR 16321), FDA
announced that we filed a color additive petition (CAP 7C0309) (the
petition) submitted by the Environmental Defense Fund, Earthjustice,
Environmental Working Group, Center for Environmental Health, Healthy
Homes Collaborative, Health Justice Project of Loyola University
Chicago School of Law, Breast Cancer Fund, Improving Kids' Environment,
Consumers Union, Natural Resources Defense Council, Consumer Federation
of America, Learning Disabilities Association, Maricel Maffini, and
Howard Mielke (petitioners), c/o Mr. Tom Neltner, 1875 Connecticut Ave.
NW, Suite 600, Washington, DC 20009. The petition requested that we
repeal the regulation at Sec.  73.2396 (21 CFR 73.2396) to no longer
provide for the safe use of lead acetate in cosmetics intended for
coloring hair on the scalp. The notice of petition gave interested
parties until June 5, 2017, to submit comments on the filed color
additive petition.

II. Background and Regulatory History of Lead Acetate as a Color
Additive

    The color additive lead acetate (the trihydrate of lead (2+) salt
of acetic acid; CAS No. 6080-56-4) has been in use in cosmetic hair
dyes for many years. Under the provisions of the Color Additive
Amendments of 1960 to the Federal Food, Drug, and Cosmetic Act (FD&C
Act), FDA published a notice on December 10, 1963 (28 FR 13374),
stating that metallic salts (including lead acetate) used as hair
colorings are color additives within the meaning of the FD&C Act.
Because metallic salts, including lead acetate, were in use as color
components in hair dye prior to the Color Additive Amendments of 1960,
they were provisionally listed for this use on an interim basis under
the transitional provisions of the Color Additive Amendments (38 FR
7006, March 15, 1973). Subsequently, FDA gave interested persons until
July 30, 1973, to submit petitions proposing appropriate permanent
listings of any metallic salts as coloring components of hair dye not
presently listed for such use (38 FR 2996, January 31, 1973). On May
18, 1973, FDA received a color additive petition (CAP 3C0107) from the
Committee of the Progressive Hair Dye Industry requesting the permanent
listing of lead acetate as a color additive in cosmetic hair dyes. FDA
published a notice of filing of the petition in the Federal Register of
June 29, 1973 (38 FR 17260). While the petition was under review, FDA
added lead acetate to the codified provisional list for use as a color
component in hair dye on March 13, 1974 (39 FR 9657), with a closing
date of December 31, 1974. The closing date for the provisional listing
of lead acetate was postponed periodically pending the performance,
completion, and evaluation of toxicological and absorption studies. A
final rule in the Federal Register of March 3, 1978 (43 FR 8790),
details each postponement up to that time, and subsequent postponements
of the closing date for the provisional listing of lead acetate were
published in the Federal Register on January 2, 1979 (44 FR 45), March
6, 1979 (44 FR 12169), August 31, 1979 (44 FR 51216), February 22, 1980
(45 FR 11799), June 24, 1980 (45 FR 42255), and December 30, 1980 (45
FR 85725).
    In evaluating the scientific data submitted in CAP 3C0107, FDA
determined that the following issues required resolution to enable FDA
to evaluate the petition and determine the conditions of safe use of
lead acetate: (1) Whether absorption and systemic distribution of lead
acetate from hair dyes would occur, because the available scientific
data did not establish conclusively that lead acetate from hair dyes
was transdermally absorbed through the scalp; (2) whether lead acetate
is carcinogenic in humans, because it had been established through
animal feeding studies that lead is a carcinogen in rats and mice; (3)
whether the human epidemiological data available are equivocal; and (4)
which of the ``Delaney'' anticancer clauses in section 721(b)(5)(B) of
the FD&C Act (21 U.S.C. 379e(b)(5)(B)) is applicable to this use of
lead acetate (45 FR 72112, October 31, 1980).
    To resolve the issue of whether lead acetate would be transdermally
absorbed through the scalp, FDA requested that the petitioner perform a

definitive percutaneous absorption study (42 FR 62497 at 62499,
December 13, 1977). Results from a 1978 radioactive tracer skin lead
absorption study, using human volunteers, was submitted by the
petitioner of CAP 3C0107 for FDA review and later published by Moore et
al. (Ref. 1). The results of the percutaneous absorption study showed
that lead acetate in hair dye is absorbed through human skin and that
users who apply the hair dye as often as twice per week have an
estimated average daily lead absorption of 0.3 microgram ([micro]g).
FDA considered the absorbed amount of lead acetate from hair dye to be
``miniscule'' when compared to the average person's blood lead level
from background sources and concluded that the resulting increase in
exposure would have no discernible increase on the steady-state blood
lead level reported to be approximately 17 [micro]g per deciliter
([micro]g/dL) (45 FR 72112 at 72114).
    FDA also considered the applicability of the Delaney Clause
(section 721(b)(5)(B) of the FD&C Act) in determining whether lead
acetate could be permanently listed, considering the evidence that lead
was shown to be a carcinogen in animal feeding studies. The Delaney
Clause consists of two parts. The first part (section 721(b)(5)(B)(i)
of the FD&C Act) pertains specifically to ingested color additives. The
second part (section 721(b)(5)(B)(ii) of the FD&C Act) applies to non-
ingested color additives. FDA explained in the 1980 final rule that
because the first part of the Delaney Clause (section 721(b)(5)(B)(i)
of the FD&C Act) is limited to uses that will or may result in
ingestion, it does not apply to the use of lead acetate in hair dye
applied on the scalp. FDA then considered the applicability of the non-
ingestion clause, which states that a color additive shall be deemed
unsafe, and shall not be listed, for any use that will not result in
ingestion or any part of such additive, if evaluation of the safety of
additives for such use or after other relevant exposure of man or
animal to such additive, it is found by the Secretary of Health and
Human Services (Secretary) to induce cancer in man or animal. After
evaluation of the available relevant scientific evidence, FDA concluded
that the available animal feeding studies were not relevant to the use
of lead acetate in hair dye. FDA also concluded that the scientific
data submitted were not sufficient to substantiate a direct correlation
between dermal exposure to lead and human carcinogenicity.
Additionally, FDA considered two carcinogenicity risk assessments based
on the percutaneous absorption data submitted in the CAP, one prepared
by Dr. Richard Wilson of Harvard University (on behalf of the
petitioner of CAP 3C0107) and the other prepared by FDA personnel,
which concluded a 1:18 million and 1:12 million chance of developing
cancer, respectively, by using lead acetate containing hair dye. FDA
determined that these assessments supported the conclusion that any
carcinogenic risk likely to result from use of lead acetate-containing
hair dye could not be considered significant in terms of public health
protection (45 FR 72112 at 72116).
    Based on the evaluation of the available data, FDA concluded that
lead acetate was safe for use in hair dyes intended for use on the
scalp. On October 31, 1980, FDA approved the petition and permanently
listed lead acetate in Sec.  73.2396 as a color additive for the safe
use in cosmetics for coloring hair on the scalp at levels up to 0.6
percent (weight to volume) lead, subject to certain restrictions and
labeling requirements (45 FR 72112). As a condition of safe use, the
regulation in Sec.  73.2396 specifies that lead acetate hair dye must
contain a cautionary statement.

III. Regulation of Color Additives

    The FD&C Act provides a process through which any person who wishes
to use a color additive in or on food, drugs, devices, or cosmetics,
may submit a petition proposing the issuance of a color additive
regulation listing such use with supporting information. A color
additive petition also may be submitted to propose the amendment or
repeal of any existing color additive regulation (see section
721(b)(5)(C) and (d) of the FD&C Act). In response to a color additive
petition, FDA may issue a regulation listing a color additive for use
in or on food, drugs, devices, or cosmetics only if it determines that
the additive is suitable and safe for such use (see section
721(b)(2)(A) of the FD&C Act). FDA's determination that a color
additive is safe means that there is convincing evidence that
establishes with reasonable certainty that no harm will result from the
intended condition of use of the color additive (21 CFR 170.3(i)). This
is referred to as the ``general safety clause'' for color additives. In
addition, the Delaney Clause, under section 721(b)(5)(B)(i) of the FD&C
Act, states that a color additive shall be deemed unsafe for any use
that will or may result in ingestion of all or part of such additive,
if the additive is found by the Secretary to induce cancer when
ingested by man or animal, or if it is found by the Secretary, after
tests that are appropriate for the evaluation of the safety of
additives for use in food, to induce cancer in man or animal. To
determine whether a color additive is safe under the general safety
clause, the FD&C Act requires FDA to consider, among other relevant
factors: (1) Probable consumption of, or other relevant exposure from,
the additive and of any substance formed in or on food, drugs or
devices, or cosmetics because of the use of the additive; (2)
cumulative effect, if any, of such additive ``in the diet of man or
animals,'' taking into account the same or any chemically or
pharmacologically related substance or substances in such diet; and (3)
safety factors recognized by experts ``as appropriate for the use of
animal experimentation data'' (see section 721(b)(5)(A) of the FD&C
Act). For FDA to grant a petition that seeks repeal of a color additive
regulation based upon new data concerning the safety of the color
additive, such data must be adequate for FDA to conclude that there is
no longer a reasonable certainty of no harm for the intended use of the
color additive or that it must be deemed unsafe under the Delaney
Clause.

IV. Petitioners' Argument for Repeal of Sec.  73.2396

    In accordance with the procedure in section 721(d) of the FD&C Act
for the issuance, amendment or repeal of regulations, the current color
additive petition (CAP 7C0309) requests that FDA repeal the regulation
for lead acetate in Sec.  73.2396. The petitioners assert the following
in support of their proposal (the petition, at pages 5 through 15):
    1. ``Toxicological evidence since 1980 shows there is no safe level
of exposure to lead compounds,'' and the ``scientific evidence
substantiating a direct correlation between lead exposure and human
carcinogenicity is now sufficiently strong for FDA to conclude that
lead acetate is unsafe pursuant to the Delaney Clause in 21 U.S.C.
379e(b)(5)(B).''
    2. ``FDA's 1980 decision rested primarily on a single industry
study'' that had ``serious flaws.''
    3. ``Exposure evidence since 1980 shows that skin absorption of
lead acetate may be more significant than FDA considered.''
    4. ``Overall exposure to lead in the United States has dropped
since 1980 so FDA's conclusion that the exposure was insignificant is
no longer valid.''
    5. ``Post-1980 evidence indicates that lead acetate is likely to be
ingested from typical use.''

    6. ``Canada and Europe found the use of lead acetate as a color
additive to be unsafe.''
    Based on these arguments, the petitioners assert that the evidence
available since lead acetate's permanent listing in 1980 demonstrates
that there is no longer a reasonable certainty that no harm would
result from the use of lead acetate in hair dyes, and, therefore, the
regulation authorizing this use as a color additive should be repealed.
The petitioners submitted in vitro and in vivo nonclinical and clinical
peer-reviewed publications, monographs, and general reports from
associations and government agencies to support their assertions.
    In section V that follows, FDA provides assessments of the
petitioners' assertions and their supporting information. FDA's review,
assessment, and evaluation of the petition are detailed in our two
review memoranda (Refs. 2 and 3). In FDA's review of the petition, we
considered relevant studies and publications on lead and lead
compounds, including lead acetate.

V. Review of the Petition

A. Petitioners' Assertion No. 1

    ``Toxicological evidence since 1980 shows there is no safe level of
exposure to lead compounds,'' and ``scientific evidence substantiating
a direct correlation between lead exposure and human carcinogenicity is
now sufficiently strong for FDA to conclude that lead acetate is unsafe
pursuant to the Delaney Clause in 21 U.S.C. 379e(b)(5)(B).'' To support
this assertion, the petition cites ``evidence with respect to lead
acetate as a carcinogen,'' including that the National Toxicology
Program (NTP) has designated lead and lead compounds to be ``reasonably
anticipated to be a human carcinogen'' based on ``limited evidence in
humans, and sufficient evidence of carcinogenicity in experimental
animals.'' The petition also cites ``evidence of health effects other
than cancer,'' specifically that lead (as elemental lead and lead
compounds, including lead acetate) ``has other adverse effects across
multiple systems at low levels,'' ``is a potent neurotoxin with no safe
level of exposure for children,'' and ``is particularly harmful to
pregnant women.'' The petition also provides toxicological monographs,
profiles, and reports on lead and lead compounds available since 1980
to support their view that lead acetate applied to the scalp is not
safe.
    The information provided in the petition to support their assertion
that there is no safe level of exposure to lead and its compounds
includes reports and publications by government agencies and
professional organizations, including an NTP monograph on Health
Effects of Low-Level Lead (2012), Centers for Disease Control and
Prevention (CDC) reports on lead (2009, 2015), Agency for Toxic
Substances and Disease Registry (ATSDR) toxicology profile for lead
(2007), an article on the Prevention of Childhood Lead Toxicity from
the American Academy of Pediatrics Council on Environmental Health
(2016), Environmental Protection Agency's Integrated Risk Information
System Chemical Assessment Summary on lead and lead compounds, and an
abstract of the risk assessment of lead acetate conducted by Health
Canada (2008). The petitioners also provide abstracts to published in
vivo and in vitro animal and human studies, and links to the 2014 NTP
report on carcinogenicity from exposure to lead and its compounds,
including lead acetate.
    FDA Assessment: FDA reviewed the peer-reviewed publications and
monographs provided in the petition and other relevant information in
our evaluation of the safety of the use of lead acetate in hair dyes
(Ref. 2) and agrees with the petitioners that there is no evidence
available at this time to determine a safe level of exposure to lead or
lead compounds intentionally used as a color additive in hair dyes.
    The toxicologic effects of lead exposure have been well-documented,
and FDA has taken several actions to protect the public from exposure
to lead in FDA regulated products, including prohibiting the use of
tin-coated lead foil capsules on wine bottles (61 FR 4816, February 8,
1996 (now codified at 21 CFR 189.301)) and prohibiting the use of lead-
soldering in food cans (60 FR 33106, June 27, 1995 (now codified at 21
CFR 189.240)) (see also 58 FR 33860 at 33864 through 33866, June 21,
1993 (discussing the health effects of adult exposure to lead); and see
generally https://www.fda.gov/Food/FoodborneIllnessContaminants/Metals/ucm2006791.htm and https://www.fda.gov/Cosmetics/ProductsIngredients/PotentialContaminants/ucm388820.htm (identifying other actions by FDA's
Center for Food Safety and Applied Nutrition concerning both childhood
and adult exposure to lead in food, food containers, and cosmetics)).
    The risks of lead exposure are particularly high in utero, infancy,
and in early childhood; CDC has stated that there is no safe blood lead
level in children, and that even low levels of lead in blood have been
shown to affect IQ, ability to pay attention, and academic achievement
(Ref. 4). As part of its program to prevent childhood lead poisoning,
CDC has recommended 5[micro]g/dL as the reference blood lead level to
identify children who have been exposed to lead and who require case
management (Ref. 4).
    Lead exposure also poses significant health risks to adults (Refs.
5 and 6). These risks include hypertension, peripheral nerve
dysfunction, and red blood cell protoporphyrin elevation (see 58 FR
33860 at 33864). A growing body of evidence indicates that adults, like
children, may experience adverse health impacts from exposure to levels
of lead lower than those previously believed to be harmful. For
example, in 2012, the NTP provided evidence of adverse effects of
exposure to low levels of lead (less than 10 [micro]g/dL) in adult
humans based on epidemiological evidence. The NTP concluded that there
is sufficient evidence for decreased glomerular filtration rate (in the
kidney) in adults and reduced fetal growth in pregnant women at blood
lead levels less than 5 [micro]g/dL; increased blood pressure,
hypertension, and essential tremor in adults at blood lead levels less
than 10 [micro]g/dL; and adverse changes in sperm parameters in men, as
well as increased time to achieve pregnancy, at blood lead levels
greater than or equal to 15-20 [micro]g/dL (Ref. 2). In 2011, the Joint
Food and Agriculture/World Health Organization (FAO/WHO) Expert
Committee on Food Additives (JECFA) withdrew the previously established
Provisional Tolerable Weekly Intake (PTWI) for lead and concluded that
it was not possible to establish a new PTWI that would be considered
health protective (Ref. 7). Additionally, the U.S. Environmental
Protection Agency has set the maximum contaminant level goal for lead
in drinking water at zero (Ref. 8). Regarding the information provided
in the petition on the carcinogenicity of lead, we discuss the
relevance of this information to FDA's decision on this petition in
section VII.

B. Petitioners' Assertion No. 2

    ``FDA's 1980 decision rested primarily on a single industry study''
by Moore et al. (Ref. 1) that had ``serious flaws.'' The petitioners
contended that results from test conditions with higher absorption
values, e.g., scratched skin, were excluded in the final analysis,
while those from test conditions that resulted in lower absorption
values e.g., ``wet'' and ``cream'' applications, were all included. The
petitioners also noted that Moore et al. excluded all the results of
the 24-hour ``whole body'' count and relied only on the 12-hour data
after deciding that the increased absorption

from the 12 to 24 hours' measurements reflected ``mechanical damage''
from washing the test substance from the skin after 12 hours. The
petitioners stated that the 24-hour ``non-scratch'' average absorption
was two times greater than the 12-hour average. Additionally, the
petitioners stated that Moore et al. may have only measured a
proportion of the lead absorbed because in calculating the ``whole-
body'' count they assumed that the transport and distribution of lead
acetate through the skin is the same path as an intravenous solution of
a known quantity of lead chloride used to establish the relationship
between radioactivity in the calf region and the whole body, which the
petitioners claim is an assumption that more recent studies call into
question. The petitioners also questioned some assumptions made by
Moore et al., claiming no references were cited to support these
assumptions (e.g., that 6 milliliters (ml) of the lead acetate
formulation is normally applied, of which 0.18 ml would reach the
scalp, and 612 [micro]g of lead would reach the scalp per hair dye
application). The petitioners noted that instructions for use included
in lead acetate hair dye packages do not typically specify amount to be
applied to hair and that the amount applied would vary depending on the
amount of hair.
    FDA Assessment: We considered the deficiencies claimed by the
petitioners with the percutaneous absorption study conducted by Moore
et al. and conducted our own re-evaluation of that study (details in
Ref. 2). We agree with the petitioners that the study conducted by
Moore et al. may not have fully accounted for all the lead that may
have been absorbed and localized in extracellular fluid compartments,
such as saliva and sweat. Although the approach of estimating whole
body uptake of lead based on measured activity in the calf region may
have partially captured lead in these extracellular fluids, newer data
suggest that looking at blood lead levels alone underestimates exposure
to lead that would have localized in other compartments (Ref. 2).
    Regarding the assertion that Moore et al. did not use the ``worst-
case scenario'' by excluding in its final analysis results from whole-
body monitoring collected from 12 to 24 hours, results from the 24-hour
``non-scratch'' whole-body monitoring data, and results from the
scratched skin scenario, and including results from test conditions
that resulted in lower absorption values (e.g., ``wet'' and ``cream''
applications), we agree that this may have resulted in limiting the
average absorption values. Regarding the assertion that some
assumptions made by Moore et al. are unsupported (e.g., that 6 ml of
the lead acetate formulation is normally applied, of which 0.18 ml
would reach the scalp, and 612 [micro]g of lead would reach the scalp
per hair dye application), we note that although these assumptions may
not reflect a worst-case use scenario, there is a study that was
submitted in support of the petition for permanently listing lead
acetate (CAP 3C0107) that evaluated the amount of lead acetate that
reached the scalp on human subjects from application of a known volume
of the hair dye that was characterized in the study as a typical
application volume. Results from that study showed that the average
amount of lead acetate that reaches the scalp from application of 7 ml
of hair dye is approximately 3 percent of the amount applied.
    As stated, we also conducted our own re-evaluation of the study by
Moore et al. and identified the following deficiencies that we believe
may have resulted in underestimation of lead exposure (Ref. 2):
    (1) The study was conducted with formulations containing 6
millimole per liter (mmol/L) or 9 mmol/L lead acetate (equivalent to
0.12 or 0.18 percent lead), respectively, which are three to five times
lower than the approved maximum use level (0.6 percent lead) in hair
dyes.
    (2) The ages of the eight male test subjects ranged from 20 to 35
years. FDA notes that most people who use lead acetate-containing hair
dye products would typically be age 50 years or older. The subjects
were therefore not considered representative of the targeted older
population. This is important because the skin in older people is
different from the skin in younger people.
    (3) The test formulation was applied to the skin on the forehead of
subjects, whereas lead acetate-containing hair dye is intended to be
applied to hair on the scalp. FDA notes that there are well documented
differences in the composition and functionality of skin tissue from
the scalp and skin tissue from other regions of the body, including the
forehead (Ref. 2). For example, scalp skin tissue is thicker and
carries more blood than other skin tissue. Thus, applying the test
substance to the forehead and non-scalp skin, like the forehead, to
assess percutaneous absorption, may not mimic absorption through the
scalp.
    (4) The test formulation(s) were reportedly applied to a skin
surface area of 8 to 10 square centimeters (cm\2\) on the forehead. FDA
notes that lead acetate-containing hair dye is intended to be applied
to the full scalp that has a skin surface area of approximately 580
cm\2\. Applying the test formulation to a surface area substantially
less than 580 cm\2\ is not representative of the intended condition of
use. Therefore, using a surface area of 8 to 10 cm\2\ likely yielded
results that underestimated the percentage of lead acetate that was
transdermally absorbed. Additionally, test results obtained from
applying the formulation to a small surface area on the forehead would
also affect the accuracy of extrapolation to account for the entire
surface area of the scalp.
    (5) The test formulations applied to the forehead were removed by
washing with soap 12 hours after application. FDA notes that the 12-
hour application period in the Moore et al. study may be too short to
assess the full extent of percutaneous absorption of lead acetate under
the intended conditions of use, which in some cases could remain on the
scalp for 24 hours or longer thereby increasing the amount of lead
percutaneously absorbed.

C. Petitioners' Assertion No. 3

    ``Exposure evidence since 1980 shows that skin absorption of lead
acetate may be more significant than FDA considered.'' To support this
assertion, the petitioners provide several peer-reviewed studies
published since 1980, which they claim demonstrate that the capacity of
the skin to absorb lead is more significant than FDA estimated in 1980.
The studies included a wide-ranging collection of occupational
exposures to in vivo (human and animal) and in vitro (using human or
animal skin) testing.
    FDA Assessment: The petitioners did not provide data on dermal
absorption of lead acetate generated under the intended use conditions
for hair dye products and did not provide an updated estimated exposure
that would result from typical chronic use of lead acetate-containing
hair dyes. However, to support their assertion that skin absorption of
lead acetate may be greater than FDA previously estimated, the
petitioners provided information that raised valid scientific questions
about the adequacy of the study that FDA relied on to support the
listing of lead acetate in Sec.  73.2396. The petition cited peer-
reviewed publications describing nonclinical (in vitro and in vivo) and
clinical studies to demonstrate dermal absorption of lead and lead
compounds, including lead acetate. FDA reviewed these publications and
other available pertinent publications and information on the dermal
absorption of lead and lead acetate (Ref. 2). Following the

review, FDA concluded that the submitted publications demonstrate that
dermally applied lead acetate and other lead-containing compounds
penetrate human and animal skin, and report absorption of dermally
applied lead and lead compounds ranging from 0.018 to 29 percent (the
latter being under conditions of occlusion). In addition, some of the
studies show that dermally absorbed lead distributes to extracellular
fluid compartments including sweat and saliva, which the petitioners
argued may contribute to an increase in lead exposure that was not
previously accounted for in the Moore et al. publication (Ref. 2).
However, we note that not all studies evaluated lead acetate, and not
all the study designs were adequate. For example, the number of test
subjects used in some studies was not adequate to ensure sufficient
statistical power of the study, while in many studies, the surface
area, location of application of the test substance, and the amount
applied did not appropriately reflect the intended conditions of use of
lead acetate to color hair on the scalp. These limitations made
interpretation of the combined results from these studies difficult,
and FDA was unable to reconcile all the reported findings related to
absorption percentages and the lead levels claimed to be present in
sweat and saliva (Ref. 2).
    Given the deficiencies identified by FDA in the study by Moore et
al. that may have resulted in underestimation of the amount of lead
acetate that is transdermally absorbed, FDA chose to conduct further
research on potential absorption from this use. FDA used in silico
modeling (ConsExpo, Netherlands (Ref. 9)) to predict the percentage of
dermal absorption of lead that may result from application of lead
acetate hair dye to hair on the full human scalp based on empirically
derived diffusion coefficients. Contrary to the 0 to 0.3 percent lead
absorption reported by Moore et al. (Ref. 1), the results from our in
silico modeling predicted higher levels of lead absorption from dermal
application of lead acetate hair dyes containing 0.6 percent lead to
the entire scalp under the intended conditions of use (Ref. 2).
    To calculate the maximum amount of lead that could be absorbed, FDA
utilized its modeled percent absorption values and the estimated levels
previously reported in CAP 3C0107 (0.18 ml of hair dye reaching the
scalp), considering an application of 6 ml of hair dye containing the
maximum permitted 0.6 percent lead to the surface area of the full
human scalp (580 cm\2\)--rather than only the 10 cm\2\ area on the
forehead--for 24 hours. Assuming that the hair dye would be applied two
times per week, FDA estimated that the daily exposure to lead would be
significantly higher than what was previously thought in 1980 (see
details in Ref. 3).

D. Petitioners' Assertion No. 4

    ``Overall exposure to lead in the United States has dropped since
1980 so FDA's conclusion that the exposure was insignificant is no
longer valid.'' The petitioners argue that, since 1980, ``both
exposures and blood lead levels have dropped dramatically as a result
of Congressional action to limit lead in consumer products and reduce
exposure to the legacy of lead uses.'' The petitioners provide
information to demonstrate that the average blood lead level of an
adult in the United States has decreased dramatically since 1980.
    FDA Assessment: In the 1980 final rule on lead acetate, FDA stated
that the average U.S. adult steady-state blood lead level was
approximately 17 [micro]g/dL. This amount was retained from the initial
35 [micro]g of lead that was absorbed and internalized per day
following normal human daily lead intakes of 100 to 500 [micro]g from
all food and environmental sources (45 FR 72112 at 72113). Based on the
National Health and Nutrition Examination Survey (NHANES) results for
2015-2016, the geometric mean and 50th percentile (median) blood lead
levels for U.S. adults 20 years and older were reported to be 0.920
[micro]g/dL (95 percent confidence interval of 0.862-0.982 [micro]g/dL)
and 0.880 [micro]g/dL (95 percent confidence interval of 0.810-0.960
[micro]g/dL), respectively (Ref. 10). Therefore, we agree with the
petitioners that the average adult blood lead level in the United
States has decreased significantly since 1980 and our conclusion in
1980 that exposure to lead from the listed use of lead acetate hair dye
is insignificant is no longer valid.

E. Petitioners' Assertion No. 5

    ``Post-1980 evidence indicates that lead acetate is likely to be
ingested from typical use.'' The petitioners provide publications by
Mielke et al. (1997) (Ref. 11) and Deeb et al. (2014) (Ref. 12) to
support their assertion that lead acetate in hair dye is likely to be
ingested from typical use of lead acetate-containing hair dye, by both
users of the dye and non-users (including children), from hand-to-mouth
activity after contacting objects such as a faucet and comb
contaminated with the hair dye or from touching a user's hair.
    FDA Assessment: The study by Mielke et al. measured the lead
content of hair dyes and lead residues on hands and on other surfaces,
including combs, hair dye containers, hair drier handles, faucets, and
telephone receivers, by users after applying lead acetate hair dye to
their hair. Mielke et al. reported a wide range of residual lead levels
on hands and surfaces touched by the hair dye user. FDA notes that the
study results show a potential for lead from the lead acetate-
containing hair dye product to transfer to other surfaces from the
hands that have been in contact with the lead acetate-containing hair
dye. However, the study by Mielke et al. did not evaluate ingestion of
lead from these contaminated surfaces. Therefore, this study does not
demonstrate that lead acetate is likely to be ingested from its use in
hair dye. Deeb et al. reported on a case of a 52-year old male patient
who presented with adverse effects attributed to repeated application
of lead acetate-containing hair dye on his beard. We note that this is
a report on one person that applied the hair dye to facial hair
contrary to the required cautionary statement on the product. The color
additive lead acetate is not approved for use in coloring facial hair
and this would be considered a misuse of the product.
    Therefore, FDA concludes that the information provided by the
petitioners is not sufficient to support their assertion that ingestion
is likely to occur from the approved use of lead acetate in hair dye
(Ref. 2). Furthermore, FDA has not identified any other relevant
scientific publications that demonstrate ingestion resulting from the
regulated use of lead acetate in cosmetics intended for coloring hair
on the scalp.

F. Petitioners' Assertion No. 6.

    ``Canada and Europe found the use of lead acetate as a color
additive to be unsafe.'' The petitioners make this assertion based on
the decision of Health Canada and the European Union (EU) Scientific
Committee on Cosmetic Products and Non-Food Products (SCCNFP) to
prohibit the use of lead acetate in cosmetic products sold in Canada
and the EU, respectively.
    FDA Assessment: FDA has made its own determination on this petition
based on our authority under the FD&C Act, independent of the actions
taken by Canada and Europe regarding the use of lead acetate in hair
dyes. However, we acknowledge that in 2004, the EU's SCCNFP evaluated
and issued an opinion on the use of lead acetate as a cosmetic
ingredient, concluding that lead acetate is classified as ``toxic to
reproduction,'' ``may cause harm to the unborn child,'' and that lead
acetate should not be intentionally added to

cosmetic products marketed in the EU. Based on this opinion, the EU
prohibited the use of lead acetate in cosmetic products in 2004 (Ref.
13).
    FDA also acknowledges that Health Canada found that lead exposure
resulting from regular use of lead acetate hair dyes when combined with
other sources of lead exposure would result in an increasing cumulative
exposure for lead that would potentially have adverse effects,
particularly in sensitive populations. In 2005, based on data
indicating skin absorption and possible links to carcinogenicity and
reproductive toxicity, Health Canada prohibited the use of lead acetate
in cosmetic products. Lead acetate-containing hair dyes have not been
sold in the Canadian market since 2008 (Ref. 2).

VI. Updated Evaluation of Safety

    During FDA's review of the petition, we evaluated the information
provided by the petitioners and other information that has become
available since 1980 when we listed lead acetate for use in hair dye to
determine if there is still a reasonable certainty of no harm from the
use of this color additive. FDA's basis for listing lead acetate in
1980, as previously stated, was that the absorbed amount of lead from
hair dye containing lead acetate was ``miniscule'' when compared to the
average person's background blood lead level and that the resulting
increase in exposure from lead acetate-containing hair dye would have
no discernible effect on the steady-state blood lead level. Our most
recent review of the published literature (Ref. 2), combined with the
flaws identified in the Moore study (see section V.B.), suggest that
exposure to lead from the use of lead acetate-containing hair dyes is
likely to be higher than was estimated in 1980. Considering all the
information currently available, the data do not support the safe use
of lead acetate as a color additive in cosmetics intended for coloring
hair on the scalp.
    In the 1980 final rule on lead acetate, FDA stated that the average
person had a steady-state blood lead level of approximately 17
[micro]g/dL (45 FR 72112 at 72113). This amount was retained from the
initial 35 [micro]g of lead that was absorbed and internalized per day
following normal human lead intakes of 100 to 500 [micro]g from all
food and environmental sources. As discussed previously, the median
blood lead level for U.S. adults 20 years and older based on 2015-2016
NHANES survey data was 0.88 [micro]g/dL (Ref. 10). The NHANES data on
blood lead levels indicates that lead exposure has decreased
significantly in the U.S. general population. As a result, any increase
in exposure to lead resulting from use of lead acetate-containing hair
dye can no longer be considered insignificant in terms of public
health.
    Considering: (1) The lack of evidence of a safe level of exposure
for lead; (2) the reported adverse effects associated with low levels
of lead exposure reported by NTP (discussed in section V.A.); (3) the
statements and current recommendations by CDC and JECFA on lead
exposure (discussed in section V.A.); (4) the deficiencies of the
percutaneous absorption study by Moore et al. that may have resulted in
an underestimate of exposure to lead from the use of lead-acetate
containing hair dye (discussed in section V.B.); and (5) the
significant reduction in median blood lead levels since 1980 (discussed
in section V.D.), FDA concludes that the original basis for listing
lead acetate is no longer valid and that there is no longer a
reasonable certainty that no harm would result from the use of lead
acetate as a color additive in cosmetics intended to color hair on the
scalp.

VII. Applicability of the Delaney Clause

    The Delaney Clause consists of two parts. The first part (section
721(b)(5)(B)(i) of the FD&C Act) pertains specifically to ingested
color additives. The second part (section 721(b)(5)(B)(ii) of the FD&C
Act) pertains to non-ingested color additives. In the 1980 final rule,
FDA explained that because the first part of the Delaney Clause
(section 721(b)(5)(B)(i) of the FD&C Act) is limited to uses that will
or may result in ingestion, it does not apply to the use of lead
acetate in hair dye used on the scalp (45 FR 72112 at 72115). In the
final rule, FDA also determined, after evaluating scientific evidence
relevant to the carcinogenic effects in experimental animals from
feeding studies, that these studies are neither ``appropriate'' nor
``relevant'' to lead acetate used in hair dye, and therefore there was
no basis to find the use of lead acetate in hair dye used on the scalp
to be unsafe pursuant to the second part of the Delaney Clause (section
721(b)(5)(B)(ii) of the FD&C Act).
    The petitioners argue that the 2004 NTP report designating lead and
lead compounds (including lead acetate) as ``reasonably anticipated to
be human carcinogens based on limited evidence of carcinogenicity from
studies in humans and sufficient evidence of carcinogenicity from
studies in experimental animals,'' other published in vitro studies,
and occupational exposure studies submitted in the petition are
sufficient to make the conclusion that lead acetate is unsafe and that
section 721(b)(5)(B) of the FD&C Act should apply (Ref. 2). The
petitioners argue that the first part of the Delaney Clause should
apply based on their assertion that lead acetate in hair dye is likely
to be ingested from typical use of lead acetate-containing hair dye for
both users of the dye and non-users (including children), from hand-to-
mouth activity after contacting objects such as a faucet contaminated
with the hair dye or a user's hair with the dye--in other words, that
there is incidental ingestion resulting from the intended use of the
lead acetate in hair dye. To support this assertion, the petitioners
submit publications by Mielke et al. and Deeb et al. (discussed in
section V.E.). FDA concluded that the petition does not provide
sufficient scientific evidence to support the petitioners' assertion of
incidental ingestion resulting from typical use of lead acetate-
containing hair dye. Because FDA has determined that the petition does
not provide sufficient scientific evidence to support the assertions of
ingestion from the use of lead acetate-containing hair dye, FDA has not
found it necessary as part of its petition response to determine
whether the first part of the Delaney Clause would apply to incidental
ingestion of lead acetate from its use in hair dye.
    The petitioner did not submit any information demonstrating
carcinogenicity via dermal exposure, and FDA is not aware of any such
information; FDA continues to find that the available animal feeding
studies are not applicable or relevant to dermally applied lead acetate
hair dyes under section 721(b)(5)(B)(ii) of the FD&C Act.

VIII. Comments on the Notice of Petition

    We provided 60 days for comments on the notice of petition. A total
of 220 individual comments were submitted to the docket after the
notice of petition published. One group submitted a comment on behalf
of 61 organizations, and another group submitted a comment supported by
26,198 signatures that they collected that were all in support of the
petition. Overall, most of the comments did not contain any substantive
new data or information that could inform FDA's evaluation of the
petition. The overwhelming majority of the individual comments
expressed support for granting the petition based on reported adverse
health effects of lead and urged FDA to repeal the regulation.
    (Comment 1) One comment, submitted by Combe, Inc. (Combe) urged FDA
to deny the petition. Combe states that, in the 1970s, it marketed a
cream-based hair dye product

containing 0.6 percent lead acetate trihydrate (0.34 percent lead) and
a liquid formula containing 0.4 percent lead acetate trihydrate (0.23
percent lead). In 1998, Combe reformulated its liquid and foam lead
acetate hair dye products to reduce the lead content. Combe states that
the reformulated liquid product contains 0.28 percent lead acetate
trihydrate (0.153 percent lead) and the foam product contains 0.25
percent lead acetate trihydrate (0.138 percent lead), thereby reducing
the amount of lead absorbed daily to a level lower than the amount FDA
considered to be safe in 1980. In its comment, Combe provides exposure
estimates based on these reformulation levels.
    Combe funded the 1978 radioactive tracer skin lead absorption study
that was required by FDA (published by Moore et al. in 1980 (Ref. 1)),
and emphasized that this study remains the only human skin lead
absorption study using a hair dye formulation. Combe maintains that the
amount of lead resulting from the use of its lead acetate hair dyes is
trivial and considers the exposure to be essentially zero. Combe
considers the studies submitted by the petitioners to be either
inadequate or not pertinent to evaluating the safety of lead acetate
under the intended conditions of use of the hair dye.
    (Response) FDA agrees with Combe that some of the studies submitted
in the petition had deficiencies in their designs, and the study
results were inconsistent and difficult to interpret. FDA also agrees
with Combe that the 1978 radioactive tracer skin lead absorption study
(published in 1980 by Moore et al. (Ref. 1)) is applicable for studying
human skin lead absorption. However, as discussed in section V, FDA
identified several significant deficiencies in the Moore et al. study.
In particular, Moore et al. applied the formulation to an 8 to 10 cm\2\
surface area on the forehead, which is not consistent with the intended
conditions of use for the hair dye product, this may have resulted in
lowering absorption and underestimating the exposure to lead.
    We acknowledge that the reformulation of Combe's hair dye products
likely reduces exposure to lead as compared to use at the maximum
permitted level. However, the regulation allows for use up to 0.6
percent lead in hair dyes; therefore, FDA must evaluate the safety of
this maximum permitted use level. FDA also notes that Combe's updated
estimated exposures for the reformulated products still relied on the
dermal absorption results from the 1978 study that applied the test
substance to a small surface area on the forehead. Based on newer
information available, application of formulations containing lead
acetate to small skin surface area significantly limits the percentage
of absorption, likely resulting in underestimating the exposure.
    (Comment 2) Combe discusses the petitioners' reliance on the
regulatory decisions by the EU and Canada to ban lead acetate. Combe
refers to these decisions as grounded in the``precautionary
principle,'' and states that the decisions were nonscientific
resolutions of controversial issues that resulted in regulatory
actions. Combe argues that such an approach is not permitted under the
risk-based science standards required by the FD&C Act.
    (Response) FDA is not relying on the decisions made by regulatory
bodies of other governments in this action. Rather, FDA's determination
is based on whether the available scientific evidence shows that there
is a reasonable certainty of no harm from the use of this color
additive.
    (Comment 3) Combe states that since the 1960 Color Additive
Amendments, FDA has issued several color additive (and food additive)
regulations and that many of these regulations include specification
limits for lead content that FDA considers to be ``safe.'' Combe urges
that, in its administrative and enforcement actions, FDA must be
consistent in implementing the FD&C Act with respect to similar
matters. Combe also asserts that the 10 parts per million (ppm) maximum
lead level that FDA recommended for lead as an impurity in cosmetic lip
products and externally applied cosmetics products in the draft
guidance document entitled ``Lead in Cosmetic Lip Products and
Externally Applied Cosmetics: Recommended Maximum Level Guidance for
Industry'' is an ``approval'' and means that the exposure from its
reformulated products should be considered safe. Specifically, Combe
asserts that the ``0.24 [micro]g per day lead exposure that FDA
determined is safe for adults from lipstick is 5 times more than the
0.046 [micro]g per day lead exposure for adults from lead acetate in
the current post-1998 Grecian Formula product.''
    (Response) FDA acknowledges that, since 1960, we have issued
several color additive and food additive regulations that include
maximum specification limits for lead (and other contaminants) that
manufacturers are unable to avoid through good manufacturing practices
and might be present as an impurity in the finished additives. However,
we note that, unlike hair dyes, in which lead acetate is intentionally
added as an ingredient to achieve a coloring effect, these
specification limits are for lead that may be present as an impurity in
an approved additive. We also note that the specification limits for
lead impurities in the finished additives are significantly lower than
the 0.6 percent lead level (equivalent to 6,000 ppm) approved in Sec.
73.2936 for use in hair dye products and the levels in Combe's
reformulated hair dye products of 0.153 percent lead (equivalent to
1,530 ppm lead) and 0.138 percent lead (equivalent to 1,380 ppm lead).
Typically, the levels specified for lead impurities in finished color
additives and food additives are 20 ppm or lower. Such impurities might
result during the manufacture of the additive (e.g., from impurities in
starting materials) or occur naturally and is not the additive itself.
FDA generally sets such specifications because it can be difficult to
completely eliminate the presence of impurities such as lead.
    The FDA draft guidance that Combe refers to recommends 10 ppm as
the maximum level for lead as an impurity (not as an ingredient) in
cosmetic lip products and externally applied cosmetics that are
marketed in the United States. The estimated exposure of 0.24 [micro]g/
d to lead from cosmetic lip products that Combe refers to was a maximum
exposure estimated by FDA based on incidental ingestion of lipstick
containing lead at 10 ppm. However, contrary to Combe's assertions, our
draft guidance is not an approval of this use, nor is it a safety
determination. FDA considers the recommended maximum lead level of 10
ppm to be an achievable impurity level, with good manufacturing
practices, for a wide range of cosmetics products. Unlike hair dyes
where lead acetate is intentionally added as an ingredient to achieve a
coloring effect, this recommended maximum level is for lead that may be
present as an impurity in certain cosmetics.
    FDA disagrees that it is being inconsistent in implementing the
FD&C Act if it repeals the regulation regarding the use of lead acetate
in hair dye under our color additive authority, while also establishing
specifications for lead as an impurity in certain additives and
providing a recommended maximum level for lead as an impurity in
certain cosmetics. These actions are consistent with FDA's authority
for color additives, food additives, and cosmetics, as well as our
public health goal of reducing consumer exposure to lead to the
greatest extent that is technically feasible.

IX. Conclusion

    Following a full evaluation of the data submitted in support of CAP
7C0309 and other pertinent data and information, FDA has concluded that
the data currently available no longer demonstrate that there is a
reasonable certainty of no harm from the use of lead acetate as a color
additive in hair dyes authorized under Sec.  73.2396. This conclusion
is based on the recognition of the current consensus that there is no
safe exposure level for lead, deficiencies identified from our re-
evaluation of the 1980 skin absorption study by Moore et al. that may
have resulted in an underestimate of exposure to lead from its use in
hair dye, and the fact that blood lead levels in the United States have
dropped significantly since 1980, so we no longer can conclude that
exposure to lead from lead acetate-containing hair dye has no
discernible effect on the steady-state blood lead level. Therefore, to
protect the public health, we are amending 21 CFR part 73 as set forth
in this document. Upon the effective date (see DATES), use of lead
acetate as a color additive in cosmetics intended for coloring hair on
the scalp is no longer authorized.
    FDA is exercising enforcement discretion for a period of 12 months
from the effective date of the final rule regarding marketed hair dye
products that contain the color additive lead acetate to provide an
opportunity for industry to deplete the current stock of hair dye
products with lead acetate and reformulate products prior to enforcing
the requirements of this final rule. Such products must comply with the
requirements of Sec.  73.2396, including the specifications, uses and
restrictions, and labeling requirements. This period of enforcement
discretion takes into consideration the fact that bismuth citrate,
which is listed in 21 CFR 73.2110 for use in cosmetic hair dye products
at a level up to 2.0 percent weight/volume, is already being used as an
alternative for lead acetate in hair dye products marketed both in the
United States and other countries.

X. Public Disclosure

    In accordance with Sec.  71.15 (21 CFR 71.15), the petition and the
documents that we considered and relied upon in reaching our decision
to approve the petition will be made available for public disclosure
(see FOR FURTHER INFORMATION CONTACT). As provided in Sec.  71.15, we
will delete from the documents any materials that are not available for
public disclosure.

XI. Analysis of Environmental Impact

    We previously considered the environmental effects of this rule, as
stated in the April 4, 2017, Federal Register notice of petition for
CAP 7C0309. We stated that we had determined, under 21 CFR 25.32(m),
that this action is of a type that does not individually or
cumulatively have a significant effect on the human environment such
that neither an environmental assessment nor an environmental impact
statement is required. We have not received any new information that
would affect our previous determination.

XII. 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.

XIII. Objections

    This rule is effective as shown in the ``DATES'' section, except as
to any provisions that may be stayed by the filing of proper
objections. If you will be adversely affected by one or more provisions
of this regulation, you may file with the Dockets Management Staff (see
ADDRESSES) either electronic or written objections. You must separately
number each objection, and within each numbered objection you must
specify with particularity the provision(s) to which you object, and
the grounds for your objection. Within each numbered objection, you
must specifically state whether you are requesting a hearing on the
particular provision that you specify in that numbered objection. If
you do not request a hearing for any particular objection, you waive
the right to a hearing on that objection. If you request a hearing,
your objection must include a detailed description and analysis of the
specific factual information you intend to present in support of the
objection in the event that a hearing is held. If you do not include
such a description and analysis for any particular objection, you waive
the right to a hearing on the objection.
    Any objections received in response to the regulation may be seen
in the Dockets Management Staff office between 9 a.m. and 4 p.m.,
Monday through Friday, and will be posted to the docket at https://www.regulations.gov. We will publish notice of the objections that we
have received or lack thereof in the Federal Register.

XIV. References

    The following references marked with an asterisk (*) are on display
at the Dockets Management Staff (see ADDRESSES) and are available for
viewing by interested persons between 9 a.m. and 4 p.m., Monday through
Friday; they also are available electronically at https://www.regulations.gov. References without asterisks are not on public
display at https://www.regulations.gov because they have copyright
restriction. Some may be available at the website address, if listed.
References without asterisks are available for viewing only at the
Dockets Management Staff. FDA has verified the website addresses, as of
the date this document publishes in the Federal Register, but websites
are subject to change over time.

1. Moore, M.R., P.A. Meredith, W.S. Watson, et al., ``The
Percutaneous Absorption of Lead-203 in Humans From Cosmetic
Preparations Containing Lead Acetate, as Assessed by Whole-Body
Counting and Other Techniques,'' Food and Cosmetics Toxicology,
18:399-405, 1980.
*2. Memorandum from M. K. Wyatt, Cosmetics Division, OCAC, CFSAN,
FDA to M. Harry, Division of Petition Review, OFAS, CFSAN, FDA,
September 18, 2018.
*3. Memorandum from H. Lee, Division of Petition Review, OFAS,
CFSAN, FDA to M. Harry, Division of Petition Review, OFAS, CFSAN,
FDA, September 19, 2018.
*4. Center for Disease Control and Prevention, ``What Do Parents
Need to Know to Protect Their Children?'' https://www.cdc.gov/nceh/lead/acclpp/blood_lead_levels.htm.
*5. Agency for Toxic Substances and Disease Registry (ATSDR),
``Toxicological Profile for Lead,'' August 2007. https://www.atsdr.cdc.gov/toxprofiles/TP.asp?id=96&tid=22.
*6. U.S. Department of Health and Human Services, National
Toxicology Program, ``NTP Monograph on Health Effects of Low-Level
Lead.'' https://ntp.niehs.nih.gov/ntp/ohat/lead/final/monographhealtheffectslowlevellead_newissn_508.pdf.
7. ``Evaluation of Certain Food Additives and Contaminants: Seventy-
Third Report of the Joint FAO/WHO Expert Committee on Food
Additives,'' WHO Tech Report Series No. 960. 2011. http://apps.who.int/iris/bitstream/10665/44515/1/WHO_TRS_960_eng.pdf.
*8. U.S. Environmental Protection Agency, ``Basic Information about
Lead in Drinking Water. Health Effects of Exposures to Lead in
Drinking Water. Is there a Safe Level of Lead in Drinking Water?''
https://www.epa.gov/ground-water-and-drinking-water/basic-information-about-lead-drinking-water.
9. Delmaar, J.E., M.V. Park, and J.G. van Engelen, ``ConsExpo-
Consumer Exposure and Uptake Models,'' RIVM report no. 320104004,
http://www.rivm.nl/en/Topics/C/ConsExpo.
*10. U.S. Department of Health and Human Services, Centers for
Disease Control and

Prevention, ``Fourth National Report on Human Exposure to
Environmental Chemicals, Updated Tables, March 2018, Volume One.''
https://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Volume1_Mar2018.pdf.
11. Mielke, H.W., M.D. Taylor, C.R. Gonzales, et al., ``Lead-Based
Hair Coloring Products: Too Hazardous for Household Use,'' Journal
of the American Pharmaceutical Association, NS37:85-89, 1997b.
12. Deeb, W., D. Cachia, C. Quinn, et al., ``Peripheral Neuropathy
After Hair Dye Exposure: A Case Report,'' Journal of Clinical
Neuromuscular Disease, 15:161-163, 2014.
*13. The Scientific Committee on Cosmetic Products and Non-Food
Products Intended for Consumers. Opinion Concerning Lead Acetate,
SCCNFP/0832/04, July 1, 2004. http://ec.europa.eu/health/ph_risk/committees/sccp/documents/out286_en.pdf.

List of Subjects in 21 CFR Part 73

    Color additives, Cosmetics, Drugs, Medical devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
73 is amended as follows:

PART 73--LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION

0
1. The authority citation for part 73 continues to read as follows:

    Authority:  21 U.S.C. 321, 341, 342, 343, 348, 351, 352, 355,
361, 362, 371, 379e.

Sec.  73.2396  [Removed]

0
2. Remove Sec.  73.2396.

    Dated: October 25, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-23725 Filed 10-30-18; 8:45 am]
 BILLING CODE 4164-01-P


[Federal Register Volume 82, Number 239 (Thursday, December 14, 2017)]
[Rules and Regulations]
[Page 58731]
[FR Doc No: 2017-26982]

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SECURITIES AND EXCHANGE COMMISSION

17 CFR Parts 229, 232, 239 and 249

[Release Nos. 33-10446; 34-82280; File No. S7-19-16]
RIN 3235-AL95

Compliance Date for Form 10-D Hyperlink Requirements

AGENCY: Securities and Exchange Commission.

ACTION: Notification of compliance date.

-----------------------------------------------------------------------

SUMMARY: The Securities and Exchange Commission (``Commission'') is
publishing this document to inform the public that it has set a
compliance date for its previously-adopted exhibit hyperlinking
requirements for Form 10-Ds that require hyperlinks to any exhibits
filed with Form ABS-EE. The Commission on March 1, 2017 required
registrants that file registration statements and reports subject to
the exhibit requirements under Item 601 of Regulation S-K, or that file
Forms F-10 or 20-F, to include a hyperlink to each exhibit listed in
the exhibit index of these filings, but deferred setting a compliance
date with respect to any Form 10-D that will require hyperlinks to any
exhibits filed with Form ABS-EE until the Commission announced that
technical programming changes to allow issuers to include Form 10-D and
Form ABS-EE in a single submission had been completed, and published a
notification of the compliance date for Form 10-D in the Federal
Register.

DATES: The compliance date with respect to any Form 10-D that will
require hyperlinks to any exhibits filed with Form ABS-EE is June 1,
2018.

FOR FURTHER INFORMATION CONTACT: Kayla Roberts, Special Counsel, at
(202) 551-3850, in the Office of Structured Finance, Division of
Corporation Finance, U.S. Securities and Exchange Commission, 100 F
Street NE, Washington, DC 20549.

SUPPLEMENTARY INFORMATION: On March 1, 2017, the Commission adopted
rule and form amendments requiring registrants that file registration
statements and reports subject to the exhibit requirements under Item
601 of Regulation S-K,\1\ or that file Forms F-10 \2\ or 20-F,\3\ to
include a hyperlink to each exhibit listed in the exhibit index of
these filings.\4\ To enable the inclusion of hyperlinks, the amendments
also require that registrants submit all filings on EDGAR in HyperText
Markup Language (``HTML'') format because the American Standard Code
for Information Interchange (``ASCII'') format cannot support
functional hyperlinks.\5\
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    \1\ 17 CFR 229.601.
    \2\ 17 CFR 239.40.
    \3\ 17 CFR 249.220f
    \4\ Exhibit Hyperlinks and HTML Format, Release Nos. 33-10322,
34-80132 (March 1, 2017) [82 FR 14130 (March 17, 2017)]
(``Hyperlinks Release'').
    \5\ See id. at Section I.
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    The amendments took effect on September 1, 2017 for most
registrants. Registrants that are ``smaller reporting companies,'' as
defined in Rule 405 \6\ under the Securities Act of 1933 and Rule 12b-2
\7\ under the Securities Exchange Act of 1934, or are neither ``large
accelerated filers'' nor ``accelerated filers,'' as defined in Exchange
Act Rule 12b-2, and that submit filings in ASCII will not need to
comply with the new rules until September 1, 2018, one year after the
effective date for other filers.\8\ The Commission deferred
establishing a compliance date for any Form 10-D filing that will
require a hyperlink to an exhibit filed with Form ABS-EE until
Commission staff completed programming changes to EDGAR to allow Form
10-D filers to include the Form 10-D and Form ABS-EE in a single EDGAR
submission so that the required hyperlinks could be created at the time
the Form 10-D is filed.\9\ Such programming changes have now been
completed.\10\
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    \6\ 17 CFR 230.405.
    \7\ 17 CFR 240.12b-2.
    \8\ See Hyperlinks Release, supra note 1, at Section II.B.3.
    \9\ See Hyperlinks Release, supra note 1, at n. 55 (explaining
that asset-backed issuers are required to incorporate by reference
Form ABS-EE information in Form 10-D and how the hyperlinking
requirement applies with respect to Form 10-D filings) & n.72 and
accompanying text.
    \10\ Adoption of Updated EDGAR Manual, Release No. 33-10444,
(December 8, 2017), available at https://www.sec.gov/rules/final.shtml.
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    Any registrant filing a Form 10-D on or after June 1, 2018, must
include a hyperlink to any exhibit filed with Form ABS-EE that is
included in the exhibit index of Form 10-D.\11\
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    \11\ Issuers are not required to submit their Form 10-D and Form
ABS-EE in a single submission. An issuer may file a Form 10-D and
Form ABS-EE in separate submissions and comply with the new
requirements by including an external hyperlink in the Form 10-D to
a previously filed Form ABS-EE.

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    By the Commission.

    Dated: December 11, 2017.
Brent J. Fields,
Secretary.
[FR Doc. 2017-26982 Filed 12-13-17; 8:45 am]
 BILLING CODE 8011-01-P