Dermatologic Therapy, Vol. 25, 2012, 223–228
Printed in the United States · All rights reserved
© 2012 Wiley Periodicals, Inc.
DERMATOLOGIC THERAPY
ISSN 1396-0296
INTRODUCTION
Cosmetics, categories, and
the future
Zoe Diana Draelos
Department of Dermatology, Duke University School of Medicine, Durham,
North Carolina
ABSTRACT: Cosmetics is an interesting unregulated category of over-the-counter products designed to
enhance appearance and skin health. The coloring agents used in cosmetics are regulated along with
their preservative constituents. New understandings of skin physiology have allowed cosmetics to
advance beyond appearance issues into the functional arena. Cosmeceuticals is an unrecognized term
from a regulatory perspective that conveys the new cosmetic formulations ability to improve skin health.
KEYWORDS: cosmetics, cosmeceuticals, antiaging
The category defined as cosmetics represents an
interesting grouping of products full of innovation
and complex formulations not subject to the
restrictions of pharmaceuticals. This has allowed
more new developments and an expansion of
product categories in the cosmetics realm that has
far outstripped the pharmaceutical realm-making
cosmetics an extremely interesting field to the dermatologist. This issue of dermatologic therapy is
aimed at presenting the latest and most interesting
information in cosmetics that is important to the
daily practice of dermatology. This introductory
article will set the stage for the reader to eagerly
anticipate the timely information included in this
issue.
Product categories
Products of interest to the dermatologist can be
divided into cosmetics, over-the-counter (OTC)
Address correspondence and reprint requests to: Zoe Diana
Draelos, MD, Consulting Professor, Department of
Dermatology, Duke University School of Medicine, 2444 North
Main Street, High Point, NC 27262, USA, or email
zdraelos@northstate.net.
drugs, and drugs. Drugs are highly regulated and
must receive FDA approval prior to consumer sale.
Since the dermatologist is very familiar with the
drug regulatory environment, no more discussion
will be devoted to this topic. The OTC drug realm
may be less familiar to the dermatologist, which
includes such products as antiperspirants, acne
treatments, skin protectants, and sunscreens.
These products do not go through an FDA approval
process because their formulations are based on
monographs that specify the active ingredients
that can be included and the concentration of
these ingredients. Any product that lists an active
ingredient on the packaging is considered an OTC
drug. There is less regulation of the vehicle that
delivers the active ingredient because this is typically a cosmetic type formulation. For this reason,
most OTC drugs in a given category have a somewhat similar formulation.
While cosmetics do not have monographs or
other literature governing their formulation, the
coloring agents that can be incorporated are
strictly controlled. This control was specified as
part of the US Food, Drug, and Cosmetic Act of
1938 (1). The only uncontrolled category of products is actually soap. All other skin care products
and cosmetics are covered by some regulatory
223
Draelos
document except cleansers. The regulation of
cleansers was not undertaken as there was concern
that this would increase the cost of these products
and have a detrimental effect on hygiene and infection control.
Control of the cosmetics industry began with
the recognition that some products were tainted
with lead, mercury, and arsenic. One of the most
common bleaching creams, known as skin whitening creams at the time, introduced in the 1930s
contained mercury and another contained arsenic.
It was the introduction of these dangerous products that led the federal government to recognize
the need to protect the common good from these
hazards. This type of protection is very important,
as the quickest way to whiten skin is to induce a
state of anemia, which is how some of the skin
whitening products worked.
The earliest cosmetics
The earliest cosmetics were not actually creams,
liquids, or gels. They were cloth patches designed to
cover facial blemishes known as beauty patches.
These patches were developed and became popular
in the 1600s to cover permanent facial scars left on
those in Europe who survived smallpox epidemics.
These were black silk or velvet pieces shaped like
stars, moons, and hearts that were carefully placed
about the face. Patch boxes, the forerunner of the
mirrored facial compact, were carried everywhere
to keep replacements handy should a patch fall off
in public (2). The wearing of patches evolved into an
unspoken language: a patch near a woman’s mouth
signaled flirtatiousness, a patch on a woman’s right
cheek indicated she was married, a patch at the
corner of a woman’s eye announced smoldering
passion, etc.
From these early facial ornaments to cover facial
scarring, a theatrical product was developed known
as French White (3). This cream was a big improvement over dusting the skin with loose powder and
was used to whiten the skin and cover scarring on
the face, neck, and arms. It consisted of white
powder dissolved in a liquid vehicle that dried to a
thin film over the body, but was easily removed with
rubbing and sweat discoloring clothing and making
a mess. In order to increase the ability of the cosmetic to stay on the skin with sweating, “grease
paints” were developed with pigments and fillers
suspended in oily vehicles for theatrical use. An
adaptation of these early grease paints reach high
popularity in the consumer market when Max
Factor developed cake makeup, which he patented
224
Table 1. Coloring agents used in cosmetics
Iron oxides
Titanium dioxide (alone, or combined with mica)
Copper, aluminum, and silver powder
Ultramarine blue, violet, and pink
Manganese violet
Carmine
Chrome oxide and hydrate
Iron blue
Bismuth oxychloride (alone, or on mica or talc)
Mica
in 1936 (4). This product provided excellent
coverage, a velvety look, and added facial color. The
consumer cosmetics category was born and has
expanded tremendously over the last 75 years.
Cosmetics safety and color agents
Cosmetics safety is very important especially
around the eyes and lips. These are two areas commonly adorned by colored cosmetics. Eyelid cosmetics have been used by women and men since
4000BC when green malachite powder was heavily
applied to the upper and lower eyelids accompanied by dark kohl eyeliner paste composed of powdered antimony, burnt almonds, black copper
oxide, and brown clay ocher. Ground beetle shells
were added to produce glitter. However, now the
coloring agents that can be used around the eyes
are strictly regulated. No coal tar derivatives can be
used, only approved purified natural colors or inorganic pigments as set forth in the Food, Drug, and
Cosmetic Act of 1938 are allowed (1). Table 1 lists
the coloring agents that are government approved.
The same types of restrictions also apply to
eyelash cosmetics, more commonly known as mascaras. Coal tar derived colors are also prohibited.
Therefore, mascara colorants must be selected
from vegetable colors or inorganic pigments and
lakes. Colors employed include iron oxide to
produce black, ultramarine blue to create navy and
umber (brown ochre) or burnt sienna (a mixture
of hydrated ferric oxide with manganic oxide) or
synthetic brown oxide to create brown (5).
The safety of the coloring agents used in lipsticks
has received a great deal of attention due to the
inevitable entry of lipsticks into the mouth. The
Food and Drug Administration divides certified
colors into three groups: Food, Drug, and Cosmetic
(FD & C) colors, Drug & Cosmetic (D&C) colors, and
External Drug & Cosmetic colors. Only the first two
groups can be used in lipsticks. The External Drug &
Cosmetics, categories, and the future
Cosmetic colors can only be used in locations where
they are not likely to enter the mouth (6).
There has been some popular press about the
contamination of lipstick pigments with lead. This
could be perceived as an issue on the surface, but is
a nonissue when investigated more deeply. The red
pigments used in lipsticks may contain extremely
minute amounts of lead, but nowhere near the
amount found in old paints where breathing the
lead dust or eating the lead-containing paint result
in heavy metal poisoning. The consumer would
have to eat thousands of tubes of lipstick annually
to achieve lead poisoning from lipsticks. As with
everything, it is a matter of degree. Persons who eat
large quantities of red lipstick should be careful.
pensed from a jar affixed with a one-way valve top.
This valve prevents oxygen and anything outside
from entering the jar.
In many ways, preservatives are the consumers’
best friend insuring product stability and longevity
until the jar is emptied. Preservatives are listed on
the ingredient disclosure usually within the last
one to three ingredients. Since ingredients are
listed in order of concentration, this means that
the preservative is the ingredient present in lowest
concentration. It interesting to think that man has
fought over salt and spices to preserve food in the
pre-refrigeration era and many groups are now
trying to restrict preservation of cosmetics.
Safety testing of cosmetics
Preservatives and cosmetics safety
Perhaps the biggest area of controversy surrounds
the use of preservatives in cosmetics. Animals that
are fed large quantities of preservatives typically do
not enjoy a long life. This is not surprising as the
primary role of antimicrobial preservatives is to
destroy bacteria and prevent contamination. The
risk of transferring infection from cosmetics contamination is much bigger than the risk of using
minute amounts of the preservative on the skin.
Most people do not drink their facial foundation by
the bottle, which is how animal testing is performed to determine safety and carcinogenicity.
Furthermore, the risk of contaminating cosmetics
by sticking dirty fingers into the jar or transferring
an ocular infection from one eye to the other via a
mascara wand is much larger.
There has been a movement as of late to eliminate preservatives from cosmetics, however, it
should be recognized that there is no such thing as
a preservative-free commercially made cosmetic.
Most cosmetics are not used until 3–6 months or
longer after they have left the manufacturing facility. This means some form of preservation is necessary. If the product does not contain water, it can
be preserved with lower preservative levels, since
water is necessary for microbial growth. Many
products that label themselves as preservative free
actually contain preservatives, but the ingredient
falls under a different category. For example, phenoxyethanol has a lovely rose scent and may be
used as a fragrance ingredient when in reality is it a
preservative. Many spices, such as clove essences,
can be used for a combination of fragrance and
preservation. Finally, it is also possible to lower the
preservative concentration by special packaging.
Many of the newer facial foundations are dis-
Why have there been so few instances of adverse
events associated with the use of cosmetics?
Because cosmetics are safe. Think of how many
people use large numbers of cosmetics on a daily
basis and how few problems arise. Why are cosmetics so safe? Because large cosmetic manufacturers
spend tremendous resources formulating safe
products, searching for quality ingredients, designing packaging to maintain product purity, and
writing labeling to insure that consumers use the
product properly. Most reputable manufacturers
do safety testing on their products prior to marketplace introduction. This safety testing may include
eye instillation, repeat insult patch testing, cumulative irritancy testing, and safety-in-use testing.
Many companies also test their products on sensitive skin subjects, including those with a variety of
dermatologic conditions such as eczema, rosacea,
atopic dermatitis, etc.
Why are so many resources devoted to cosmetic
testing? Because a product that causes problems
in the marketplace tarnishes the reputation of a
company and erodes consumer confidence. This
means that every product they manufacture is
subject to question and results in lost sales and
lower revenues. No company wants to lose its reputation on a problematic product. It is perhaps the
power of the consumer marketplace that drives
cosmetic safety, which is an inherent advantage of
an open competitive marketplace.
Cosmeceuticals and skin aging
One of the subcategories of cosmetics that has
received much dermatologic attention is cosmeceuticals. The FDA does not recognize cosmeceuticals as a category and simply views them as
225
Draelos
cosmetics. While cosmeceuticals are considered
quasi-drugs in Japan, it is unlikely that this category will receive governmental recognition in the
United States. Cosmeceuticals have been called by
many names including active cosmetics and functional skin care. For the most part, they are moisturizers that have additional ingredients added to
provide benefits beyond traditional skin creams;
however, they cannot make more robust claims.
The most commonly added ingredients are botanicals, marine extracts, and vitamins many of which
function either directly or indirectly as antioxidants. Since oxidation is a key event in aging that
can be easily understood by consumers, this is a
good target for product claims.
Many cosmeceuticals target the effect of oxygen
on the human body, which is a relatively new
element to our planet with its origin about 2 billion
years ago when water-splitting microorganisms
first released oxygen to create our atmosphere. The
development of plants engaged in photosynthesis
further increased the atmospheric oxygen, some of
which ended up as ultraviolet protective ozone.
The oxygen molecule possesses two unpaired electrons, which makes it a diradical. When a molecule
accepts an electron, it undergoes a reduction reaction, while when it loses an electron it undergoes
an oxidation reaction. It is the univalent reduction
of oxygen, or the addition of one electron at a time,
that produces reactive oxygen species. These reactions are diagramed below:
Oxygen + one electron = Superoxide (O−2 )
Superoxide + one more electron
= Hydrogen peroxide (H 2O2 )
Hydrogen peroxide + one more electron
= Hydroxyl radical (OH )
Hydroxyl radical + one more electron + hydrogen
= Water (H 2 O)
Only the superoxide and hydroxyl radical are
considered free radicals. While hydrogen peroxide
is a reactive oxygen species, it is not a free radical,
and water, of course, is completely stable. There is a
fourth type of reactive oxygen species known as
singlet oxygen. These are the targets that topical
and oral antioxidants attempt to quench preventing DNA, protein, and lipid damage that results in
low grade inflammation immediately, aging in the
long term, and possibly carcinogenesis if the DNA
damage is sufficiently severe.
The hydroxyl radical produces most of the cellular oxidative damage to nuclear DNA. Hydroxyl
radicals are able to interact with the purine and
226
pyrimidine bases damaging the DNA code, but
repair mechanisms are in place to remove the
damaged bases. Cellular damage also occurs when
oxygen is irradiated with ultraviolet absorbing the
energy and changing its molecular configuration.
Singlet oxygen is created when one of the unpaired
electrons is elevated to a higher energy level and its
spin number is inverted. This allows the singlet
oxygen to damage proteins and the double bonds
in cell wall lipids creating oxidative stress.
Oxidative stress occurs when body structures
are damaged over time with repeated insults,
which cumulatively are labeled as aging. For
example, superoxide attacks unsaturated fatty
acids in the cell membrane damaging its integrity.
When unsaturated fatty acids are oxidatively
damaged in foods, the food is said to be rancid.
Aging is basically rancidity of the human body.
When the fatty acids are damaged in the body, an
amorphous yellow material known as lipofuscin is
produced. Lipofuscin can accumulate in the skin
and accounts for the dusky yellow hue characteristic in the facial skin of heavy tobacco smokers. This
lipid peroxidation commonly occurs in the essential fatty acids of the body, such as linolenic acid,
because it possesses three double bonds. Malonyldialdehyde, abbreviated MDA, is a marker of lipid
peroxidation, and systemic levels can be used to
determine the amount of oxidative stress the body
has endured.
The body must protect itself from oxidative
stress for survival. As a matter of fact, persons who
age more slowly may have better oxidative stress
protection than those who age rapidly. The endogenous mechanisms for oxidative stress protection
are summarized in Table 2. Targeting this type of
oxidative stress is the goal of many cosmeceuticals.
The future of cosmetics and
cosmeceuticals
Even though oxidative damage is currently the key
target of many anti-aging cosmetics and cosmeceuticals, new genetic technologies are allowing
the identification of new targets. One new antiaging field is genomics, which may provide insight
into why some age better than others, even though
they may have sustained significant UV exposure.
Each human possess a double genetic code, one
derived maternally and the other derived paternally. Both codes cannot be simultaneously
expressed, thus each individual is a mosaic. This
mosaicism may explain how appearance and
aging may differ between persons. Why do some
Cosmetics, categories, and the future
Table 2. Endogenous oxidative stress protection
Antioxidant enzymes
1. Superoxide dismutase: Converts superoxide to peroxide and oxygen
2. Catalase: Converts hydrogen peroxide to water and oxygen
3. Glutathione peroxidase: Converts hydrogen peroxide to water and oxygen
Lipid soluble antioxidants
1. Tocopherol (Vitamin E): Quenches hydroxyl radical
2. Beta carotene (Vitamin A): Quenches singlet oxygen
3. Ubiquinol, ubiquinone: Quenches hydroxyl radical and singlet oxygen
Water soluble antioxidants
1. Ascorbid acid (Vitamin C): Regenerates vitamin E, may react directly with other ROS
2. Glutathione: Reacts with hydroxyl radical, part of glutathione peroxidase system
3. Uric acid: Quenches singlet oxygen, hydroxyl radical inhibits xanthine oxidase, which forms superoxide
Fitzpatrick skin type I individuals experience frequent actinic keratoses and basal cell carcinomas,
while others with relatively similar lifetime sun
exposure have no precancer or cancer history?
There must be something different about how the
melanin dissipates oxidative insults protecting the
cellular DNA in the fair-complected person with
minimal sun damage. Genomics can be used to
gain a better understanding of the skin protective
mechanisms and how products might be designed
to enhance defective mechanisms.
Genomics also provides an understanding of
how young skin is different from aging skin on a
cellular level. Dermatologists readily recognize the
smooth even-colored skin of youth that visibly
contrasts with the dyspigmented rough wrinkles
skin of photoaging. Gene analysis of sun-protected
young skin, sun-protected mature skin, sunexposed young skin, and sun-exposed mature skin
has been valuable in understanding the changes
in gene expression with aging. The upregulation
and downregulation of collagenase, interleukins,
matrix metalloproteinases, and prostaglandins has
helped to better understand intrinsic and extrinsic
aging. This type of genomic analysis provides a cellular understanding of aging, creating targets for
cosmeceutical ingredients. Gene families for aging
are being defined that form the basis for skin
appearance.
Finally genomics provides the ability to test new
ingredients for their value in photoaging. Once the
targets have been identified, genomics can be used
to investigate the effect of various topical agents on
aging skin. For example, engineered peptides can
be placed in fibroblast cultures to determine their
ability to modulate fibroblast functioning. One
family of peptides that was tested in this manner
is known as signal peptides, which were found to
stimulate collagen, elastin, fibronectin, proteoglycan, and glycosaminoglycan production creating
the appearance of younger looking skin. This was
determined in part by analyzing the substances
found in the culture plate after exposure to the signaling peptide with a gene chip. The gene chip
allowed the rapid identification of thousands of
cellular changes, which were analyzed through
bioinformatic computer programs. While gene
chip genomic analysis can be used to eliminate
ineffective or skin damaging ingredients, it cannot
be used to guarantee clinical efficacy. In this case,
genomics provides a valuable research tool.
Without the gene chip, it would take years to screen
through libraries of botanical extracts to determine
the most promising ingredient candidates.
Summary
This introduction to the cosmetics update issue of
Dermatologic Therapy has provided an overview of
some key concepts. It has investigated the regulatory and safety issues pertinent to cosmetics.
Further, it has discussed the category of cosmeceuticals which represent functional cosmetics largely
aimed at skin aging prevention and improvement.
While antioxidants presently abound as the active
ingredients in cosmeceuticals, new targets are
being identified through genomic analyses. The
articles in this issue are intended to update the dermatologist on key developments in the cosmetics
realm.
References
1. Lanzet M. Modern formulations of coloring agents: facial and
eye. In: Frost P, Horowitz SN, eds. Principles of cosmetics for
the dermatologist. St. Louis, MO: C. V. Mosby Company, 1982:
138–139.
2. Panati C. Extraordinary origins of everyday things. New York,
NY: Perennial Library, Harper & Row, 1987: 225–226.
227
Draelos
3. Schlossman ML, Feldman AJ. Fluid foundations and blush
make-up. In: deNavarre ed MG, ed. The chemistry andmanufacture of cosmetics, 2nd ed. Wheaton, IL: Allured Publishing
Corporation, 1988: 741–765.
4. Wells FV, Lubowe II. Cosmetics and the skin. New York, NY:
Reinhold Publishing Corporation, 1964: 141–149.
228
5. Wilkinson JB, Moore RJ. Harry’s cosmeticology, 7th ed. New
York, NY: Chemical Publishing, 1982: 341–347.
6. deNavarre MG. Lipstick, in the chemistry and manufacture
of cosmetics, 2nd ed. Wheaton, IL: Allured Publishing
Corporation, 1975: 778.