**Guidance for Industry**

**Labeling for Topically Applied Cosmetic Products Containing Alpha
Hydroxy Acids as Ingredients**

***DRAFT GUIDANCE***

**This guidance document is being distributed for comment purposes
only.**

Draft released for comment on December 2, 2002.

Comments and suggestions regarding this draft guidance should be
submitted by January 31, 2003 to Dockets Management Branch (HFA-305),
Food and Drug Administration, 5630 Fishers Lane, room 1061, Rockville,
MD 20852. All comments should be identified with the Docket Number
00P-1378. For questions regarding this draft guidance contact Julie N.
Barrows, (202) 418-3412.

**U. S. Department of Health and Human Services**

**Food and Drug Administration**

**Center for Food Safety and Applied Nutrition (CFSAN)**

**November, 2002**

**U.S. Food and Drug Administration**

**Center for Food Safety and Applied Nutrition**

**Office of Cosmetics and Colors**

**November 2002**

**Guidance for Industry**

**Labeling for Topically Applied Cosmetic Products Containing**

**Alpha Hydroxy Acids as Ingredients**

**Draft Guidance**

**This draft guidance represents the Agency's current thinking on
labeling for topically applied cosmetic products containing alpha
hydroxy acids as ingredients. It does not create or confer any rights
for or on any person and does not operate to bind FDA or the public. An
alternative approach may be used if such approach satisfies the
requirements of applicable statutes and regulations.**

**Sunburn Alert**

FDA has considered evidence that suggests that topically applied
cosmetic products containing alpha hydroxy acids (AHAs) may increase the
sensitivity of skin to the sun while the products are used and for up to
a week after use is stopped, and that this increased skin sensitivity to
the sun may increase the possibility of sunburn. The purpose of this
guidance is to educate manufacturers to help ensure that their labeling
for AHA-containing cosmetic products is not false or misleading. As an
interim measure, while FDA continues to review the data on AHAs to
address the potential for this increased skin sensitivity to the sun,
FDA is suggesting that the labeling of a cosmetic product that contains
an AHA as an ingredient and that is intended for topical application to
the skin or mucous membrane bear a statement that conveys the following
information.

> Sunburn Alert: This product contains an alpha hydroxy acid (AHA) that
> may increase your skin's sensitivity to the sun and particularly the
> possibility of sunburn. Use a sunscreen and limit sun exposure while
> using this product and for a week afterwards.

Alpha hydroxy acids are organic acids with a hydroxyl group on the
carbon adjacent to the carboxylic acid group. The predominant AHAs
present in cosmetic products are glycolic acid and lactic acid. Other
AHAs used in cosmetic products include citric acid, α-hydroxyoctanoic
acid, and α-hydroxydecanoic acid (Reference 1).

Starting in 1994, the Cosmetic, Toiletry, and Fragrance Association's
Cosmetic Ingredient Review (CIR) Expert Panel, FDA's AHA Review
Committee, and FDA reviewed the safety of topically applied AHAs in
cosmetic products (References 2 through 4). The reviewers evaluated
human clinical studies that investigated the effects of ultraviolet (UV)
radiation on the skin after exposure to AHAs. The studies demonstrated
that topically applied AHAs increase skin sensitivity to UV radiation
during application and that this increased skin sensitivity to UV
radiation diminishes after discontinuing application for a week.

Sensitivity to UV radiation is the main reason for the skin's
sensitivity to the sun (Reference 5). Short-term exposure to the sun may
cause sunburn and chronic long-term exposure to the sun may increase
risk of premature skin aging (Reference 5). Experimental and
epidemiological studies have demonstrated that prolonged exposure to the
UV radiation in sunlight is a primary risk factor for certain types of
skin cancer (References 6 through 8).

The human clinical studies reviewed by the CIR Expert Panel, FDA's AHA
Review Committee, and FDA provided data for the effects of UV radiation
on the skin after short-term (up to 12 weeks) topical exposure to AHAs.
The evidence from the clinical studies suggests that increased skin
sensitivity to UV radiation may increase the possibility of sunburn for
consumers. Adverse experience reports by consumers of increased sunburn
after AHA use support this conclusion (Reference 2). The increased skin
sensitivity to UV radiation also may result in other harmful effects to
the skin, but the data currently available to CFSAN are inconclusive on
this point. CFSAN is publishing this guidance and the suggested labeling
information as an interim measure to educate manufacturers to help
ensure that their labeling is not false and misleading while FDA
continues to review the data on AHA-containing products.

**AHAs in Cosmetic Products**

Since the early 1990\'s, there has been a proliferation of
AHA-containing cosmetic products available commercially and in salons
(Reference 2). AHAs have been formulated into skin products, make-up,
hair products, nail products, bath products, colognes, and suntan
preparations. Most AHA-containing products are "leave on" products that
are intended for daily use on the skin or mucous membrane or are
"discontinuous use" products that are intended to be applied to the skin
for a short period of time (e.g., less than an hour) followed by
thorough rinsing. Salon products are usually discontinuous use products.

In 1992, in its Voluntary Cosmetics Registration Program, FDA received
the first four registrations of new lines of cosmetic products
containing glycolic acid (Reference 2). (The information is an
incomplete market history as the data are reported voluntarily.) By
1997, the registrations of cosmetic product lines containing glycolic
acid increased to forty-two, as glycolic acid and lactic acid were added
to previously marketed lines of products.

From 1992 to 1996 and from 1999 to 2000, FDA conducted two market
surveys of AHA-containing skin care products and found that the
predominant AHAs present in the products were glycolic acid and lactic
acid (References 1 and 2). Other AHAs found were citric acid,
α-hydroxyoctanoic acid, and α-hydroxydecanoic acid (Reference 1).

Between 1989 and 1991, FDA received five reports from consumers that
described adverse dermatologic experiences from a line of cosmetic skin
care products that were labeled as containing AHAs, including glycolic
acid (Reference 2). The reported adverse experiences were similar and
included pigmentary changes, burning, and swelling. FDA issued a warning
letter to the manufacturer on May 13, 1992, and the products were
withdrawn from the market. Although FDA analyses found that the products
did not contain an AHA, but rather phenol and resorcinol, FDA became
aware of the expanded use of AHAs as ingredients in cosmetic products.
Between 1992 and 1993, FDA received 10 reports of adverse dermatologic
experiences with products that were determined by FDA to contain AHAs.
In 1994, the number of reports increased to 32. FDA received a total of
107 adverse dermatologic experience reports for AHA-containing skin care
products between 1992 and 2000, with the maximum number in 1994. The
reported adverse experiences include burning (43), dermatitis or rash
(33), swelling (26), pigmentary changes (15), blisters or welts (13),
skin peeling (12), itching (12), irritation or tenderness (6), chemical
burns (6), and increased sunburn (3).

**Citizen Petition from the Cosmetic, Toiletry, and Fragrance
Association**

The Cosmetic, Toiletry, and Fragrance Association (CTFA) submitted a
citizen petition, dated June 29, 2000, assigned FDA Docket No.
00P-1378/CP1, which advocated sun protection labeling for AHA-containing
cosmetic products. The petition noted that products containing AHAs
currently represent a significant portion of the \$6 billion domestic
United States skin care market; approximately 1500 stock-keeping units
of skin care products contain AHAs.

In the petition, CTFA requested that FDA issue a regulation under 21
U.S.C. 362(a) establishing labeling requirements related to sun
protection with use of cosmetic products containing AHAs. The petition
proposed the following regulation for part 701 of the Code of Federal
Regulations (21 CFR Part 701Cosmetic Labeling):

> The label and labeling of a cosmetic product that contains an alpha
> hydroxy acid ingredient that is intended to function as an exfoliant
> shall bear the following prominent and conspicuous statement:
>
> "Sun Alert: Because this product may make your skin more sensitive to
> the sun, be certain you have adequate sunscreen protection while using
> this product and for a week after you discontinue use."

**Safety Reviews of AHAs**

CTFA's CIR Expert Panel, FDA's AHA Review Committee, and FDA reviewed
the safety of topically applied AHAs in cosmetic products (References 2
through 4). The reviewers evaluated human clinical studies that
investigated the effects of ultraviolet (UV) radiation on the skin after
exposure to glycolic acid and lactic acid, as well as salts and esters
prepared from glycolic or lactic acids. The salts and esters included
ammonium, calcium, potassium, and sodium glycolates; methyl, ethyl,
propyl, and butyl glycolates; ammonium, calcium, potassium, sodium, and
triethanolamine (TEA) lactates; methyl, ethyl, isopropyl, and butyl
lactates; and lauryl, myristyl, and cetyl lactates.

The human clinical studies measured sunburn cell (SBC) formation and
change in the minimal erythema dose (MED). SBCs are apoptotic skin cells
that are produced in response to UV radiation, primarily UVB, and the
MED is the minimal amount of UV radiation needed to cause the skin to
redden (References 2 and 5). Both skin responses, SBC formation and
erythema (skin reddening), are characteristic of sunburn (Reference 5).
The studies also measured UV-induced cyclopyrimidine dimer (CPD)
formation, which is a type of DNA damage.

CTFA's CIR Expert Panel concluded from human clinical studies that AHA
ingredients in cosmetic products increase skin sensitivity to UV
radiation (UVB or solar-simulating radiation), as measured by SBC
formation, which was found on average to increase, and as measured by
change in the MED, which was found on average to decrease (Reference 3).
In its final report, published in 1998 (Reference 3), the CIR Expert
Panel reported the following conclusion: "Based on the available
information included in this report, the CIR Expert Panel concludes that
Glycolic and Lactic Acid, their common salts and their simple esters,
are safe for use in cosmetic products at concentrations ≤10%, at final
formulation pH ≥3.5, when formulated to avoid increasing sun sensitivity
or when directions for use include the daily use of sun protection.
These ingredients are safe for use in salon products at concentrations
≤30%, at final formulation pH ≥3.0, in products designed for brief,
discontinuous use followed by thorough rinsing from the skin, when
applied by trained professionals, and when application is accompanied by
directions for the daily use of sun protection."

FDA's AHA Review Committee, which met on February 12, 1997, and May 6,
1997, agreed that the evidence suggests that topical application of AHAs
increases skin sensitivity to UV radiation, as measured by increased SBC
formation and decreased MED (Reference 4). The Committee noted that in
the human clinical studies they reviewed, a small proportion of people
showed an amplified effect on increased SBC formation or decreased MED.

FDA has evaluated the CTFA citizen petition and the safety reviews of
topical application of AHAs by the CIR Expert Panel and the AHA Review
Committee. FDA also has reviewed in detail six human clinical studies
that provide data for assessing increased skin sensitivity to UV
radiation produced by use of topically applied cosmetic products
containing AHAs (Reference 2). Five of the studies measured increased
SBC formation and/or decreased MED. The sixth study measured increased
CPD formation. The studies used solar-simulating radiation and/or UVB
radiation for determining baseline MEDs and for determining changes in
MED and SBC or CPD formation. Although the studies investigated the
effects of glycolic acid, FDA believes that the effects of other types
of AHAs used in cosmetic products may be the same.

The human clinical studies that measured increased SBC formation or
decreased MED found that topical application of glycolic acid at
concentrations as low as 4% and for as short a duration as 4 days can
alter the skin's response to UV radiation. Furthermore, the skin's
enhanced sensitivity to UV radiation continues during exposure to
glycolic acid of up to 12 weeks. Thus, the studies suggest that there is
no compensatory mechanism by which the skin moderates the effects of an
AHA on sensitivity to UV radiation. The studies also found that
increased skin sensitivity to UV radiation no longer is evident 1 week
after discontinuing topical application of glycolic acid. This suggests
that AHA-induced sensitivity to UV radiation is reversible. However,
further studies are required to determine how the length of time of AHA
use affects the time required for reversal of AHA-induced effects. Skin
sensitivity to UV radiation, measured as UV-induced CPD formation, may
increase after 4 weeks of topical application of glycolic acid. However,
the increase found (8%) is not statistically significant and suggests
that further studies are required to determine the effects of AHA
exposure on UV-induced CPD formation. Finally, the addition of
sunscreens to cosmetic products containing AHAs, under some conditions
of use, may help counter increased skin sensitivity to UV radiation.

In most of the studies reviewed, a subset of subjects appeared to be
more susceptible to the effects of glycolic acid on UV-induced increased
SBC formation and decreased MED. This suggests that some individuals are
more responsive than others to AHA-induced increased skin sensitivity to
UV radiation. However, the studies did not identify any basis for
identifying this subset of sensitive individuals as a wide range of skin
types was implicated.

The human clinical studies provided data for the effects of UV radiation
on the skin after short-term (up to 12 weeks) topical exposure to AHAs.
The evidence from the clinical studies suggests that increased skin
sensitivity to UV radiation may increase the possibility of sunburn for
consumers. Adverse experience reports by consumers of increased sunburn
after AHA use support this conclusion (Reference 2). The increased skin
sensitivity to UV radiation also may result in other harmful effects to
the skin, but the data currently available to CFSAN are inconclusive on
this point.

FDA's National Center for Toxicological Research (NCTR) is currently
investigating the effects of long-term exposure to AHAs, in a
photocarcinogenicity study by the National Toxicology Program's Center
for Phototoxicology (Reference 2). The purpose of the NCTR study is to
allow quantitative determination of the effect AHA treatment (glycolic
acid) has on the induction of mouse skin cancer (SKH-1 hairless mouse)
by simulated solar radiation.

**"Sunburn Alert" AHA Labeling Statement**

In its citizen petition, CTFA requested that the labeling statement
informing consumers about measures to take when using AHA-containing
cosmetic products should say "Sun Alert: Because this product may make
your skin more sensitive to the sun, be certain you have adequate
sunscreen protection while using this product and for a week after you
discontinue use."

FDA has reviewed information on the elements of effective labeling
statements (Reference 2). This information indicates that an effective
labeling statement would begin with a signal phrase, identify the
subject of the statement, identify the consequences of not heeding the
statement, and provide instructions on what to do (or not do) to avoid
these consequences. The information suggests that removal of any of
these elements significantly decreases the perceived effectiveness of
the statement.

Based on this information, FDA has developed an alternate suggested
statement and encourages manufacturers to use the following labeling
statement for AHA-containing cosmetic products: "Sunburn Alert: This
product contains an alpha hydroxy acid (AHA) that may increase your
skin's sensitivity to the sun and particularly the possibility of
sunburn. Use a sunscreen and limit sun exposure while using this product
and for a week afterwards." FDA's basis for its suggested labeling is as
follows.

First, FDA suggests a change in the signal phrase in the AHA labeling
statement from "Sun Alert" to "Sunburn Alert". Clinical studies indicate
that increased skin sensitivity to the sun from topical application of
AHA-containing cosmetic products increases the possibility of sunburn
for consumers.

Section 352.52 (e)(2) of the CFR (21 CFR 352.52(e)(2)) provides for the
following optional "Sun alert" in the labeling of over-the-counter (OTC)
sunscreen drug products: "Sun alert: Limiting sun exposure, wearing
protective clothing, and using sunscreens may reduce the risks of skin
aging, skin cancer, and other harmful effects of the sun." The "Sun
alert" statement for OTC sunscreen drug products is intended to inform
consumers of measures to take in addition to use of sunscreens for
countering the risks of sun exposure. The suggested statement for
AHA-containing cosmetic products is intended to inform consumers of a
very different issuethe increased possibility of sunburn from using
AHA-containing cosmetic products, and the need to use sun protection
when using the products and for a week afterwards. Thus, the intended
messages to consumers for OTC sunscreen drug products and AHA-containing
cosmetic products are very different. Therefore, FDA is suggesting a
different signal phrase to help identify the different intent of the
statement for AHA-containing cosmetic products.

Second, FDA believes that the suggested AHA labeling statement should
identify to consumers the subject of the statement (the AHA ingredient
contained in the cosmetic products). Therefore, FDA is including the
phrase "This product contains an alpha hydroxy acid (AHA)" in its
recommended statement.

Third, FDA believes that the suggested AHA labeling statement should
tell consumers about the consequences of not heeding the statement (that
use of AHA-containing cosmetic products may increase their skin's
sensitivity to the sun, and that this increased skin sensitivity to the
sun may increase the possibility of sunburn). Therefore, FDA is
including the phrase "may increase your skin's sensitivity to the sun
and particularly the possibility of sunburn" in its recommended
statement.

Fourth, FDA believes that the AHA labeling statement should provide
instructions on what consumers can do to avoid these consequences (how
to minimize the possibility of sunburn). In the sunscreen monograph
published in the Federal Register of May 21, 1999 (64 FR 27666), which
established the optional "Sun alert" for OTC sunscreen drug products,
FDA stated that the purpose of that statement is to describe the role of
sunscreens in a total program to reduce harmful effects from the sun.
The statement recommends limiting sun exposure and wearing protective
clothing in addition to using sunscreens.

The CTFA petition requested that the AHA labeling statement recommend
the use of "adequate sunscreen protection" and cited the conclusion of
the CIR Expert Panel review of AHAs (Reference 3) as support for its
recommended label statement. The Expert Panel's conclusion, however,
recommends "daily use of sun protection," and does not specifically
mention sunscreens. FDA concurs with the conclusion of the Expert Panel
and therefore is recommending the language "use a sunscreen and limit
sun exposure" to suggest actions to implement the Expert Panel's
recommendation of "daily use of sun protection." The agency believes
that it is important to emphasize both steps together as part of an
overall program for reducing the possibility of sunburn when using
AHA-containing products. Sunscreens are effective for minimizing the
possibility of sunburn, but sunscreens come off. An important limitation
for sunscreens is the need for their frequent application for continued
effective sun protection. Therefore, in addition to using sunscreens,
consumers also should be mindful of limiting sun exposure.

FDA notes that wearing protective clothing is only relevant to use of
certain AHA-containing products (e.g., body lotions) and that this
recommendation is not applicable to a major use of AHA-containing
products (face creams and moisturizers). FDA is concerned that consumer
confusion over a labeling statement on a face product that recommends
consumers to "wear protective clothing" for minimizing the possibility
of sunburn from AHA use might cause consumers to discount the important
recommendations to "use a sunscreen and limit sun exposure." Therefore,
the agency has not included the phrase "wear protective clothing" in its
recommended labeling statement.

Finally, FDA has altered the phrase "for a week after you discontinue
use" to the more user friendly "for a week afterwards" in accordance
with the use of plain language in its publications.

**Function of AHA Labeling Statement**

In its citizen petition, CTFA requested that FDA establish labeling
requirements that inform consumers about measures to take when using
AHA-containing cosmetic products. FDA has reviewed the petition and
other information about labeling statements on AHA-containing cosmetic
products and other consumer products. FDA also has considered
information on consumer awareness of increased skin sensitivity from use
of AHA-containing cosmetic products.

Labeling statements on consumer products are often used for
communicating product safety information (Reference 2). The function of
a labeling statement depends on the information environment in which a
statement will be perceived and the content of the statement.

If consumers are unaware of an identified risk associated with a
product, the function of a labeling statement will be to convey new
information to the consumers. An example is the safety information
labeling statement required by FDA on iron-containing dietary
supplements and drugs (Federal Register of January 15, 1997, 62 FR
2218), which states, "WARNING. Accidental overdose of iron-containing
products is a leading cause of fatal poisoning in children under 6. Keep
this product out of reach of children. In case of accidental overdose,
call a doctor or poison control center immediately."

If consumers are aware of the identified risk, the labeling statement
will function as a reminder of the recommended precaution. One example
is the labeling statement required by the U.S. Department of Agriculture
on retail raw meat and poultry products (Federal Register of March 28,
1994, 59 FR 14528), which states, "Safe Handling Instructions. This
product was prepared from inspected and passed meat and/or poultry. Some
food products may contain bacteria that could cause illness if the
product is mishandled or cooked improperly. For your protection, follow
these safe handling instructions. Keep refrigerated or frozen; thaw in
refrigerator or microwave. Keep raw meat and poultry separate from other
foods; wash working surfaces (including cutting boards), utensils, and
hands after touching raw meat or poultry. Cook thoroughly. Keep hot
foods hot; refrigerate leftovers immediately or discard." Another
example is the labeling statement required by FDA on cartons of shell
eggs (Federal Register of December 5, 2000, 65 FR 76092), which states,
"Safe Handling Instructions: To prevent illness from bacteria: keep eggs
refrigerated, cook eggs until yolks are firm, and cook foods containing
eggs thoroughly."

FDA believes that, like the iron statement, the recommended AHA labeling
statement would help convey new information to most consumers. Both
kinds of labeled products (cosmetics and dietary supplements) are widely
used, and FDA's focus group research suggests that many consumers are
not aware of possible risks associated with use of either of these types
of products (Reference 2).

FDA also believes that, like the meat and egg statements, the AHA
labeling statement would function as a reminder of FDA's recommended
precautions to consumers who are already aware of this information.

Consumers use cosmetic products to maintain or improve the appearance of
the body. Focus group research suggests that consumers generally believe
cosmetic products are safe for their intended uses (Reference 2). FDA
does not know the extent of consumer awareness of increased skin
sensitivity to the sun from the use of AHA-containing cosmetic products.
FDA has published information about this issue in its magazine, *FDA
Consumer*, in which FDA recommends precautions that consumers should
take when using an AHA-containing product, including using an effective
sunscreen (Reference 2). The information also is available on FDA's
website at [http://www.cfsan.fda.gov/]{.underline}. However, in July
2001, as an example, only about 0.003% of U.S. households visited this
website for information on AHAs (Reference 2).

FDA has not observed that the effect of AHAs on increased skin
sensitivity to the sun has been widely publicized in the media or
popular press, unlike the effect of AHAs on skin irritation (Reference
2). (In the early 1990s, consumers frequently experienced skin
irritation from using AHA-containing cosmetic products. This concern was
widely publicized to consumers and was addressed by manufacturers
reformulating their products (Reference 3).)

To help assure consumer awareness of the potential for increased skin
sensitivity to the sun from topical use of AHA-containing cosmetic
products, FDA suggests that such products should bear information on
their labeling such as the "Sunburn Alert" that helps convey information
about the need for sun protection to avoid sunburn. FDA expects that a
label statement such as the recommended "Sunburn Alert" will be a source
of new information about sun protection for most consumers, as well as a
reminder of FDA's recommended precautions for consumers who are already
aware of the need to use sun protection when using these products
(Reference 2).

**Use Conditions for "Sunburn Alert" Labeling Statement**

To provide guidance to manufacturers on when FDA recommends that
products should bear "Sunburn Alert" labeling, the agency has
tentatively identified these use conditions:

1\. The product contains an AHA as an ingredient;

2\. The product is intended for topical application to the skin or
mucous membrane. The product may be a "leave on" product that is
intended to remain on the skin or mucous membrane or it may be a
"discontinuous use" product that is intended to be left on the skin for
a short period of time (less than an hour) followed by thorough rinsing.

**Requested Restriction of CTFA's Alert Statement to Exfoliant Use**

In its citizen petition, CTFA proposed that the regulation establishing
labeling requirements for cosmetic products that contain an AHA as an
ingredient be restricted to products that are intended to function as an
exfoliant.

FDA has traditionally determined intended use for a product from
statements in the product's labeling. Between 1992 and 2000, FDA
personnel evaluated products containing AHAs from retail stores in the
Washington, DC, area and compiled a survey of label claims made for the
products (Reference 2). AHA-containing products are labeled with a
variety of claims for benefits of use to the skin, including
exfoliating, moisturizing, cleansing, wrinkle reducing, softening,
smoothing, texture improvement, increased firmness and elasticity,
improvement of photodamage, skin protection, effects on skin structure
and composition, soothing, healing, renewing, revitalizing, scar
reduction, anti-aging, anti-acne, skin tone evening, skin lightening,
skin conditioning, astringent, and oxygen boosting. Most products are
labeled with several claims.

FDA's surveys found that, in 64 consumer products, exfoliation claims
were the most common and were made on 50% of the products. The next most
common claims were for anti‑aging (38%), wrinkle and line reduction
(38%), and softening and smoothing (36%). For salon products,
exfoliation claims also were the most common and were made on 64% of the
33 products surveyed. The next most common claims also were for
anti‑aging (18%), wrinkle and line reduction (15%), and softening and
smoothing (15%).

The survey suggests, therefore, that only half of the AHA-containing
products on the market have an intended use as an exfoliant, as
determined by the presence of "exfoliant" claims on the product
labeling. Even some salon products containing high levels of AHAs did
not specify "exfoliation" as an intended use.

The evidence reviewed so far by FDA suggests the possibility of sunburn
from any AHA-containing product and not merely products labeled for
exfoliant use. Therefore, FDA suggests a statement such as the "Sunburn
Alert" be included in the labeling for all AHA-containing products.

**Statutory Basis**

21 U.S.C. 362(a) provides that a cosmetic is misbranded if its labeling
is false or misleading in any particular. 21 U.S.C. 321(n) amplifies
what is meant by "misleading." This section states that in determining
whether labeling is misleading, an individual should take into account
the extent to which the labeling fails to reveal facts material to
results which may occur from the use of the product as it is labeled or
customarily used (*see also* 21 CFR 1.21).

Based on evidence reviewed so far (including safety reviews conducted by
the CIR Expert Panel, the AHA Review Committee, and FDA), FDA currently
believes that topically applied cosmetic products containing AHAs may
increase skin sensitivity to the sun while the products are used and for
up to a week after use is stopped, and that this increased skin
sensitivity to the sun may increase the possibility of sunburn. FDA
believes that this conclusion may be a material fact that manufacturers
should disclose to users under 21 U.S.C. 362(a), 21 U.S.C. 321(n), and
21 CFR 1.21. Accordingly, FDA believes that if manufacturers inform
users of AHA-containing products about the potential for increased skin
sensitivity to the sun and particularly the possibility of sunburn, and
what steps a user may take to avoid such consequences, this will help
avoid the potential that the products are misbranded under 21 U.S.C.
362(a) and 21 U.S.C. 321(n).

**Draft Guidance**

CTFA's citizen petition requested that FDA issue a regulation in part
701 of the CFR (21 CFR Part 701Cosmetic Labeling) establishing a sun
alert labeling statement for AHA-containing cosmetic products. FDA is
issuing this draft guidance entitled "Guidance for Industry: Labeling
for Topically Applied Cosmetic Products Containing Alpha Hydroxy Acids
as Ingredients" rather than a proposed regulation.

FDA is issuing this draft guidance pending the results of the NCTR study
because the agency believes interim action is warranted to recommend
that manufacturers label topically applied cosmetic products that
contain AHAs to alert consumers of the need to use sun protection when
using these products. After assessing the results of the
photocarcinogenicity study and the effectiveness of any final guidance,
the agency intends to determine if additional agency action is
appropriate.

**Electronic Access**

Copies of this draft guidance are available on FDA's website at
[http://www.cfsan.fda.gov/\~dms/guidance.html]{.underline}. Submit
electronic comments to
[http://www.fda.gov/dockets/ecomments]{.underline}.

**REFERENCES:**

1.Yates, R.L., and D.C. Havery, "Determination of Phenol, Resorcinol,
Salicylic Acid and α-Hydroxy Acids in Cosmetic Products and Salon
Preparations," Journal of Cosmetic Science, vol. 50, pp. 315‑325, 1999.

2\. Barrows, Julie N., Memorandum to the Administrative File, "Guidance
for Industry: Labeling for Topically Applied Cosmetic Products
Containing Alpha Hydroxy Acids as Ingredients," Office of Cosmetics and
Colors, CFSAN, FDA, September 12, 2002.

3\. Andersen, F. A., Ed., "Final Report on the Safety Assessment of
Glycolic Acid, Ammonium, Calcium, Potassium, and Sodium Glycolates,
Methyl, Ethyl, Propyl, and Butyl Glycolates, and Lactic Acid, Ammonium,
Calcium, Potassium, Sodium, and TEA-Lactates, Methyl, Ethyl, Isopropyl,
and Butyl Lactates, and Lauryl, Myristyl, and Cetyl Lactates,"
International Journal of Toxicology, vol. 17, supplement 1, pp. 1-241,
1998.

4\. FDA, Memoranda of Meetings of AHA Review Committee, May 6, 1997, and
February 12, 1997, and index of reviewed information.

5\. Hawk, J. L. M., Ed., "Photodermatology," Arnold Publishers, Chapters
4, 6, and 7, pp. 43-52 and 69-102, 1999.

6\. DeGruijl, F. R., J. B. VanDerMeer, and J. C. VanDerLeun, "Dose-Time
Dependency of Tumor Formation by Chronic UV Exposure," Photochemistry
and Photobiology, vol. 37, pp. 53-62, 1983.

7\. Strickland, P. T., et al., "Quantitative Carcinogenesis in Man:
Solar Ultraviolet B Dose Dependence of Skin Cancer in Maryland
Watermen," Journal of the National Cancer Institute, vol. 81, pp.
1910-1913, 1989.

8\. Forbes, P. D., et al., "Simulated Stratospheric Ozone Depletion and
Increased Ultraviolet Radiation: Effects on Photocarcinogenesis in
Hairless Mice," Cancer Research, vol. 42, pp. 2796-2803, 1982.