the first sunscreen product was developed in 1928, it was not until the 1940s
that the FDA began to regulate these products.1 On November 21,
1997, Congress mandated that the FDA, in accordance with the Food and Drug
Administration Modernization Act of 1997 (FDAMA), regulate the prevention and
treatment of sunburn as it does with all other OTC medications. Since then,
regulations for testing and labeling have been set forth by the FDA for
ultraviolet B (UVB) protection in sunscreen products. Only recently has the
FDA proposed rules and regulations about ultraviolet A (UVA) protection in
It is commonly known that the
sun's ultraviolet radiation causes complications ranging from skin aging,
photodermatoses, photosensitivity, and erythema to, most importantly, skin
cancer.1-4 The sun radiates UVA, UVB, and ultraviolet C (UVC) rays.
The ultraviolet wavelengths differ among A, B, and C with lengths of 320-400,
290-320, and 200-290 nanometers, respectively.5,6 Darkening of the
skin or tanning is caused by both UVA and UVB radiation. The longer
wavelengths associated with UVA penetrate the dermis more deeply, causing skin
aging and prolonged pigmentation. Recently, UVA radiation has been further
classified as UVAI (340-400 nm) and UVAII (320-340 nm). Ultraviolet B does not
penetrate the dermis as deeply as UVA due to its shorter wavelengths; however,
it does cause significant sunburn.2,6 Shorter-wavelength UVAII
radiation has also been shown to cause sunburn like UVB. Longer-wavelength
UVAI has been known to cause skin damage as well as increase the risk of skin
tumors.7-9 The ozone absorbs 100% of short-wave radiation, such as
UVC, so the effects of UVC on the skin are negligible. The ozone also absorbs
a high portion of UVB, whereas it absorbs very little of UVA due to the longer
The three most common forms of
skin cancer include basal cell carcinoma, squamous cell carcinoma, and
melanoma. Basal cell and squamous cell carcinoma are responsible for close to
90% to 95 % of all forms of skin cancer. These types of cancer mostly involve
only the epidermis and dermis layer with rare metastasis to other organs.
Melanoma, although rare, may result in metastasis to other organs and is much
more fatal compared to nonmelanoma cancers.2,3 Risk factors for
developing skin cancer include light natural skin color, family and personal
history of skin cancer, blue or green eyes, blond or red hair, certain types
and large number of moles, and exposure to the sun. Damage to DNA causing
different forms of skin cancer has been linked primarily to UVB radiation;
however, UVA has also been shown to cause DNA damage as well as
immunosuppression leading to forms of skin cancer such as melanoma.2,3,10
Current Sun Protection
The FDA and the
American Academy of Dermatology (AAD) recommend nonpharmacologic and
pharmacologic interventions to protect the skin from the sun. Wearing
protective clothing such as wide-brimmed hats, long-sleeved shirts, and
dark-colored clothing, in addition to sunscreen, has been the gold standard to
prevent sun-induced complications. There are currently two classes of
sunscreen agents: inorganic and organic. Inorganic agents are also referred to
as physical blockers. These agents include zinc oxide, titanium
dioxide, and red petrolatum. The physical blockers scatter and reflect
radiation. Though these agents are very well tolerated, due to the opaqueness
of the topical agent they are very unpleasant aesthetically, leaving a
white-colored residue layer. Micronized forms of inorganic agents helped
reduce the whitish residue; however, they also caused less scattering of
light. Prior to micronization, inorganic agents were able to block long
wavelengths such as UVA. After micronization, only shorter wavelengths such as
UVB could be reflected.2,6 Organic agents differ from inorganic
agents in that they do not reflect radiation but rather absorb it. They absorb
the UV radiation and convert it to heat energy by means of electron
excitation. The organic agents can further be classified by whether they
protect against UVA or UVB. TABLE 1 lists the FDA-approved agents for
both the inorganic the organic agents and their spectrum of activity against
Though there are a number of
sunscreen agents that protect against UVA in addition to UVB, consumers would
only be aware of this if they knew the ingredients listed inTABLE 1. On
each sunscreen bottle, the FDA has regulated that a sunburn protection factor
(SPF) be labeled.11,12 The SPF is tested in humans by exposing a
small portion of unprotected skin to short wavelengths for up to 24 hours or
until sunburn occurs. Later, the same radiation is exposed to the same
individual; however, this time the subject wears sunscreen. If it took 50
seconds for a subject to acquire sunburn with no sun protection and 500
seconds with the sunscreen applied, the SPF would be 500 divided by 50,
equaling an SPF of 10. Since sunburn is mostly caused by short-wavelength UVB
radiation, the SPF test is primarily testing for protection against UVB.
Ultraviolet A causes more long-term effects such as wrinkles and skin aging.
Compared to UVB endpoints, such as sunburn used in SPF testing, there are no
acute end points associated with UVA exposure. This makes testing for
protection against this type of radiation rather difficult.13,14
Currently, consumers are
accustomed to seeing an SPF factor on all sunscreen products (FIGURE 1
). The higher the SPF value, the more protection against sunburn is expected.
As stated earlier, the SPF test only measures UVB radiation, not UVA
radiation. On August 27, 2007, the FDA proposed regulations on how to test for
UVA radiation and how to label sunscreen products to familiarize consumers
with the effectiveness of these products.
The FDA is
requiring sunscreen manufacturers to undergo in vitro and in vivo studies to
test the amount of UVA protection of their products. The in vitro study
determines the ratio of UVAI absorbance to the total of UVB and UVA
absorbance. The in vivo method uses a test similar to the SPF test known as
the Persistent Pigment Darkening (PPD) test.15,16 As opposed
to using sunburn as the end point, which is done in the SPF test, pigment
darkening is used in the PPD test. Since pigment darkening is not the only
clinical outcome associated with UVA radiation, using this end point is not
the only reliable test to accurately identify protection from UVA radiation.
The FDA recognizes this limitation and therefore suggests using both the in
vivo and in vitro tests to assess the protection against UVA radiation in
sunscreen products. The ratings of UVA protection will not be based solely on
a ratio as with UVB protection. After compiling the data from the in vivo and
in vitro data, the FDA will classify sunscreen products as offering Low,
Medium, High, and Highest protection against UVA radiation. One star will be
given for the Low, two stars for the Medium, three stars for the High, and
four stars for the Highest UVA protection categories. FIGURE 1 shows
the current labeling of sunscreen products and the new FDA-proposed labeling.
Although no standardized test
for UVA protection has been widely accepted, other regulatory boards, such as
the Japanese Cosmetic Industry Association and the European Union Commission,
have endorsed the PPD testing method. The AAD also supports the PPD test.
18 Nash et al showed many of the disadvantages to this test in in vivo
testing.14 The PPD test exposes the human subject to only UVA
radiation, as opposed to the entire UV spectrum. They showed that filtering
the radiation so that the subjectÜ was exposed to only UVA altered the
absorption of the radiation. This makes the PPD test very inapplicable to a
consumer who will go out in the sun exposed not only to UVA radiation but to
other types of radiation. In addition to the PPD test's inaccuracies, its high
cost and the expertise required to administer it makes the test must less
desirable for sunscreen manufacturers.14 The FDA estimates a
one-time cost of $2,200 per sunscreen product to test for UVA protection. In
addition to testing, manufacturers must also comply with labeling
requirements, as seen in FIGURE 1. The estimated costs for relabeling
sunscreen products are $7,600 per product. The total estimated costs for
relabeling and testing for all sunscreen products is estimated by the FDA to
total $53 million.12
Although UVA testing and
relabeling is one of the biggest changes the FDA is currently proposing, the
agency is also proposing some changes to UVB labeling. Currently, the maximum
SPF value assigned to a sunscreen product is 30+. The FDA is proposing to
increase that number to 50+ for sun-sensitive individuals requiring more
protection. In addition, the FDA is proposing to change the term SPF or "
sun protection factor" to "sunburn protection factor."12
TABLE 2 shows a summary of the FDA-proposed changes to OTC sunscreen
The Pharmacist's Role
With all of the
changes to sunscreen labeling and testing being proposed, it is especially
important for pharmacists to understand how this impacts medications that
commonly cause photosensitivity. Although it is not all-inclusive, a list of
common medications that cause photosensitivity reactions are listed in
TABLE 3.19-23 Photosensitivity reactions can be classified as
phototoxic or photoallergic. Phototoxic reactions cause an increase
of UV radiation absorption in the skin. Photoallergic reactions are immune
mediated and cause changes to the drug, causing a hypersensitivity-like
reaction to the medications.20 These medications are affected by
all types of UV radiation to which the skin is exposed, including UVA and UVB.
To prevent many of these photosensitivity reactions, it is important for
consumers to use broad-spectrum sunscreen products. The proposed ruling by the
FDA will help consumers identify which sunscreen products are optimal for
preventing drug-induced photosensitivity reactions when using offending
Though the accuracy of the
testing for UVA protection is still under scrutiny, the proposed labeling will
help consumers identify sunscreen products that more effectively protect them
against UV radiation complications. This may also entice researchers to
further evaluate more accurate testing methods for UVA radiation in human
subjects. The AAD has supported many of the changes proposed by the FDA, which
reiterates the importance of compliance to sunscreen use in addition to
picking the right sunscreen product. Pharmacists will be key players in
helping consumers identify the appropriate sunscreen products needed when the
changes in labeling do occur sometime later this year.
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ultraviolet radiation, sunscreens, and photo-induced dermatoses. Dermatol
2. Lautenschlager S, Wulf HC,
Pittelkow MR. Photoprotection. Lancet. 2007;370:528-537.
3. Epstein FH. The pathogenesis of
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4. Fisher GJ, Wang ZQ, Datta SC, et
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5. Matts PJ. Solar ultraviolet
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6. Palm MD, O'Donoghue MN. Update on
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7. Lavker RM, Veres DA, Irwin CJ, et
al. Quantitative assessment of cumulative damage from repetitive exposures to
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pigment darkening (PPD) method (Part 2). Photodermatol Photoimmunol
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18. Baker DR. Letter to the
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CFR 21: 352. www.aad.org/pm/temp/_doc/ResponseToFDA.pdf.
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