Therapeutic Sun Care A Guide to Light Protection · 2016. 4. 27. · II. The Sun’s Effect On Your...

Therapeutic Sun CareA Guide to Light Protection

Fallene Ltd.

1

I. Preface

II. The Sun’s Effect on the Skin

III. The Light Spectrum

IV. SPF Is Not Enough

V. Skin Cancer

VI. Vitamin D

VII. Photosensitivity

VIII. The Chemistry of Sunscreen IX. Fallene, Ltd. and Full Spectrum Sun Protection

X. Commonly Asked Questions

Appendix A: How SPF is Determined by OTC Monograph Testing

Appendix B: Prescription Drugs and Photosensitivity

Glossary of Terms

References

Foot Notes

Notes

TABLE OF CONTENTS

Table of Contents

3

If they think about their skin at all, many people regard it only as a surface layer, an outer shell that keeps out the elements. While it is true that normal, healthy skin is a barrier and does protect us from injury, it is also the largest organ of our bodies; one that is not impervious to harm. Healthy skin is critical to maintaining good health, and sun protection is critical to preserving healthy skin.

This booklet was created to present information that is crucial to a thorough understanding of sun protection. It examines the commonly held notion that “SPF 30 is enough” and clarifies why that statement is both misleading and medically unfounded; explains how sunscreens work to protect our skin; and explains why protecting our skin is a vital factor in staying healthy.

In 1989 two medical professionals, one a physician and the other a pharmaceutical chemist, founded Fallene, Ltd. with a very straight forward goal: to produce the most complete, full-spectrum sunscreen available, something that would work for light-sensitive individuals, particularly those patients with photosensitivity and skin cancer. Achieving that goal required a thorough understanding of how the sun’s radiation affects unprotected skin, what ingredients the FDA has approved for use in sunscreen and how they worked, how those ingredients reacted when exposed to sunlight, and, finally, what those reactions meant for skin health. Armed with this knowledge, they developed the most advanced light-protective, full-spectrum sunscreen system possible and combined it with multiple cellular protectants. The result was a complete system that both reduced the impact of the sun’s photodamaging radiation on the skin and acted as an aid to reverse skin damage at the cellular level.

Total Block® was introduced to the dermatologic community in 1994. Since that time, Fallene has grown to offer a family of products, all of which offer the most complete full-spectrum light protection available. The current product line features a non-comedogenic SPF 65 sunscreen, an SPF 60 tinted foundation, and four mineral-based products: an SPF 58 water-resistant formula, an SPF 45 lip balm, SPF 35 20% zinc oxide formulation, and two very water-resistant products with an SPF 40, all of which are free of chemical sunscreens and use no active ingredients other than titanium dioxide and/or zinc oxide.

Fallene’s products are recommended by physicians and skin care professionals around the world. They are used not only by medically photosensitive individuals, but also by those who are concerned about maintaining their skin’s healthy appearance and, more importantly, promoting the integrity of their immune system.

Sun protection matters, and SPF 30 is not enough. The following pages explain why.

I. PREFACE

I. Preface

5I. Preface

The Facts of Light I:

• SunElevation: The higher the sun is in the sky, the higher the UV radiation level.• Latitude:UV radiation levels increase with proximity to equatorial regions.• CloudCover:UV radiation penetrates clouds. Levels are highest when the sky is clear, but

even with cloud cover, they can be high. Skin is susceptible to sunburn even when the sun’s rays are not visible.

• Altitude: The thinner atmosphere at higher altitudes absorbs less UV radiation.• Ozone:Ozone absorbs some UV radiation that would otherwise reach the earth’s surface.• Groundreflection:Grass, soil & water reflect less than 10% of UV radiation; fresh snow

reflects as much as 80%; dry beach sand about 15%; sea foam about 25%.• UVA radiation can penetrate glass. • Even casual exposure to sunlight, while driving, walking to the store, taking an outdoor

break is incremental and contributes to the cumulative lifetime radiation exposure that results in skin damage.

• The UV index, developed by the National Weather Service and the Environmental Protection Agency, forecasts the amount of UV expected to make it to the earth’s surface when the sun is highest in the sky. The higher the index, the faster the UV radiation will cause damage to the skin and eyes.

• 1 in 5 Americans will develop skin cancer in their lifetime as a direct result of sun exposure.• Summer is not the only time to be aware of the sun’s impact. Sun can cause significant

damage even during the winter months. • When skin absorbs UV radiation from the sun, the melanocytes, the skin cells that produce

melanin (pigment), enlarge, increase, and melanin is transported to cells of the outer skin, giving the sun damaged skin a leather-like appearance.

• Some damage caused by the sun’s UV radiation results in permanent destruction of the skin’s supporting structure; premature wrinkling; precancerous skin lesions; drug reactions; eye damage; dilated blood vessels; sunburn; and skin cancer.

• Ultraviolet radiation is a significant source of eye disease.

6

Guarding against sun damage and maintaining a young and healthy appearance requires nothing less than complete light protection for our skin.

Although skin can act as an effective barrier against many environmental insults, its ability to guard against harmful ultraviolet radiation is minimal and ineffective. We all need to be proactive and protect our skin year-round, even if we have a skin type that does not typically burn in the sun. Tanning may seem like an innocuous act, but what we think of as a “healthy tan” is actually a form of phototrauma; it harms the skin and can cause skin cancer. Moreover, tanning and burning, are not the only indicators of sun damage. Most of the harm done by UV exposure is not immediately visible; the injury is cumulative, adding up over an individual’s lifespan to degrade the architecture of the skin and create even more significant effects over time.

The skin’s poor ability to protect against the sun’s rays makes it necessary to shield our skin by using sunscreens that address the full spectrum of light and contain physical blocking ingredients that do not break down or cause harm in the presence of light. Doing so will help reduce chronic damage and carcinogenesis related to UVA and UVB radiation.

With some simple and consistent steps, sun damaged skin can be repaired, and other sun related issues can be minimized and possibly even reversed. A crucial step is an awareness that sun protection needs to be a daily, year-round practice. In particular, parents need to incorporate the use of sunscreen on a daily basis for their children. Frequent sun exposure and sunburn in childhood must be avoided, as they appear to set the stage for high rates of melanoma later in life. A comprehensive sun protection program includes broad-spectrum sunscreen as well as sun-protective clothing, sunglasses, staying out of the sun between 10 a.m. and 4 p.m. when UV rays are strongest, and avoiding the use of indoor tanning devices.

II. THE SUN’S EFFECT ON YOUR SKIN

II. The Sun’s Effect On Your Skin

7

The Facts of Light II: Sun and the Skin

• The skin is the largest organ in the human body.• Normal, healthy skin acts as a barrier and protects us from injury. It regulates our

temperature, receives sensory impulses and synthesizes Vitamin D.• Not all skin is the same. Different skin types respond differently to sunlight. Know your skin type and determine your vulnerability.• Sun damage to the skin is cumulative.• A suntan is a sign of skin damage.• Any level of tanning indicates photodamage that can lead to wrinkling, aging and skin

cancer.• Up to 90% of the visible changes commonly attributed to aging are caused by the sun.• Skin has a memory of all previous sun damage, resulting in greater susceptibility to skin

cancer.• More than 90% of non-melanoma skin cancers occur in fair skinned people who tend to

burn.• Dark skinned people, as well as fair skinned people, need to practice sun protection. While

the incidence of skin cancer is lower among dark skinned people, they are susceptible to damage from UV radiation, especially to damage of the eyes.

• Sun Protection needs to be a lifelong commitment. A popular misconception holds that 80% of a person’s lifetime sun exposure occurs before age 18; in reality the figure is closer to 23%.


Whendiscussingthesun’seffectonyourskin,therearethreemainaspectstoconsider:

1. CosmeticAppearance – Sun & light damage accounts for 90% of wrinkles, pigmentation changes and signs of aging, making it a primary determinant of our skin’s cosmetic appearance.

2. ImmuneResponse – Skin is our largest immune system response organ, and light affects the way it functions.

3. SkinCancerRisk – Sun exposure puts us at increased risk for skin cancer and its potential life threatening effects.

8

1. Cosmetic Appearance

Sundamageisresponsibleforupto90%ofthevisiblesignsofprematureagingonthehumanface,includingunwantedwrinkles.

We all know that the sun can alter our appearance by causing our skin to burn or tan, but we now know that much of what we once considered to be a natural aging process is actually the result of long-term exposure to sunlight. Sun exposure causes damage in the form of photoaging.

The term photoaging describes the microscopic alterations that result from continuous exposure to sunlight, especially UVA radiation. Cumulative exposure to the sun imparts damage to the epidermis (the outer layer) and the dermis (the deeper layer where the skin’s framework resides). The most striking features of photoaging are seen in the dermis, where virtually all of the skin’s structural components are altered. The elastic fibers are thickened and become more numerous. Collagen is damaged and degraded, and “reticulin” fibers appear throughout the dermis rather than outlining the specific dermal-epidermal junction.

In addition to wrinkling, visible blood vessels, skin roughness, pigmentation changes, and skin discoloration, the long-term consequences of photoaging include dramatic loss of skin elasticity and thinning of the skin. This is the result of ultraviolet radiation’s direct effect on the collagen matrix. The collagen matrix of the dermis is the ‘scaffolding’ that gives firmness and strength to the skin, but when exposed to ultraviolet radiation the collagen folds on itself, and as this happens, the skin thins, and wrinkles and furrows appear.

For a long time we believed that photoaged skin was irreversibly damaged, but it has now been shown to undergo significant repair when ultraviolet exposure is stopped. This important discovery proves that our skin does have the ability to repair itself from the sun’s harmful damaging effects and that sun protection plays an important role in that process. Proper use of sunscreen helps prevent photoaging while simultaneously allowing the skin to restore itself, or as clinical and research dermatologist Zoe Diana Draelos, M.D. stated it in the January/February 2007 issue of Aesthetic Dermatology News, “Sunscreens are the most effective anti-aging ingredient on the market today.”

Indoor Tanning

As we have become more aware of the link between sun exposure and skin damage, many people have resorted to indoor tanning. Indoor tanners think they are exercising a “safe option,” but tanning beds produce tans by emitting doses of UVA and UVB radiation. In the 1990s, high intensity devices that used UVB to produce deeper tans became available, as did high-pressure devices that emit UVA almost exclusively. Research into long-term impacts of tanning bed usage shows that there is nothing safe about this option. In 2009 the International Agency for Research on Cancer classified tanning devices as carcinogenic to humans. A study funded by the American Association for Cancer Research and published in 2010 concluded


9II. The Sun’s Effect On Your Skin

that users of indoor tanning devices were 1.74 times more likely to develop melanoma than individuals who have never tanned indoors, and for frequent users (defined as 50 hours, more than 100 sessions, or more than 10 years) the risk was 2.5 to 3 times greater than for non-users. Furthermore, the use of high speed / high intensity devices and high-pressure devices increased the likelihood of melanoma by 2.86 and 4.44 times respectively. The study suggests that no indoor tanning device can be considered “safe”.1

2. Immune Response

As the body’s largest organ, our skin is an integral part of our immune system; when skin is damaged our immune system is weakened. Skin is our primary line of defense and provides a barrier against many external threats, but radiation is not one of them. Ultraviolet radiation damages skin and compromises immune response, leaving us vulnerable to illness and infection.

We have known for some time that UVB radiation impacted immune responses including contact hypersensitivity (CHS) and delayed-type hypersensitivity response (DTH), and now more recent studies have demonstrated that UVA is also significantly involved in immunosuppression. Preventing UV induced immunosuppression requires us to protect ourselves from the entire UV spectrum.

3. A Forecasted Risk of Skin Cancer

1in5Americanswilldevelopskincancerintheirlifetimeasadirectresultofsunexposure.

Every year more than a million Americans are diagnosed with some form of skin cancer. Many of these skin cancers can be attributed to ultraviolet radiation and its harmful effects on the skin. Since most skin cancers are directly related to UVA and UVB radiation, it is important to note that just one serious sunburn in childhood can increase an individual’s chance of getting skin cancer by 50%. (For more detailed information on skin cancer, see Section V).

Facts of Light: Skin Repair

An effective sunscreen is the best way to maintain a youthful appearance, prevent immunosuppression, and avoid skin cancer. Though it was once believed that UVB radiation was the only wavelength harmful to the skin, evidence now suggests that UVA radiation is more significant when discussing long-term effects on the skin. For full protection against the sun and to preserve healthy skin, it is important to choose a sunscreen that protects against a broad range of the light spectrum, including both UVA and UVB radiation. Relying on SPF,

10 II. The Sun’s Effect On Your Skin

which measures protection against UVB and sunburn, is simply not sufficient when it comes to combating the full range of the sun’s effects on the skin.

To be effective, sunscreens must also be used consistently. UVA radiation is not filtered by window glass and is relatively unaffected by altitude or atmospheric conditions. Nearly twenty times more UVA reaches Earth’s atmosphere than UVB, and UVA penetrates deep into the dermis of the skin, where UVB does not reach. Unlike UVB radiation, UVA radiation is the same all day long and all year long. Because UVA radiation is so consistent throughout the day, it is important to use an effective sunscreen every day.

11

III. THE LIGHT SPECTRUM

Sunlight consists of fi ve forms of radiation ranging from wavelengths of 100 nanometers to beyond one million nm (infi nity). These radiation wavelengths trigger a variety of adverse photosensitive responses. Radiation emitted from artifi cial sources (mercury vapor lamps, welding arcs, and indoor tanning beds) also play a role in damaging skin.

Skin is our largest organ and an integral part of the immune system. In many cases, skin is the primary line of defense against external trauma. It can be an effective barrier against many environmental insults, but its natural capacity to protect against the sun’s radiation is limited, skin type dependent, and generally ineffective. Protecting skin from all injury, especially damage from sunlight, is critical to overall health. The damaging effects of ultraviolet radiation (UVR) from the sun are well documented and include everything from sunburn to photocarcinogenesis, immunosuppression, and photoaging.

Myth: Idon’tneedsunscreenonacloudydayFact: CloudsdonotblockUVrays.UVradiationlevelsarehighestundera cloudlesssky,butevenwithcloudcover,theycanbehigh.


ULTRAVIOLET VISIBLE LIGHT INFRARED

UVC UVB UVA

100 280 320 400 780

WAVELENGTH (NM)

12 III. The Light Spectrum

SUNLIGHT’S FIVE FORMS OF RADIATION

UltravioletC(UVC)–(100-280nm)UVC wavelengths are the shortest ultraviolet rays and are recognized as the most carcinogenic. UVC is severely photodamaging to the skin, resulting in skin burn with exposure. These wavelengths can very efficiently kill germs, giving rise to their common name, “germicidal waves.”

Fortunately, virtually all UVC generated by the sun is screened from reaching us by the protective ozone layer. Unfortunately, pollution damage to the ozone layer is undermining its protective ability, and UVC may become increasingly problematic for those living at high altitudes. If ozone depletion persists, the consequences will threaten life on a large-scale. Artificial sources such as some mercury arc-welding units and germicidal lamps also emit UVC.

UltravioletB(UVB)–(280-320nm)UVB is the intermediate wavelength of ultraviolet rays and causes the initial appearance of erythema, commonly called “sunburn”; usually perceived as redness. UVB primarily damages the epidermis (the outer most layer of the skin). The immediate result is skin redness and thickening of the skin’s outer stratum corneum, which is the body’s attempt to reduce UVB‘s impact on the epidermis. The superficial redness and painful irritation caused by UVB subsides after a relatively short period of time, but the underlying damage remains and accumulates, potentially resulting in basal cell and squamous cell cancers. Excessive exposure to UVB is the foremost promoter of premature aging of the skin. UVB also has significant immunosuppressive effects. Some indoor tanning devices also emit UVB.

In addition to staying out of the sun between 10 a.m. and 4 p.m. when UV rays are strongest, we can protect ourselves from UVB by applying sunscreen, wearing protective clothing and sunglasses, and avoiding tanning devices. The SPF rating assigned to a sun protection product is an indicator of its ability to protect against the UVB wavelength of light and is determined based on acute erythemal reaction, i.e. sunburn.

IMPORTANTNOTE:Choosing sun protection based solely on SPF is not enough. The common rule of thumb to “use SPF 30 or above” to protect your skin from sun damage is outdated, misleading and can be dangerous. SPF ratings pertain to UVB radiation only. UVB is not the only ultraviolet wavelength that damages the skin. SPF is not a sufficient or reliable indicator of the level of protection against any biological damage other than sunburn. As our understanding of light’s impact on skin has evolved, it has become clear that UVA adversely affects the deep dermis far more than the superficial “sunburn” caused by UVB rays, and mounting evidence suggests that UVA plays a relatively greater role in long-term photodamage.

UltravioletA(UVA)–(320-400nm)UVA are the longest of the ultraviolet wavelengths. While energy from the shorter UVB wavelength is absorbed in greater amounts in the epidermis and in keratinocyte DNA, energy from UVA penetrates more deeply into the dermis. Keratinocyte is the epidermal cell that

13

synthesizes keratin, known in its successive stages in the layers of the skin as basal cell, prickle cell, and granular cell.

Once thought of as essentially harmless, UVA causes the pigmentation changes associated with what we misguidedly refer to as a “healthy tan.” Scientific evidence now indicates that UVA is anything but harmless. In addition to skin darkening (tanning), UVA induces cutaneous photodamage, usually seen as dryness, uneven pigmentation, inflammation, fine wrinkles, and skin cancer. Even a low dose of UVA can cause photodamage leading to wrinkles and sagging skin. UVA adversely affects the deep dermis resulting in a loss of the elastic quality of its supportive collagen, causing premature aging. UVA exposure has been linked to the development of basal and squamous cell cancers, as well as precancerous lesions. Recent reports note that depletion of vitamin A in the skin caused by UVA exposure may contribute to both photoaging and cancers of the skin. Tissue damage from UVA rays is cumulative, and generally, the effects will not appear until after years of exposure2.

Several studies have demonstrated UVA’s involvement in tumor development and suppression of immune function. Skin’s upper layers present a weak resistance to UVA penetration and are not equipped to counteract photons that impact immune functions3. Epidermal pigment cells have been used in order to investigate the induction of DNA breaks due to UVA. What was determined is that with relatively low doses of UVA significant DNA breaks were found3.

UVA represents 90-95% of terrestrial UV radiation. It is estimated that 10 to 12 times more UVA than UVB reaches the earth’s surface at sea level. Unlike the shorter UVB wavelengths, UVA easily penetrates window glass and retains essentially the same energy level all day long, every day of the year, presenting the same damaging effects at 9 a.m. in December as it does at the 4 p.m. in July. Indoor tanning devices also emit UVA.

As with UVB, we can protect ourselves against UVA by staying out of the sun, applying sunscreen, wearing protective clothing and sunglasses, and avoiding indoor tanning devices. Products that address this wavelength specify “UVA Protection” or “Broad-Spectrum Protection” on the label. However, ”Broad-Spectrum Protection” is not total spectrum protection, and safely maintaining unaltered essential biological functions can only be achieved by well-balanced, photostable sunscreens that protect against the entire spectrum of UV radiation. Unfortunately, there is presently no standardized indicator, numerical or otherwise, to signify the level of protection against UVA, but sunscreens containing titanium dioxide and zinc oxide will protect against UVA radiation.


14

VisibleLight(400nm–780nm)As the name describes, visible light is the wavelengths that humans can see (violet, indigo, blue, green, yellow, orange, and red.). Nearly 50% of the sun’s radiation that reaches us at sea level is within the visible range. The energy level of visible light is lower than that of the ultraviolet wavelength, but it is a misconception to think of visible light as harmless to human skin. This lower energy has the ability to penetrate deeper into the skin than UVA and reach-down within the dermis to create adverse skin reactions. Scientific journals such as the “Journal of Investigative Dermatology”, “Cancer Research”, and the “British Journal of Dermatology” have published reports showing that visible light is capable of precipitating phototoxic reactions, promoting DNA cross-linking and enhancing tumor growth. Visible light’s significance as an active wavelength is evidenced by its current role in multiple Photo Dynamic Therapies (PDTs), some of which are used for the treatment of esophageal cancer, certain lung cancers and premalignant skin cancer.

Infrared-“IR”(greaterthan780nm-1,000,000nm)Infrared goes from above 780nm to infinity, but most of the energy is in the 780nm to about 1800nm range. It comprises more than 40% of sunrays that reach us at sea level. These wavelengths warm us when we stand in the sun (perceived as deeply penetrating heat) and are emitted by stoves, furnaces, light bulbs, heat lamps, ovens, and space heaters. A number of studies have implicated infrared waves as photodamaging. Chronic exposure to infrared light leads to mottled pigmentation, loss of elastin (elastosis) and the typical characteristics seen in photoaged skin (wrinkling, sagging, leathery-feel). Infrared has also been known to cause cancer, such as Kang Cancer in China, Kangri in Kashmir, Kairo in Japan, and Peat Fire Cancer in Ireland.


The Facts of Light III: The Truth About UVA

• UVA radiation is harmful to the skin and can cause skin cancer. Traditional long held thinking that UVB is the only type of radiation that causes harm to the skin is wrong.

• The longer UVA wavelengths penetrate the skin deeper than UVB radiation, reaching into the dermis, where they may damage underlying structures such as blood vessels.

• UVA radiation promotes the photoaging process initiated by UVB. • UVA may initiate photodermatosis reactions and photosensitivity responses to drugs and

chemicals.• SPF is not an indicator of a sunscreen’s ability to protect against UVA radiation; SPF

addresses UVB radiation only.

15

A Sun Protection Primer

• Daily sun protection will help prevent skin damage, wrinkles and reduce the risk of cancer.• When choosing a sunscreen opt for one that is rated SPF 30 or higher and says “UVA

Protection” or “Broad-Spectrum Protection” on the label; and apply to all exposed skin, including the lips.

• Use sunscreen every day, even when it’s cloudy.• Water resistant sunscreen should be used when you will be exposed to water, either through

swimming or sweating.• Reapply sunscreens frequently. At least every 2-4 hours; more often if it is sunny or when

you are perspiring heavily.• Wear a broad-brimmed hat, sunglasses and protective, tight woven clothing.• Seek shade wherever possible.• Plan outdoor activities early or late in the day to avoid peak sunlight between 10 a.m. and 4

p.m.• Sunscreens work by absorbing, reflecting or scattering the sun’s rays on the skin. They are

available in many forms including ointments, creams, gels, lotions and sprays. • Sunscreens are categorized by SPF numbers. The higher the SPF, the greater the

protection from sunburn, caused mostly by UVB rays. • Some sunscreens called “broad-spectrum” reflect both UVA and UVB rays. • “Broad-spectrum” is not total spectrum protection.• Sunscreens containing titanium dioxide and zinc oxide will protect against UVA radiation.• Consider specific products for specific areas. (e.g.: The face and chest typically receive

significantly more exposure than do the back and abdomen.)• Sunscreens containing chemical filters should be applied about 1/2 hour before going

outdoors.


16

Choosing the Right Sunglasses

• UV radiation is linked to cataracts and macular degeneration.• Choosing the right sunglasses will prevent long-term exposure to the sun’s ultraviolet rays

and help prevent eye damage.

Sunglassesshould:• Provide maximum protection from ultraviolet (UV) rays• Block at least 98 percent of the sun’s UV rays• Carry an American National Standards Institute (ANSI) label listing how much UV light

they block. Important Note: Sunglasses claiming to provide maximal UV protection do not necessarily meet ANSI standards – look for the ANSI label!

• Fit close to your face. Wraparound sunglasses give more complete protection from all angles of light.

Polarizedlenses• Provide extra comfort for your eyes and block glare from such things as pavement,

sand, water, snow or the hood of your car.• Most provide protection from UV rays.


17

IV. SPF IS NOT ENOUGH


Myth: UsingasunscreenwithanSPFof30isenoughsunprotection.Fact: TheSPFratingdoesnotaddressUVAradiation.

On the face of it, Sun Protection Factor, commonly known as SPF, seems simple. Every sunscreen is assigned an SPF number. This number is the factor by which the amount of time it takes for sunburn to occur is increased when sunscreen is used versus when skin is left unprotected. It is an important measure, but it’s not all there is to know about sunscreen, and this is a case where what you don’t know can hurt you.

While SPF is a useful number, it is neither an absolute value nor is it simple. It is determined under laboratory conditions that may or may not mimic the way individuals use sunscreen in the real world (individuals are unlikely to apply sunscreen in the amount used for laboratory testing). To further complicate an understanding of this number, when efficacy is considered relative to the percentage of energy that is reflected or absorbed, SPF does not provide a linear scale. And, perhaps most importantly, SPF is an indicator of only one type of protection. Current SPF rating does not adequately measure protection from all the damaging radiation effects of light.

Sunburn At a Glance

• Ultraviolet B rays have long been known to harm the skin.• Sunburn is inflammation of the skin due to overexposure to ultraviolet (UV) rays.• Sunburn damages the skin; the damage is cumulative and can be permanent.• Sunburn can be serious and require professional medical attention.• Victims of severe sunburn should avoid bathing in cold water.• Many prescription and non-prescription drugs and products increase the skin’s sensitivity to

sunlight.• The UV from “sun tanning” lamps is as damaging to skin as sun exposure.• The main environmental cause of skin cancer is the sun.

The Facts of Light IV: The Truth About SPF

• SPF merely addresses the UVB wavelength not UVA, UVC, visible, or infrared light.• The accuracy of the SPF number is questionable as testing is done with more product

than is realistically used when sunscreen is applied. Consider the reality that the true SPF number is about 1/2 or 1/3 of the stated number.

• Using a higher SPF sunscreen can help overcome “user-errors”, e.g. sporadic use of product, not reapplying frequent enough or in an adequate amount.

• When utilizing titanium dioxide and zinc oxide, the higher the SPF the more UVA coverage.• The UVA ray is more difficult to study on human subjects due to the length of time it takes for

damage to appear. Aging skin or mutating skin cells are cumulative and can take decades to manifest fully.

18

While regulatory guidelines do exist, they are problematic. In the United States, the testing guidelines established by the Food and Drug Administration only account for UVB protection. Unlike other countries, the U.S. FDA has not established guidelines to test a product’s protective ability relative to UVA, which is known to cause cancer and other skin damage. Whether done in the U.S. or in another country, testing to determine SPF is agreed upon by a uniform central body, but actual testing is decentralized. This means there may be variations in how guidelines are interpreted and they may be applied inconsistently. As a case in point, recent reports issued by a consumer watchdog magazine published in the UK, have raised serious questions about the accuracy of SPF ratings listed on European sunscreen labels. Using the test endorsed by the European Union (EU) recommendations on sunscreen labelling, the magazine annually tests the SPF of sunscreens to strict international standards and compares the resulting information to product label claims. For these tests, sunscreen is applied to a small test area on the backs of 12 volunteers who are exposed to UVB rays from a special lamp that stimulates sunlight and records when the skin turns red. In both 2008 and 2009, the magazine found that although a few sunscreens exceeded the SPF rating on their labels, many offered a lower SPF than the labelling indicated. In 2008, four sunscreens labelled as SPF 15 were found to only provide an SPF of 9.3 to 12.1.

In relative scales SPF means the percentage of sunlight that is absorbed or reflected due to the level of the SPF. For example, an SPF with a value of 100 would reflect or absorb 99% of UV rays, whereas an SPF with a value of 10 reflects or absorbs 90%. The scale is not a linear scale; rather it is derived by the way SPF is calculated.

Finally, the technical explanation of the benefits of 30+ SPF is complicated. For instance, an SPF 15 product blocks 93% of incidental UVB light, while SPF 34 blocks 97%, a seemingly insignificant difference. Nevertheless, a dermatologist in Philadelphia, Pennsylvania completed an instructive model using human skin volunteers showing that skin protected with an SPF 30 sunscreen had 2.5 times fewer sunburn damaged cells than skin protected with an SPF 15 sunscreen when both areas were exposed to enough simulated solar radiation to cause the beginning of redness4. Thus, there is at least a two-fold difference in the protection offered by the higher SPF.


19

SUN PROTECTION FACTOR EFFICACY

SPFValue %EnergyAbsorbed/Reflected

%EnergyTransmitted(1/SPFValue)

2 50.0% 50.0%4 75.0% 25.0%6 83.3% 16.7%8 87.5% 12.5%

10 90.0% 10.0%15 93.3% 6.7%25 96.0% 4.0%30 96.8% 3.3%35 97.1% 2.8%40 97.5% 2.5%50 98.0% 2.0%60 98.4% 1.6%

100 99.0% 1.0%

Full Spectrum Sun Protection: What the Number Doesn’t Tell You

Myth: Whenaproduct’slabelsays“UVB/UVA,”itoffersfullspectrumsun protection.Truth: TheFDAcurrentlyhasnoratingsystemforUVA.

SPF, the only approved FDA standard for rating sunscreens, tells only about a product’s ability to protect against UVB’s burning rays. While most currently available sunscreen products assess their protection based on SPF measurements, many also feature a “broad-spectrum” claim on their label. Consumers may infer that the SPF of these ‘broad-spectrum” products protects against both UVB and UVA. SPF refers only to the sunscreen’s ability to block or absorb UVB; the level of UVA protection is not related to SPF ratings. In fact, UVAprotectioncanwidelyvarybetweenproductswiththesameSPF.

There is no currently approved standard for rating the quality of a sunscreen’s ability to protect against UVA. The lack of a UVA rating system is unfortunate because UVA penetrates deeper and is more often associated with skin changes such as wrinkling, pigmentation, and long-term


20 IV. SPF Is Not Enough

damage. Both UVB and UVA are recognized to cause skin cancer. In the absence of accurate information, we may easily believe we are safer in the sun than we really are. Fortunately, steps are being taken to address this information deficiency. In the meantime, it is good to keep in mind that in the case of products utilizing titanium dioxide and zinc oxide, a higher SPF actually does provide more UVA coverage.

Measuring UVA Protection

The difficultly in devising a rating system for UVA protection arises from the lag in time that exists between exposure and the appearance of damage. Unlike UVB, which announces damage fairly immediately in the form of sunburn, skin changes induced by UVA, e.g. aging and cell mutation, can take decades to manifest.

Nevertheless, the importance of devising such a system is supported by studies such as Protection of Skin Biological Targets by Different Types of Sunscreens, conducted by A. Fourtanier, F. Bernerd, C. Bouillon, L. Marrot, D. Moyal, S. Seite´ L’Ore´al Recherche, and Clichy Cedex, which concludes that in vitro and in vivo tests provide a body of evidence that adequate protection of the skin against UV induced damage requires photostable broad-spectrum sunscreens with a proper level of UVA protection.

In 2008, The American Academy of Dermatology (AAD) convened a consensus conference with the U.S. Food and Drug Administration (FDA). The goal was to provide recommendations regarding assessment methods to serve as the basis for labeling sunscreen products relative to UVA protection. The Academy recommended two measures: in vitro (Lab) testing, which evaluates the breadth of the protection across the UVA spectrum, and an in vivo (Human) test that measures the height of the protection.

In vivo testing employs two methods: Protection Factor in UVA (PFA) method and the Persistent Pigment-Darkening (PPD) method. These two methodologies have been shown to give virtually identical results and have been used interchangeably, but there are differences that may make the PFA test more suitable for widespread application. The PPD test, which only measures pigment darkening (tanning), is limited to use with darker skin types. In contrast, the PFA test can be used on fair skin as well as darker skin types, and its end points can be either erythema or pigment darkening. PFA values have also been shown to be reproducible between different laboratories, furthering supporting its value as a viable method for testing UVA protection.

As with SPF testing, the PFA value is a factor representing the ratio between how much sun the skin can tolerate with sunscreen protection relative to what can be tolerated without sunscreen protection. Clinical PFA testing mimics the traditional SPF test, but uses a light source that emits only UVA radiation. The protection factor is determined by administering a series of UVA exposures to sunscreen protected skin and adjacent unprotected sites. Intensity is increased by a standard increment with each exposure.

21IV. SPF Is Not Enough

After 24 hours, exposed sites are examined, compared and rated for erythema or pigment responses. The percentage of UVA blocked by a particular sunscreen can then be calculated based on the PFA.

It is hoped that when approved, the impending U.S. Food and Drug Administration’s updated sunscreen monograph will incorporate new testing and labeling requirements for products that protect against UVA rays. Proposed amendments include requiring the primary labeling panel to include ratings for both UVA and UVB protection; revising SPF to mean “sunburn protection factor” and labeling products based on providing low (2-14 SPF), medium (15-29 SPF), high (30-50 SPF) or highest (50+ SPF) results; and including a four-star UVA rating system. Products that do not provide any UVA protection would be required to state “No UVA Protection” near the SPF value. These changes will offer consumers a more complete picture and allow them to more easily make wise sun protection choices. In the meantime, they rely on doctors, physician assistants, nurses and aestheticians for sound sun care guidance.

Myth: Applyingsunscreeneverymorningaffordsamplesunprotection.Fact: Frequentandadequatereapplicationofafullspectrumsunscreenis essentialduetomoisturelossandrubbing.

22

V. SKIN CANCER

V. Skin Cancer

ThemostcommonmalignancyintheUnitedStatesispreventablewitheffectivephotoprotectivemeasuressuchastheuseoffullspectrumsunscreen.

Skin cancer is the most common form of cancer in the United States. Each year in excess of one million Americans are diagnosed with some form of skin cancer, and many more are diagnosed with precancerous conditions. Ninety percent of these cancers are caused by exposure to the sun’s damaging ultraviolet rays, which means the majority of them are also preventable.

Despite the alarming statistics many people continue to believe a suntan is healthy and think of sunscreen as an occasional, summer-only accessory. These attitudes are particularly prevalent in the teen and young adult population.

Skin Cancer Facts:

• The American Cancer Society estimates that more new cases of non-melanoma skin cancer are discovered each year than all other forms of cancer combined.

• One in five Americans will develop skin cancer in the course of a lifetime.• Melanoma is the most common cancer for women aged 25-29 and the second most

common cancer for women aged 30-34.• The death rate for men over 50 with melanoma has risen 50% in the past 15 years.• Basal cell carcinoma (BCC) is the most common form of skin cancer; about one million of

the cases diagnosed annually are basal cell carcinomas. • Although rarely fatal, basal cell carcinomas can be highly disfiguring. • Squamous cell carcinoma (SCC) is the second most common form of skin cancer. More

than 250,000 cases are diagnosed each year, resulting in approximately 2,500 deaths. • Between 40 and 50 percent of Americans who live to age 65 will develop either basal cell

carcinoma and squamous cell carcinoma skin cancer at least once.• In 2004, the total direct cost associated with the treatment for non-melanoma skin cancers

was more than $1 billion. • About 90 percent of non-melanoma skin cancers are associated with exposure to ultraviolet

(UV) radiation from the sun. • Every 9.39 minutes someone dies of Melanoma.

Several factors appear to be responsible for the rapid growth of the number of skin cancer cases. Pollution has steadily eroded the earth’s ozone layer and left us less protected by the atmosphere than was the case for previous generations. Today there are also over 400 prescription medications in common use that increase a patient’s sensitivity to sun exposure and heighten susceptibility to sun damage. And, perhaps most importantly, exposure to the UVA wavelength has increased. Previously thought of as harmless, UVA is now known to contribute significantly to skin damage, skin cancer, DNA damage and immune system suppression. UVA

23

rays penetrate the skin deeper than UVB rays, and unlike UVB, which causes initial redness and burning, UVA causes damage that is not immediately evident. UVA rays remain constant throughout each day and throughout the year, providing a continuous and on-going threat.

Without treatment, skin cancer can metastasize to other areas of the body and become deadly. Fortunately, the majority of skin cancers are visible and can be caught early, often in the precancerous stage. With early detection, most skin cancer is treatable without long-term complications. Basal cell carcinomas and squamous cell carcinomas can be treated using a variety of methods including scraping and freezing for early skin cancers and surgical removal for more advanced cancers. Melanoma is treated by surgically removing the growth. Mohs micrographic surgery is a special surgical procedure used to ensure the complete removal of a skin cancer while sparing normal skin. Although the surgical removal of skin cancers inevitably leaves scars, appearance can usually be restored to a high degree after skin surgery.

Even with successful treatment, multiple skin cancers can be a real burden for patients. Multiple surgical procedures may be required, and the process of removing lesions may produce scars that can alter appearance. Having skin cancer is not an insignificant medical event; prevention is the best approach of treatment.

1. Precancerous Skin Conditions:

ActinicKeratosis (see figure 1)Actinic Keratosis (AK) are the most common type of precancerous skin lesions. One of every ten visits to a dermatology office is prompted by AK’s, and approximately $1.04 billion is spent on AK treatment each year.

Actinic Keratosis usually appears as small pink or red bumps with rough, crusty or scaly surfaces. They are often more easily felt than seen. If AK’s are left untreated there is a good chance it will develop into squamous cell carcinoma (SCC). In fact, an estimated 40% to 60% of SCC originates as untreated AK lesions.

The likelihood of developing Actinic Keratosis is directly related to lifetime sun exposure –the more time spent in the sun, the greater the chance that AK will develop. In light of this, it is not surprising that AK is most common in older individuals and outdoor workers or that it is most likely to appear on areas of the body that are commonly exposed to sunlight such as the face, lips, ears, scalp, shoulders, forearms, and back. AK’s are also most common among people with fair skin types.

NumerousrandomizedstudieshavedemonstratedthatpropersunscreenusagedecreasestheincidenceandprevalenceofActinicKeratosis,reducesthemultiplicityoflesions,andincreasestherateofregression5.

V. Skin Cancer

24

Actinic Keratosis TreatmentAK can be addressed using a variety of surgical and non-surgical treatments.Surgical options are typically used when treating localized disease, focusing on the removal of a limited number of distinct lesions. While efficacious for eliminating damaged tissue, most surgical options result in epidermal changes or scarring. Non-surgical options are generally reserved for patients with multiple lesions because they enable targeting the entire field. A microscopic diagnosis as confirmed by a probe biopsy is often recommended prior to non-surgical AK therapy.

Surgical Options

Cryosurgery: The most common treatment for Actinic Keratosis is cryosurgery, which involves freezing lesions with liquid nitrogen. Cryosurgery does not require anesthesia or result in bleeding, although it may cause temporary redness and swelling. Longer freeze time can cause permanent hypopigmentation at the application site6.

CurettageandShaveExcision: This method is effective for patients with a limited number of lesions. Atypical tissue is “shaved off” using a small blade or curette. Removed tissue is sent to biopsy to check for malignancy. Minor bleeding is common and typically controlled by cauterizing the wound. Curettage can also be combined with cryosurgery6.

LaserSurgery:Carbon dioxide or erbium yttriumaluminum garnet lasers can be used to excise damaged tissue without causing bleeding or injuring the deeper layers of the skin. The precision of laser surgery makes it particularly appropriate for lesions located in small or narrow areas, such as the lips or eyes. Local anesthesia is often required. Patients may have localized pigment loss (some studies report nearly 50% of treated patients experience hypopigmentation). This technique can be used as a secondary treatment when other methods have produced less than optimal results6.

Non-Surgical Options

5-Fluorouracil: 5-Fluorouracil is used to treat multiple lesions on the face and scalp. The cream is typically applied to each lesion once daily over a 1 to 4 week time period. Pooled data from 2 clinical trials found that just over 50% of patients achieved total clearance after 4 weeks of treatment with 5-flourouracil. The most commonly reported adverse effect was facial irritation (related to dose-response and dose-duration). Other adverse effects include eye irritation, headache, common cold, sinusitis, allergy, and skin irritation6.

Diclofenac: This common protocol involves topical application of 3% diclofenac in 2.5% hyaluronan gel. Gel is administered to each lesion twice daily for 60 to 90 days. A study of 195 patients with at least 5 AKs demonstrated that a greater proportion of patients

V. Skin Cancer

25V. Skin Cancer

who received diclofenac twice daily for 60 days experienced 100% lesion clearance than those in the placebo group. The most commonly reported adverse effects are pruritus, rash, dry skin, and application-site reactions6.

PhotodynanicTherapy(PDT):Relying on differences in tissue sensitivity to wavelength absorption, PDT uses various light sources along the porphyrin absorption spectrum (eg, blue, green, red light) to photosensitizing agents such as aminolevulinic acid (ALA). What results are oxygen species that promote tumor destruction. To assess the effectiveness of PDT for AK treatment, one study evaluated patients with at least four nonhypertrophic facial AKs and mild to moderate diffuse facial photodamage. Participants were given either 40% urea cream or a placebo, which they applied to one half of the treatment area for seven days. PDT-ALA was then administered to the entire treatment area for 1, 2, or 3 hours. Clearance rates for active treatment and placebo cohorts were the same, but both groups reported significant reduction in the number of lesions at one and five months. Adverse effects include mild-to-moderate discomfort at the time of treatment and moderate phototoxic effects for one week following treatment6.

Imiquimod: Imiquimod cream is applied topically. Two studies of patients who applied imiquimod 5% cream twice weekly for 16 weeks demonstrated a complete clearance rate of 45.1% and partial clearance rate of 59.1% when patients were evaluated 8 weeks post-treatment. Adverse effects include application-site and local skin reactions and severe erythema6.

Retinoids:Retinaldehyde, a natural derivative of vitamin A, has effects similar to retinoic acid. It is known to counteract ultraviolet induced vitamin A deficiency of the epidermis and may have an antioxidant effect that can decrease the number of sunburned cells. Retinoid treatment of AK’s are currently considered an off-label use. Only limited evidence exists to support use of topical retinoids for AK treatment, although one study demonstrated an 84% reduction in lesions after 4 months of treatment with tretinate. Systemic administration of retinoids is sometimes used to treat very high-risk patients (such as organ transplant recipients) who are at increased risk of progression to squamous cell carcinoma. Retinoid therapy is associated with considerable morbidity, including severe erythema, erosions, pruritus, and pain, possibly limiting its use in clinical practice6.

Customizing Actinic Keratosis TherapyThe American Academy of Dermatology’s most recent AK treatment guidelines were published in 1995, therefore, they do not address several therapies (such as imiquimod, diclofenac, and PDT) that have since been approved and become standard treatment options. Despite this, several major recommendations maintain their relevancy. These include the potential for combining surgical and nonsurgical therapies; the importance of long-term follow-up; emphasis of preventive measures (sun avoidance, protective clothing, sunscreen), early detection by self-examination, and most notably, the importance of customizing therapy.

26

Customized AK therapy considers a number of factors including patient’s overall health and ability to tolerate the treatment; lesion size, location, and duration; lesion growth pattern; previous dermatologic treatments; efficacy; adverse effects; ease of use, and physician and patient preferences. Risk for lesion recurrence is also an important consideration. According to a 2006 analysis of literature conducted by the Guideline Subcommittee of the European Dermatology Forum, reports of one-year recurrence rates varied widely based on treatment. As an example, recurrence rates were between 1% and 12% for cryosurgery, 10% for imiquimod, and up to 55% for 5-fluorouracil6.

Because AK generally affects individuals who have had excessive sun exposure and, therefore, a propensity for developing malignancy, field therapy may be warranted to treat visible and non-visible lesions in combination with lesion-directed therapy to ensure optimal outcomes.

On-going research into AK therapies focuses on confirming the relative efficacy and safety of various treatments, evaluating alternative treatment regimens, and optimizing delivery of currently approved modalities. New information offers the potential for improving outcomes and creating additional avenues for customizing AK treatment.

V. Skin Cancer

2. Skin Cancer:

BasalCellCarcinoma(BCC) (see figure 2)Basal cell carcinoma arises in the basal cells, which line the deepest layer of the epidermis, and usually appears as a pearly papule or as a small pink bump or patch. BCCs grow slowly and rarely spread to other parts of the body, however, if left untreated, they will begin to ulcerate, bleed or crust repeatedly and can cause severe disfigurment.

Figure 1: Actinic Keratosis Figure 2: Basal Cell Carcinoma (BCC)

Figure 3: Squamous Cell Carcinoma (SCC) Figure 4: Malignant Melanoma

27V. Skin Cancer

Most BCCs are linked to UV exposure, but in some cases contact with arsenic, exposure to radiation, open sores that resist healing, chronic inflammatory skin conditions, and complications of burns, scars, infections, vaccinations, or even tattoos are contributing factors.

Almost all BCCs occur on parts of the body that receive the most sun exposure: the face, ears, neck, scalp, shoulders, and back. Tumors can develop anywhere on the body, but they rarely appear in areas that are routinely protected from sunlight.

BCC is the most common form of cancer of any type in the United States. Approximately one million people are affected each year; that’s four times the number affected by squamous cell carcinoma. Anyone with a history of sun exposure can develop BCC, but the highest risk is among people who have fair skin, blond or red hair, and blue, green, or grey eyes. Outdoor workers and people who spend their leisure time in the sun are also particularly susceptible. Traditionally, older people have comprised the vast majority of BCC patients, and men with the disease have outnumbered women, but that has changed during the past several decades. As the number of new cases has risen sharply, the number of women being treated for this skin cancer and the number of people in their twenties and thirties has significantly increased,

• NodularBCC is the most common type of BCC. Telangiectasia may become evident as the lesions expand.

• PigmentedBCC, commonly seen as a black/blue papule or nodule, can sometimes resemble melanoma, but can be distinguished by its speckled or waxy appearance.

• SclerosingBCC is sometimes also known as scaring BCC. It is usually the most difficult type of BCC to treat because it often broadens past its assessed border. Sclerosing BCC is characterized by its white, plaque-like appearance that often resembles a scar.

• SuperficialBCC is red pearly papule or plaque that is occasionally scaly.

SquamousCellCarcinoma(SCC)(see figure 3)Squamous cell carcinoma arises in the squamous cells, which make up most of the skin’s epidermis. In appearance, SCCs are similar to basal cell carcinomas, but they are more prominently raised from the surface of the skin and are rougher and more scaly. SCC is easily cured if treated early, but when allowed to advance, tumors can penetrate deeply into the skin and spread to the lymph nodes, requiring more extensive treatment. If treatment is not successful death is possible. SCCs have a low probability of metastasizing, but it is far more likely to occur with lesions on the lower lip or ear. As with basal cell carcinoma, most SCC cases are caused by chronic exposure to sunlight. Other contributing sources are frequent use of tanning beds (users are 2.5 times more likely to develop SCC1), skin injuries (burns, scars, ulcers, long-standing sores), chronic infections and skin inflammation, exposure to X-rays, and contact with certain chemicals (such as arsenic and petroleum by-products). HIV, other immune deficiency diseases, chemotherapy, anti-rejection drugs, and excessive sun exposure all weaken the immune system and undermine the body’s ability fight off disease, thus increasing the risk of squamous cell carcinoma and other skin

28 V. Skin Cancer

cancers. Solid organ transplant recipients, who rely on immunosuppressive medications to prevent their bodies from rejecting donated organs, are 65 times more likely to develop skin cancer than the general public7. On rare occasions, SCCs spontaneously appear on apparently normal, healthy skin. Some researchers believe the tendency to develop these cancers can be inherited.

SCCs can occur anywhere on the body including the mucous membranes and genitals, but they are most common in areas that are frequently exposed to the sun: the rim of the ear, the lower lip, face, bald scalp, neck, backs of hands, arms and legs. Skin in the effected area may display the tell tale signs of sun damage: wrinkling, changes in pigmentation, and loss of elasticity.

SCC is the second most common type of skin cancer. More than 250,000 new cases of squamous cell carcinoma (SCC) are diagnosed every year. It is the most common skin cancer in organ transplant patients (seventy percent of fair skinned transplant recipients with develop skin cancer within 20 years of their transplant7). The risk of developing SCC is higher for anyone with a history of substantial sun exposure, people who have fair skin, anyone who has had a basal cell carcinoma, and anyone with UV-sensitive condition such as xeroderma pigmentosum. SCC is at least twice as frequent in men than in women. They rarely appear before age 50 and are most often seen after age 70.

MalignantMelanoma(seefigure4)Malignant melanoma typically appears as an irregular brown, black and/or red spot or a changing mole. It is curable if caught early, but in about 15% of patients, melanoma spreads to other parts of the body and can result in death. It is characterized by aggressive local growth, with the exception of nodule melanoma.

Researchers have established a direct cause and effect relationship between Ultraviolet light and melanoma. A pooled analysis of 15 case studies (comprised of 5,700 melanoma cases and 7,216 controls) investigating the relationship between sun exposure and melanoma risk at different latitudes concluded that melanoma risk at different body sites is associated with different amounts and patterns of sun exposure. Specifically, it found that recreational sun exposure and sunburn are strong predictors of melanoma at all latitudes, whereas measures of occupational and total sun exposure appear to predict melanoma predominately at low latitudes8. ArecentUniversityofMinnesotastudyhasalsoestablisheddoseresponsecorrelationbetweentheuseofindoortanningdevicesandmelanomarisk.

Melanoma accounts for about 10% of dermatological malignancies but is responsible for 75% of skin cancer deaths. Melanoma accounted for an estimated 68,720 cases of skin cancer and 8,650 of the approximately 11,600 deaths due to skin cancer in 20099. It is the most common type of cancer for Caucasians ages 25-29 and the second most common cancer for women ages 30-34. It is more common in males than in females. A 50% increase in the death rates of men over the age of 50 has been reported during the past 15 years9.

29

• Superficialspreadingmelanoma accounts for 70% of melanoma cases. It usually occurs as either a red, black, white, blue, or purple papule or nodule. This specific type of melanoma can occur anywhere on the body, but is most commonly found on the back or legs.

• Nodularmelanoma accounts for 15% of melanoma cases. It is often a blue or black nodule. It can also appear as a flesh-colored tumor. Unlike other types of melanoma, it lacks a horizontal growth phase. In the absence of a horizontal growth phase, it tends to be presented on the skin at an advanced stage.

• Acrallentiginousmelanoma accounts for 10% of all melanoma cases. It is found on the hairless skin of the palms, fingers, toes, nail beds, and soles of the feet. People of African, Asian, or Hispanic descent, have a higher incidence of this type of melanoma relative to other types of melanoma.

• Lentigomalignamelanoma is usually in the form of a black or brown macule on already sun damaged skin. It is characterized by a prolonged horizontal growth phase that often lasts years before it attacks the dermis.

For early detection, look for skin changes as well as new growths and remember the ABCDEF’s of melanoma:

• Asymmetryoflesion:Are both sides of the lesion different?• Borderirregularity:Are the edges notched as opposed to smooth?• Colorvariation:Is the lesion a mixture of black, blue, red, and white?• Diameter:Is the diameter greater than six millimeters?• Evolution: Is the lesion growing in width or height?• Feeling:Has the sensation around a mole or spot changed?

Clark ClassificationThe Clark model of the progression of melanoma emphasizes the stepwise transformation of melanocytes to melanoma. The model depicts the proliferation of melanocytes in the process of forming nevi and the subsequent development of dysplasia, hyperplasia, invasion, and metastasis. Numerous molecular events have been associated with the development of melanoma.

3. Prevention:

According to Robert Friedman, M.D, Clinical Associate Professor in the Oncology Division of the Department of Dermatology at New York University School of Medicine “Sun protection in the form of broad-spectrum sunscreens, wearing protective clothes during sun exposure, and time of day during which exposure takes place all factor into helping protect against melanoma and all skin cancers.”

V. Skin Cancer

30 V. Skin Cancer

Dr. Friedman and most other doctors agree that minimizing sun exposure is the best way to prevent skin damage and many types of skin cancer. You can take action to reduce your risk for developing skin cancer by:

• Avoidingmiddayexposurewhen the sun is most intense. • Usingsunscreeneveryday,allyearlong.Choose a full spectrum sunscreen with an

SPF of 30 or above. Reapply frequently. • Findingshade. Look for shady area under an umbrella or tarp.• Coveringup.Wear sun protective clothing to shield your skin from the sun.• Wearingahat.Pick one with a large brim to protect the ears and neck.• Wearingsunglasses. Use sun protective or UV filtering sunglasses to protect your eyes

from harmful UV rays.• Protectingyourchildren. Babies under 6 months of age should be completely shielded

from direct sun exposure. Apply sunscreen to infants over six months of age, and teach older children to make applying sunscreen a regular habit before they go out to play.

• Abstainfromusingtanningbedsorotherartificialsunlightsources. The International Agency for Research on Cancer classified tanning devices as carcinogenic to humans10.

31

VI. VITAMIN D

Sun presents a paradox when it comes to health. Unprotected sun exposure damages skin, suppresses the immune system, and increases skin cancer risk. Exposing unprotected skin to the sun helps to naturally manufacture the body’s daily requirement of vitamin D, an important vitamin that plays a significant role in bone health and bone strength. Recent research suggests that vitamin D may also reduce the risk for numerous diseases and lower overall mortality rates. Vitamin D deficiency is common in the United States, and some people use that fact to justify ignoring sun protection16. Are they right?

According to David M. Pariser, MD, FAAD, and former president of the American Academy of Dermatology (AAD), “Concern about vitamin D should not lead people to forego sun protection, but rather prompt a conversation with their physician about how to ensure adequate and safe vitamin D intake while guarding against skin cancer.” While acknowledging the importance of maintaining adequate vitamin D levels, the AAD recommends procuring it through a healthy diet that incorporates foods naturally rich in vitamin D, vitamin D fortified foods and beverages, and vitamin D supplements11.

Moreover, relying on the sun for vitamin D is not as straightforward as it may seem. While it is true that direct sunlight triggers vitamin D production, various factors impact the body’s ability to perform this process. The season, geographical latitude, time of day, cloud cover, duration of exposure and the amount of skin exposed all affect UV ray exposure and thus vitamin D synthesis in the skin.

VI. Vitamin D

Sunlight has its Benefits…

• Sunlight is a primary source for vitamin D, which helps keep our bones strong. • The current recommended daily intake of vitamin D is 200 IU from birth to age 50, 400 IU

between 51 and 70 years, and 600 IU after age 71.• Recent studies suggest that 1,000 IU a day may reduce the incidence of certain cancers—

such as those of the ovary, breast and colon—by as much as 50%. That is because vitamin D strengthens the immune system and controls cell growth.

• Vitamin D requirements may also be satisfied by diet (a serving of oily fish contains between 250 and 360 IU, and one tablespoon of cod liver oil has 1,360 IU) and/or supplements (alone or combined with calcium).

I. What is Vitamin D? Why is it Important?

Vitamin D is the only vitamin our own bodies can manufacture. It is a fat-soluble vitamin that is the precursor to a potent secosteroid hormone that is used by a variety of cells in the human body. Nevertheless, most health care providers aren't fully aware of the importance of vitamin D levels, the prevalence of deficiency and the health benefits of achieving a therapeutic level of vitamin D.

32 VI. Vitamin D

Adequate levels of vitamin D have long been associated with developing and maintaining strong, healthy bones, but the latest research suggests that vitamin D may play a more important role in health than had been suspected. Research to investigate vitamin D as a potential prevention and treatment tool for heart disease, diabetes, depression, hypertension, multiple sclerosis, autoimmune illness, and osteoporosis is under way. Vitamin D has been shown to impact:

• BoneHealth– Vitamin D increases our ability to absorb calcium, which is essential for strong bones and teeth. A vitamin D deficiency can result in weakened skeletal development in childhood and a weaker skeletal system in adulthood. Osteoporosis can be greatly reduced with adequate levels of vitamin D, and many studies have proven that vitamin D is effective in preventing bone fractures12.

• MuscleStrength– Vitamin D is vital for muscle strength. Inadequate levels have been associated with muscle weakness and aches; increased loss of muscle mass with aging; and a higher risk of falls and fractures, especially in older women13.

• HeartHealth– Although study results have been mixed, some evidence suggests that vitamin D may help reduce hyerptension and lower blood levels of C-reactive protein, which has been associated with heart disease13.

• Immunesystem – Autoimmune diseases can be greatly reduced with adequate levels of vitamin D. In both animal and human studies, giving subjects adequate vitamin D helped protect against such diseases as multiple sclerosis, psoriasis, and inflammatory bowel disease – diseases in which the immune system reacts against body tissue13. A 2006 report published in Journal of the American Medical Association showed a potential link between vitamin D deficiency and the onset of multiple sclerosis14. Vitamin D can also greatly reduce the risk of rheumatoid arthritis. Vitamin D appears to help make immune system cells less likely to react against the body’s own tissues; it may be a necessary ingredient in activating an immune response mechanism that triggers the body to recognize self from non-self.

• Cancer– An increasing body of research supports the idea that vitamin D may provide significant protective effects against cancer. A review of dozens of articles published between January 1966 and December 2004 revealed a positive relationship between cancer risk and blood serum vitamin D levels or oral intake of vitamin D. This research identified a definite link between vitamin D deficiency and higher rates of colon, breast, ovarian and prostate cancers15. A 2006 study of more that 120,000 people found that taking 400 IU per day of vitamin D lowered the risk of pancreatic cancer by 43%.12 A study involving 1,200 women, published in June 2007, reported that vitamin D at 1,100 IU/day resulted in a 60% reduction in cancer incidence during a four-year clinical trial12. Additional research suggests that vitamin D may play a protective role against cancers of the lung, pancreas, kidney, stomach, esophagus, bladder and rectum, as well as non-Hodgkin’s lymphoma13. In tissue cultures, the vitamin D hormone has been found to

33VI. Vitamin D

induce the death of cancer cells. This positive activity of vitamin D is believed to result from its action as a nuclear transcription factor that regulates cell growth, differentiation and programmed cell death, called apoptosis. In addition, vitamin D appears to regulate many cellular mechanisms central to the development of cancer.

2. Populations at Risk

An estimated one third of healthy young adults do not receive sufficient vitamin D, however, the prevalence of vitamin D deficiency varies by season. According to one study at winter’s end 30% of patients in all age groups exhibited low vitamin D levels. By contrast, the vitamin D deficient population at the end of summer was only 11%. Risk factors for vitamin D deficiency include:

• DarkSkin – High melanin content of dark skin decreases the ability to produce vitamin D from sunlight. According to the National Health and Nutrition Examination Survey (NHANES) III survey, the prevalence of hypovitaminosis D among black women is 42.4% as compared to 4.2% among white women15.

• OlderAge – Beginning around age 50 the body’s capacity to synthesize vitamin D in the skin is lowered. At this same time, the kidneys become less able to convert vitamin D into a useable form. Even prior to age 50, many adults curtail daily milk consumption, and in doing so, they eliminate a source of vitamin D since both soymilk and cow’s milk are fortified with vitamin D15.

• Obesity– When compared to a lean control group, obese individuals present significantly lower vitamin D levels. The likely cause is vitamin D3 deposits in body fat compartments that decrease its bioavailability from cutaneous and dietary sources15.

• LimitedSunExposure– Vitamin D production is curtailed by reduced sun exposure. Sun exposure is limited by factors including spending long periods of time indoors, wearing sunscreen and protective clothing, and living above the 30-degree northern latitudes, where there is less sunlight. Multiple sclerosis, diabetes, and rheumatoid arthritis, as well as breast and prostate cancers, which have been linked to lack of vitamin D, are more common in northern regions where people get less sun15.

• FatMalabsorption– Vitamin D requires some dietary fat absorption so people suffering from diseases and conditions that cause fat malabsorption are at increased risk. Examples include pancreatic enzyme deficiency, Crohn’s disease, cystic fibrosis, celiac sprue, and liver disease. Fat malabsorption is also common when part or all of the intestines are removed, such as in gastric bypass surgery15.

• BreastfedInfants – Human milk does not contain adequate vitamin D, therefore infants who receive nourishment exclusively through breastfeeding often develop vitamin D

34 VI. Vitamin D

deficiency. The American Academy of Pediatrics and the Food and Nutrition Board of the Institute of Medicine recommend daily vitamin D supplementation for all breastfed infants to avoid deficiency15.

Assessment and Treatment Vitamin D deficiency is diagnosed by drawing a serum 25-hydroxyvitamin D or 25-OH D level. [Note: Some practitioners mistakenly order a 1,25-OH vitamin D (calcitriol) test.] Levels should be obtained twice a year to establish a baseline before starting supplementation. For best results, patients should be tested in early spring, when levels are lowest due to reduced sun exposure, and again in early fall when levels are at their peak after summer sun exposure. Avoiding rickets requires a blood level of 10 ng/mL; a level of 30 ng/mL or higher is necessary to produce full health benefits. Experts recommend that patients maintain 25-OH Vitamin D levels between 40 ng/mL and 60 ng/mL year round. The standard treatment recommendation for adults with vitamin D deficiency is supplementation with 1,000 international units (IU) or more daily. Laboratory testing is unnecessary and can be discontinued after a patient achieves a healthy vitamin D level15.

3. Sources of Vitamin D

• Sunlight – In temperate regions during the spring and summer, exposing the face, arms, hands or back without sunscreen to midday sun for only 10–15 minutes twice a week can produce the body’s requirement of vitamin D. Our skin both makes and degrades vitamin D, so if it produces more vitamin D than it needs, the body will simply destroy it, making it is impossible to develop a dangerous level of vitamin D through sun exposure. Despite this, depending on the sun for vitamin D is not recommended. Not only do we know that the ultraviolet rays of the sun have a damaging effect on skin, but the sun’s reliability varies depending on a variety of factors. Fortunately vitamin D is available through other sources16.

• Food – Vitamin D naturally occurs in food sources like fatty fish (such as herring, catfish and salmon), cod liver oil and eggs, but fortified foods provide most of the vitamin D in the American diet. In the 1930s, the U.S. started a milk fortification program to combat rickets, then a major health problem caused by vitamin D deficiency, and the program virtually eliminated this disorder. Today, nearly the entire U.S. milk supply is fortified with 100 IU/cup of vitamin D. Many foods, such as yogurt, margarine, oil spreads, breakfast cereal and bread are also fortified with vitamin D, as are beverages including soymilk, orange juice and other fruit juices. When trying to obtain vitamin D through diet, it is important to realize that dairy products made from milk, such as cheese and ice cream, are generally not fortified. Maximum levels of added vitamin D are specified by law so vitamin D toxicity from food sources is highly unlikely. That said, caution should be applied to the use of cod liver oil. While it is very rich in vitamin D, it also contains high levels of vitamin A, which can weaken bones16.

35VI. Vitamin D

Food Sources of Vitamin D16

Food IU’sperServing

PercentDV*

Cod liver oil, 1 tablespoon 1360 340%Salmon, cooked, 3 oz 794 199%Mackerel, cooked, 3 oz 388 97%Tuna fish, canned in water, drained, 3 oz 154 39%Milk, vitamin D-fortified, 1 cup 120 30%Orange juice, vitamin D-fortified, 1 cup 100 25%Yogurt, fortified with 20% of DV for vitamin D, 6 oz 80 20%Margarine, fortified, 1 tablespoon 60 15%Sardines, canned in oil, drained, 2 sardines 46 12%Liver, beef, cooked, 3.5 oz 46 12%Ready to eat cereal, fortified with 10% of DV for vitamin D, 1 cup 40 10%Egg, 1 Whole 25 6%Cheese, Swiss, 1 oz 6 2%*Based on an RDA of 400 IU

• Supplements– Cholecalciferol, or vitamin D3, is the preferred supplement because it raises serum vitamin D more effectively than vitamin D2 (ergocalciferol). Vitamin D supplements are generally inexpensive and widely available. The typical multivitamin has 400 IU of vitamin D. Some calcium supplements also contain vitamin D. Vitamin D supplementation is contraindicated in a small number of patients. It is not recommended for patients with diseases that cause vitamin D hypersensitivity syndromes (primary hyperparathyroidism), nor is it appropriate for patients with hypercalcemia caused by some of the granulomatous diseases (sarcoidosis, Crohn's disease and tuberculosis)16.

36 VI. Vitamin D

Adequate Intakes for Vitamin D (in IU’s)*

Age Men Women

0-13 200 20014-18 200 20019-50 200 20051-70 400 40071+ 600 600

*AsrecommendedbytheInstituteforMedicineforpreventionofbonediseaseandrickets

Current government guidelines for vitamin D are based solely on the prevention of bone disease and rickets; they do not address treatment of these conditions or consider other disease states. When this is taken into consideration, the average recommended daily amount of 400 IU (the amount contained in most multivitamins or in 4 cups of fortified milk) is too low to provide optimum health benefits. New U.S. dietary guidelines endorse much higher amounts, 800 to 1,000 IU daily, with most scientists currently recommending 1,000 IU be consumed daily to maintain adequate blood concentrations of 25-hydroxy vitamin D and receive health benefits.

The tolerable upper intake level for vitamin D, established by the Institute of Medicine in 1997, is 2,000 IU per day for adults and children over age one and 1,000 IU for infants. In most cases, 1,000 IU of cholecalciferol (vitamin D3) per day is needed to increase levels by 10 ng/mL. Therefore, to treat a vitamin D deficient patient with a level of 10 ng/mL, prescribe 3,000 IU cholecalciferol daily to obtain a level of 40 ng/mL.

Vitamin D toxicity can occur, but most experts agree that it results only after prolonged exposure to more than 10,000 IU per day. Symptoms of toxicity include nausea, vomiting, poor appetite, constipation, weakness, and weight loss. Vitamin D toxicity can raise blood levels of calcium, causing changes in mental status, heart rhythm abnormalities and calcium and phosphate deposits in soft tissues such as the kidneys16.

4. Vitamin D Requirements

Adequate vitamin D intake varies depending on life stage and other factors. Our need for some nutrients, including vitamin D, increases with age, thus extra amounts are recommended for older adults. People with dark skin also require more.

The Institute of Medicine’s guidelines set the adequate intake of vitamin D at 200 IU for healthy individuals under the age of 51. For those aged 51 to 70 the recommended intake is 400 IU per day. After age 70 the recommendation goes up to 600 IU per day16.

37

VII. PHOTOSENSITIVITY

Photosensitivity is an umbrella designation for any adverse reaction to the sun’s rays or artificial light sources. Photosensitive reactions may be phototoxic or photoallergic in nature.

Phototoxicity is common. It causes damage with over exposure to a light source or when the skin contains a photosensitizing agent in a quantity sufficient to increase sensitivity to light. The phototoxic reaction is an exaggerated sunburn characterized by redness and swelling followed by increased pigmentation and peeling. Photoallergy is uncommon. It involves altered reaction that is mediated by the immune system, or is, in essence, an allergy to light. Photoallergic response is characterized by immediate urticaria (hives) or delayed papular (bumpy) or eczematous (red and weepy or scaly) reaction.

Under certain conditions every human being displays photosensitivity. We will all react negatively to radiation when overexposed to the sun; but some people are more sensitive than others. The term photosensitive generally refers to this segment of the population. For the most photosensitive individuals, even small amounts of sun can be very dangerous. Photosensitivity increases all of the risks associated with sun exposure, including sunburn, cosmetic changes, immune system suppression and skin cancer.

What Causes Photosensitivity?

Photosensitivity can be genetic or acquired. It can be caused by environmental factors and/or may be the by-product of certain physiological conditions.

Environmentally, pollution has depleted the ozone layer. The deterioration of this natural atmospheric shield has left us all more vulnerable and led to a general increase in photosensitivity. In addition, we come into contact with more and more photosensitizers on a daily basis. Photosensitizers are substances that absorb UV from the sun or artificial light sources and induce adverse skin responses. These substances can reach us either topically or systemically. Photosensitizing ingredients, for example tars, psoralen compounds and halogenated salicylanilides, are routinely included in a host of everyday health and beauty products (perfumes, moisturizing creams, after-shave lotions, deodorant soaps), as well as in materials that are commonly used in certain industrial and agricultural sectors. Over 400 medications ranging from birth control pills to antibiotics to chemotherapy agents are know to cause photosensitive or photoallergic reactions. (See Appendix B for examples.)

Myth: Over-the-countermedicationsdonotimpactsunsensitivity.Fact: Manyoverthecounterandprescriptionmedications,aswellas certainmedicalconditions,increasesensitivitytothesun.


38

Pigmentation is a major physiological factor in photosensitivity. Pigment provides protection against UV damage; an innate absence or acquired loss of pigmentation equates to greater photosensitivity. Fair skinned individuals (Fitzpatrick Skin types I or II) are naturally photosensitive, as are people who suffer from genetic conditions that preclude or impair pigment production. Pigment-related photosensitivity is acquired when skin destroys melanocytes and the ability to produce pigment.

A variety of diseases and disorders are aggravated by sun exposure and severely exacerbate photosensitivity. Organ transplant patients, patients undergoing Photodynamic Therapy (PDT), those who have had certain aesthetic procedures such as glycolic peels, microdermabrasion, or laser treatments are also photosensitive.

Regardless of the cause, photosensitive individuals must practice daily, year-round sun protection. Both UVA and UVB are known to provoke phototoxic and photoallergic responses, which makes full spectrum protection an imperative. To maintain overall health, avoid skin damage, and prevent skin cancer, it is especially important for photosensitive people to follow these recommendations:

• Apply a full spectrum sunscreen with a sun protection factor of at least 30 or higher.• Make sunscreen a normal part of the morning routine. Re-apply every 2 to 4 hours.• Wear protective clothing, long sleeved shirt and long pants when possible.• Regularly wear a wide brimmed hat and sunglasses with UV protection.• Limit outdoor activity between 10 a.m. and 4 p.m.


39

COMMON PHOTSENSITIZING MEDICATIONS AND CHEMICALS

Class Medication/Chemical Phototoxic PhotoallergicAntibiotics Tetracyclines

(minocycline, doxycycline, tetracycline)Fluoroquinolones(ciprofloxacin, ofloxacin, norfoxacin)

4

4

NSAIDS IbuprofenKetoprofenNaproxen

4

4

4

Diuretics FurosemideHydrochlorothiazide

4

4 4

Retinoids IsotretinoinAcitretin

4

4

Others PsoralenAmiodaroneDiltiazemChlorpromazineQuinidineCoal Tar5-fluorouracil5-aminolevulinic acid

4

4

4

4

4

4

4

4

4

4

4

Sunscreens PABA and derivativesCinnamatesBenzophenonesSalicylates

4

4

4

4

Fragrances Musk ambrette6-methylcoumarin

4

4


40 VII. Photosensitivity

Conditions Caused or Related to Photosensitivity:

1. Non-MelanomaSkinCancerandpre-malignantconditions:A direct cause and effect relationship has been established between ultraviolet light and skin cancer. Melanoma is life threatening and the most common cancer for women age 25-29. It is the second most common cancer for women 30-34. Melanoma has also been reported as having a 50% increase in death rates in men over 50 during the past 15 years17. Photosensitive individuals, ranging from people with fair skin types to organ transplant patients, are at greater risk for skin cancer.

2. Lupus:Lupus is a chronic inflammatory disease that can affect single or multiple organ systems, especially the skin. Exposure to sunlight may result in the development of, or an increase in skin rash; more importantly, it may exacerbate the disease. Patients require complete full spectrum sun protection.

3. ChemotherapyandPostRadiationTherapy: Patients require complete full spectrum protection to help minimize specific drug-induced photosensitive reactions experienced secondary to chemotherapy and tissue damage as a result of radiation therapy.

4. TransplantImmunosuppressedTherapy: Immunosuppressive medications that are required for survival after an organ transplant increase the risk for skin cancer. Organ transplant patients are 65 times more likely to develop skin cancer than the general population. The risk is even greater for patients with other high-risk characteristics, such as fair skin, light eyes, an outdoor occupation, and family or personal history of skin cancer. A high-risk transplant patient may experience repeated skin cancers, resulting in frequent surgeries and an overall risk that one of the cancers will pose a problem or even cause death if left untreated. Patients require complete full spectrum protection from all the damaging rays of the sun.

5. PostLaserSkinResurfacing,Chemical Peels, Microdermabrasion: These procedures render the skin more sensitive. Proper sun protection reduces vulnerability to photodamage and enhances the overall healing process. Without proper sun protection, outcomes may also be less than optimal.

6. FacialCosmeticSurgeryandFacialTrauma: Patients require complete full spectrum protection from the sun’s damaging rays.

7. Vitiligo:A pigmentation disorder in which melanocytes in the skin are destroyed. As a result, depigmented patches of skin appear. A single event, such as sunburn, can trigger this disorder. Treatment therapies for Vitiligo require that patients use complete full spectrum protection.

8. Rosacea:Rosacea is a chronic condition that is aggravated by sunlight. The disease affects the skin of the face. It usually starts with redness on the cheeks and can slowly

41

worsen to include one or more additional symptoms. Patients require full spectrum sun protection and are advised to use non-comedogenic facial products.

9. PolymorphousLightEruption(PMLE):An acquired disease; it is the most common of the idiopathic photodermatoses. PMLE is characterized by recurrent, abnormal, delayed reactions to sunlight ranging from erythematous papules, papulovesicles, and plaques to erythema multiforme–like lesions on sunlight-exposed surfaces.

10.SolarUrticaria:An abnormal reaction to sunlight or artificial light. When exposed to light, the skin cells release potent chemicals (including histamine), causing blood vessels to open and fluid to collect within the skin. The skin feels itchy and has red patches, which may be swollen. These may look like wheals or a nettle rash and can take up to an hour to appear after exposure to light. They come on quickly and settle within a similar period.

11.AtopicDermatitis: A skin disease characterized by areas of severe itching, redness, scaling, and loss of the surface of the skin (excoriation). When the eruption (rash) has been present for a prolonged time, chronic changes occur due to the constant scratching and rubbing known as lichenification (thickening of the skin with accentuation of the skin lines to form a crisscross pattern).


42

Genetic and Congenital Diseases Causing Heightened Photosensitivity:

1. BloomSyndrome:A rare autosomal recessive disorder characterized by telangiectases and photosensitivity, growth deficiency of prenatal onset, variable degrees of immunodeficiency, and increased susceptibility to neoplasms of many sites and types.

2. Cockayne’sSyndrome: A rare inherited disorder characterized by growth retardation, photosensitivity, premature aging and early death. The extent and severity of the clinical symptoms vary in affected individuals. Onset of symptoms in the second year of life is heralded by a scaly erythematous eruption in the sun-exposed areas of the skin that may resolve, leaving hyperpigmentation or scarring.

3. Chediak-HigashiSyndrome: An inherited disorder of the immune system that results in chronic infection, decreased pigmentation in skin and eyes, neurological disease, and early death.

4. Darier’sDisease(aka‘keratosisfollicularis’): A rare genetic disorder that is manifested predominantly by skin changes. Onset of skin changes is usually in adolescence and the disease is usually chronic.

5. Dermatomyositis: A chronic inflammatory disease of skin and muscle that is associated with patches of slightly raised reddish or scaly rash.

6. OculocutaneousAlbinism: An hereditary disorder characterized by deficiency of the pigment melanin in the eyes, skin and hair. The lack of eye pigment causes photophobia (sensitivity to light), nystagmus, and decreased visual acuity.

The Facts of Light V:

• UVA light has been shown to have immunosuppression effects; a direct relationship has been established between these effects and skin carcinogensis in humans.

• Naturally (inherited) dark skin is less prone to melanoma, however artificially acquired dark skin (i.e., a tan) does not afford the same protection.

• The immune system is vulnerable to modification by environmental agents such as UV radiation, which appears to diminish its effectiveness by changing the activity and distribution of the cells responsible for triggering immune responses.

• Skin is more vulnerable to sun damage post surgery or while undergoing treatments such as chemical peels.

• Squamous cell carcinoma is the most common skin cancer in organ transplant patients. • Sunscreen has been proven effective at preventing tumors of squamous cell cancer


43

7. Phenylketonuria: Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the amount of the amino acid phenylalanine to harmful levels in the blood. If PKU is not treated, excess phenylalanine can cause mental retardation and other serious health problems. Children with classic PKU tend to have lighter skin and hair than unaffected family members, because phenylalanine is important for skin pigmentation. Children with the disorder are also likely to have skin disorders such as eczema.

8. Porphyrias:A diverse group of diseases in which the production of heme is disrupted. Porphyria is derived from the Greek word “porphyra”, which means purple. When heme production is faulty, porphyrins are overproduced and lend a reddish-purple color to urine. All forms of porphyrias are inherited. The key clinical features are skin sensitivity to sunlight and/or by intermittent acute attacks of abdominal and nerve pain.

9. Rothmund-ThomsonSyndrome: An hereditary disease characterized by progressive degeneration (atrophy), scarring and abnormal pigmentation of the skin together with growth retardation, premature baldness, juvenile cataracts, depressed nasal bridge, and malformations of the teeth, hair, and bone.

10.Xerodermapigmentosum: A genetic disease that renders the body unable to repair ultraviolet damaged DNA. It is characterized by such extraordinary sensitivity to sunlight that it results in the development of skin cancer at a very early age. Children with xeroderma pigmentosum (XP) can only play outdoors safely after nightfall. They have been called midnight children, the children of the dark, the children of the night and, perjoratively, vampire children.


44

VIII. THE CHEMISTRY OF SUNSCREEN

All it takes is one trip to the sunscreen aisle of the local drug store to realize not all sunscreens are created equal. But, with so many labels making similar claims, how does one judge? The best way is to know a little something about the chemistry behind this class of products.

Seventeen active ingredients are currently FDA-approved for sunscreen use in the United States. They fall into two categories: physical blockers (a.k.a. inorganic physical ingredients) and chemical absorbers (a.k.a. organic chemical ingredients). Physical blockers work by scattering and reflecting UV radiation; chemical absorbers work by absorbing UV radiation (and emitting the absorbed energy as heat) before it can penetrate the skin.

Each ingredient has demonstrated some level of effectiveness, but all are subject to some degree of limitation. No single ingredient provides every benefit possible. Some protect against a larger range of the light spectrum than others. Some have been associated with skin irritation. Some feel more comfortable. Some chemical absorbers become unstable and lose their protective capability after a certain time in the sun; others can penetrate the epidermis and generate free-radicals, leading to cell damage. The sunscreens we see on store shelves are actually formulations that, with varying degrees of success, combine actives with a variety of inactives in an attempt to increase efficacy and achieve cosmetic desirability.

This section provides some basic information about the most common ingredients.

PHYSICAL BLOCKERS:

Physical blockers fall into three categories: 1. Direct physical blockers, 2. Indirect blockers that assist by increasing distribution of direct blockers, and 3. Polymers, often starch derived, that substantially increase the effective length of the

pathway that the sun’s rays must travel to reach the skin.

Of primary importance is that these physical protectants be incorporated at adequate concentration to afford complete protection for extended periods.

Direct Physical Photoblockers

Most of the physical photoblockers are metal oxides (iron, zinc, titanium, etc.) that occur naturally, while some, such as bismuth, are man-made. In addition to their photoprotective attributes, these substances also assist in preventing windburns and skin damage from wind driven microparticles of dirt and grime.

An additional significant property of physical blockers is their ability to offer a defense against infrared (“heat”) rays by two distinct means. First, particles large enough to be visible (i.e. reflect visible light) will also reflect and refract the infrared waves most harmful to skin (760nm – 1,800nm).

VIII. The Chemistry of Sunscreen

45

Second, regardless of their particle size, these metal-based materials act as a “heat sink” and thereby reduce the heat effect on the skin.

Threeimportantphotoprotectiveblockersaretitaniumdioxide,zincoxide,andironoxides.

1. Titanium Dioxide:This white pigment powder is widely used in cosmetics. The purpose of large particle titanium dioxide is to give opacity and lighten (or whiten) the color of the products containing it. Opaque titanium dioxide highly reflects and strongly scatters all UV and visible rays. It also reflects much of the skin damaging infrared waves, which keeps the skin cooler, reducing “heat” damage and its subsequent photoaging.

To photo-stabilize titanium dioxide, it must be micro-coated with its own protectant such as silicone or aluminum oxide. Alternatively, breakdown is inhibited by incorporating other appropriate blockers together with titanium dioxide since titanium dioxide spreads poorly on the skin. Micro-coating the titanium dioxide is also a common way to achieve cosmetic elegance and usefulness; designing a vehicle to assure good, even application to the skin is essential. Large particle titanium dioxide products produce a very white, opaque appearance when applied on the skin, but submicronizing titanium dioxide powder creates small particles that absorb visible light and are invisible on the skin while enabling products to protect the skin from most UVB and some UVA.

Transparent (sub-micronized) titanium dioxide works by absorbing, reflecting and scattering UVB and some UVA rays. However, protection against UV, visible and infrared is significantly limited when sub-micronized titanium dioxide is the primary protectant.

2. Zinc OxideZinc Oxide has been known and used topically for centuries as a skin protectant and wound healing adjuvant and is a recognized mild antimicrobial agent. More than 50 years ago, zinc oxide was indicated as a block for ultraviolet light (UVB/UVA). Like titanium dioxide, it also reflects infrared from the skin. Unlike titanium dioxide, it has a much higher ability to protect in the long UVA range (300 – 400 nm), and it absorbs- rather than scatters most UVA. Thus, used in combination with titanium dioxide, ultrafine zinc oxide “closes the window” in the UVA range. Zinc oxide both complements titanium dioxide’s protective abilities and extends photoprotection to the skin where titanium dioxide is insufficient. The optimal particle size range for ultraviolet-blocking zinc oxide (without blocking visible wavelengths) is approximately 80 to 150 nanometers

3. Iron OxidesWe most commonly encounter iron oxide either as rust on exposed iron or in cosmetics, where it is used to give the cover-up color desired. While not approved by the FDA as an active ingredient in sunscreens, many companies use iron oxides in sunscreen products. Cosmetic iron oxides are man-made to obtain very high purity.


46

Iron oxide pigments for cosmetic use are micronized powders. By controlling the purity, particle size, temperature and rate of drying during manufacture, they become available in a number of shades and tones of red, yellow, black and brown (and blends of these basic colors). If incorporated at adequate concentration and when properly dispersed in well-designed vehicles, these cosmetic pigments not only add color to the lotion (or cream, powder, etc.), but also significantly contribute to protecting the skin from multiple wavelengths of light.

Ultra-submicronized iron oxides offer the advantage of protecting against visible light waves while adding little color to the finished product. Thus, higher levels of infrared protecting iron oxide can be used without compromising the cosmetic elegance and shade of the final preparation. Submicronized iron oxides are reported to considerably block ultraviolet rays, further complementing a product’s primary UV blocking agents.

Indirect Physical Blocker Aids

Examples of these particles include natural talc or mica. They are usually flat and oval in shape. These particles are very small, although they are much larger than direct physical blockers. When combined with physical blockers, a portion of very small physical blocker particles will coat the larger flat blocker aids. Because they are flat and smooth, the coated blocker aids will easily slide over each other and overlap to effectively increase protective coverage on the skin.

Polymers

Polymers can be natural substances from plants; modified semi-natural, animal derived (modified chitin, from the “shells” of shrimp etc. is commonly employed); or synthetic substances such as micronized nylon. Certain polymers, when carefully formulated into a photoprotective preparation, create a “cage” structure that forces ultraviolet and visible rays to follow a maze rather than directly reaching the skin. This protracted route helps increase protection by either preventing some rays from reaching the skin (or reaching the skin with greatly reduced energy) or by increasing the contact time between the rays and the organic filters/physical blockers.

By themselves, such polymers (which incidentally also improve the feel of the cosmetic finished product on the skin) provide little to no useful skin photoprotection, but they do help to defend the skin from wind and wind-blown dirt and grime pollution particles. In the presence of active photoprotective agents, these polymers can increase the Sun Protection Factor (SPF) by 3 to 5 units.

CHEMICAL ABSORBERS:

Chemical absorbers are usually soluble in oils or water. They filter UVB and/or UVA radiation to varying efficiency. No chemical sunscreen filter completely absorbs the UVB and/or UVA rays from the skin. Further, the actual protection offered by any and all sun-protective products


47

relates directly to their level of concentration, how long they remain stable when exposed to sun, the film thickness applied to the skin, as well as the careful, total coverage of the exposed skin sites.

Themostcommonchemicalabsorbersusedinsunscreensinclude:

Octyl Salicylate Salicylates are the oldest class of sunscreens, with octyl salicylate being the most widely used. While it is strictly a UVB absorber, and a weak one at that, it offers several positive qualities, including that it is virtually nonirritating and nonsensitizing to skin, and cosmetically, it is an easy to handle emollient “oil” that acts as a good solvent (solubilizer) for other, solid organic sunscreens, such as the benzophenones.

Octyl Dimethyl PABA (Padimate O)This oil-like UVB absorber is the most efficient for this ultraviolet range, absorbing best at the maximum sunburn frequencies (310nm – 312nm). It was the most popular UVB sunscreen in the United States, but adverse (perhaps unfounded) reports have reduced its use. Padimate-O is a PABA (Para Amino Benzoic Acid) derivative, but it is quite distinct. Today’s purified material is essentially free of PABA.

Octinoxate (Octyl Methoxycinnamate)Currently, this oily liquid is the most widely utilized organic UVB absorber in the world. It is second in efficiency to Padimate-O, but offers broader protection (300nm –315nm) in the sunburn region of UVB. It has a very good safety record and is relatively easy to use in formulations. Additionally, it is moisturizing and water insoluble, adhering tenaciously to the skin.

Meradimate (Menthyl Anthranilate)An old and safe but overall weak absorber, menthyl anthranilate absorbs moderately in the UVB range from about 300nm and somewhat more strongly into the UVA range (up to about 340nm). It can somewhat enhance the UVB and lower (320nm to 340nm) UVA absorption of more active absorbers.

Oxybenzone (Benzophenone-3) and Sulisobenzone (Benzophenone-4)These are closely related solid (powder) absorbers. Oxybenzone is water–insoluble, while the acid form, sulisobenzone, can be made soluble in water when it is neutralized. While these compounds are classified as UVA absorbers they are also UVB absorbers. Overall, they offer only moderate protection through both the UVB range and part of the UVA range (320nm – 360nm). They are quite stable and can enhance effectiveness of stronger UVB absorbers.


48

Avobenzone (Parsol®1789)This solid (powder) absorber exhibits marginal UVB and lower (320nm – 330nm) UVA absorption. It gives good UVA absorption from about 330nm to 340nm and very good absorption in the UVA range up to about 370nm, where it rapidly loses effectiveness. Because of its irritation potential, the allowed concentration level in the U.S. is low, limiting the actual level of protection obtained. In addition, avobenzone is reported to be photo-unstable. It can convert to its inactive form in the presence of UV radiation and readily loses more than one-third of its active form (negating its photoprotective ability) rather quickly. Therefore, avobenzone (Parsol 1789) is a useful, but limited, UVA protector. Its usefulness can be enhanced when combined with UVB absorbers and physical protectors, such as zinc oxide, but without careful formulation, it may decrease the protective ability of UVB sunscreens. The combination of avobenzone with zinc oxide is presently not allowed by the tentative FDA monongraph; evaluation by the FDA to allow this combination is underway.

OctocryleneAn emollient, water resistant UVB/UVA absorber. While octocrylene is a relatively weak sunscreen, it gives some protection in the UVB and lower UVA range (320 – 350 nm). Most important, octocrylene is a very stable absorber and both protects and augments other UV absorbers while improving their uniform skin coating.

FDA APPROVED ACTIVE INGREDIENTSSunscreenactiveIngredients:

Aminobenzoic acid (PABA) up to 15 percentAvobenzone up to 3 percentCinoxate up to 3 percentDioxybenzone up to 3 percentEcamsule up to 10 percentEnsulizole up to 4 percentHomosalate up to 15 percentMeradimate up to 5 percentOctinoxate up to 7.5 percentOctocrylene up to 10 percentOctyl salicylate up to 5 percentOxybenzone up to 6 percentPadimate O up to 8 percentSulisobenzone up to 10 percentTitanium dioxide up to 25 percentTrolamine salicylate up to 12 percentZinc oxide up to 25 percent


49

CELL PROTECTANTS

Sunscreens may also contain substances that help protect our skin from other unseen damage from the sun. This section discusses these substances, known as cell protectants.

BackgroundUVA radiation penetrates deeply into our skin and initiates oxidation processes at the cellular level. Exposure to UVA causes pigmentation changes such as tanning or burning. A variety of free-radical oxygen species, including superoxide (*O2) and hydroxy radicals (*OH) are released via UVA induction and cellular damage then occurs, particularly by membrane lipids’ peroxidation. Hydrogen peroxide may also form and add to cellular damage.

The primary action of UVA is to add energy to molecules in our skin, including ubiquinone (Coenzyme Q10), that go on to interact with oxygen to produce the highly reactive oxygen forms mentioned above. These “oxygen” moieties degrade DNA in our cells.

Evidence of UVA damage becomes visible first as sunburn (where it adds to UVB burning), then inflammation and skin darkening, and later as photoaging and skin cancers. The Skin Cancer Foundation has reported that depletion of vitamin A in the skin by UVA exposure may contribute to both photoaging and cancers of the skin9.

Supplementary cellular protectants are not intended to act as primary UV absorbers (though some may exhibit slight absorption within the UVB – UVA spectrum). Rather, they act to prevent damage to the cells directly and indirectly.

Below is a partial list of common cellular protectants used in sunscreens. This is not an all-inclusive list, but rather, a review of cell protectants with different modes or sites of active protection.

Vitamin EIn its pure active “natural “ state, as tocopherol, vitamin E protects from oxidizing, but it is too reactive to retain adequate activity within the skin when topically applied. Fortunately, our skin can metabolize more stable forms of vitamin E to release tocopherol where it is needed. Tocopheryl acetate and tocopheryl linoleate are among the more popular forms used in sunscreens. As an oil-soluble antioxidant, it gives considerable protection to our skin’s cells. Vitamin E “breaks” the chain-reaction of free- radicals before they can cause lipid peroxidation-induced destruction of the cellular membranes; however, it requires a regeneration agent, a substance that prevents it from being rapidly depleted. Vitamin C (see below) is one such regeneration agent.


50

Vitamin C (ascorbic acid)Human beings do not produce vitamin C themselves. We rely entirely on our dietary intake for our vitamin C. Vitamin C is normally deposited in the skin and is an essential part of the antioxidant brigade to protect skin against free radical assault from UV light.

Vitamin C is one of the most effective antioxidants available and is used in sunscreen to regenerate the lipid-soluble vitamin E (so that it retains its cellular membrane protective activity). Vitamin C is available in many forms, some of which are water-soluble (ascorbyl acid phosphate, for example), while others are lipid-soluble, such as ascorbyl palmitate. Ascorbyl palmitate, topically applied, has also been reported to exhibit some protection against UVB burns and has anti-inflammatory activity. Combinations of vitamin C compounds with vitamin E appear to offer greater protection against cellular insult from UVB and/or UVA exposure than either antioxidant alone. Additionally, vitamin C moderately protects against UVB photodamage as well as UVA-promoted phototoxic responses18.

Vitamin ANormally found in the skin as retinyl palmitate, vitamin A is the dominant vitamin of the skin because it has a fundamental role in the control of normal activities of skin cells. It also is of great importance in controlling normal activities of the DNA of the nucleus of the cell as well as the mitochondria. Vitamin A is extremely sensitive to sunlight and particularly to UVA (315-400nm) light19.

Beta–Carotene (B-Carotene)This precursor of vitamin A, a lipid-soluble (i.e. oil soluble) yellow–orange/orange-red pigment, is found in most vegetables. Beta-Carotene is an excellent quencher of singlet oxygen (free radical) as well as free radicals that participate in lipid peroxidation. B-Carotene has been reported to be of value in the treatment of erythropoietic protoporphyria (EPP), a disease that causes photosensitivity to upper UVA and sections of visible light (380nm – 560nm). Additionally, there is evidence that Beta-Carotene inhibits UV’s promoted carcinogenesis.

Anthocyanins/ProanthocyaninsThese bioflavanoid-like antioxidants are found in vegetation such as grapes and pine bark (The Maritime Pine yields a highly active proanthocyanidin offered under the trademark Pycnogenol). These compounds are among the most active free-radical quenchers known. Anthocyanins increase the action of ascorbates (vitamin C) and supplement the protective qualities of tocopherol (vitamin E). Published reports describe the ability of these highly specialized antioxidant bioflavanoids to not only potentiate vitamin C, protect cells and collagen tissue, but to strengthen blood vessels and maintain capillaries18.

SeleniumNumerous medical, pharmaceutical and nutritional publications describe the ability of selenium, in very low doses, to help prevent cancer, including skin cancer, act as an anti-inflammatory, and aid in cellular DNA repair. It has also been reported that selenium reduces the reactivity of skin


51

cells to UV exposure. Complex selenium compounds, topically applied in concentrations of less than 0.05% (selenium), significantly reduce UV skin damage (manifested as less inflammation, less pigmentation, and retardation of and diminished levels of skin cancer)20.

ChelatesChelates are compounds that bind metals, particularly iron, and remove them from interacting with other materials. Some chelates are formed naturally, others are synthesized. Iron chelators protect against cellular damage from free-radical(s) oxygen. A few chelating compounds are ortho-phenanthroline, edetic acid (and its salts/derivatives) and dipyridylamine. Topical chelate application prior to UV exposure is reported to reduce and/or delay visible skin wrinkling caused by UV exposure, as well as tumor formation.

Miscellaneous Photoprotective /Cell AidsSome materials indirectly protect the skin cells from light wave damage by either maintaining the UV absorbers on the skin surface, such as octyldodecyl neopentanoate, or by forming a matrix or maze-like film that tightly bonds to the skin surface. These materials, such as acrylates/octylpropenamide copolymer and aluminum starch octenylsuccinate, significantly lengthen the pathway of light trying to reach skin, thereby reducing the light’s ability to damage skin cells.

Other Factors That Impact Product Quality

Film Formation

A sunscreen product will perform at its best only when the active ingredients are dispersed on the skin as evenly as possible. When an adequate amount is applied and spread thoroughly enough to totally cover the skin, the product should create a film that has enough structure to coat the peaks and valleys of the skin and maintain that coverage.

Dispersing Inorganic UV Filters

Dispersing inorganic UV filters (physical blockers) and maintaining the even coverage required for optimum effectiveness requires the active ingredients to have the proper degree of dispersability. Titanium dioxide and zinc oxide are available pre-dispersed or as a dry powder.21 When introduced into the product in powder form, titanium dioxide and zinc oxide should have a uniform surface coating to maximize product stability and minimize particle agglomeration that is typical with uncoated material.

Photostability and Organic Filters

When exposed to UV light, some organic UV filters (chemical blockers) are known to undergo chemical changes that compromise their ability to protect the skin. Octinoxate and avobenzone


52

are two examples of chemical blockers that breakdown rapidly in sunlight; especially when combined in the same product. Products must be carefully formulated to insure photostability. An unstable filter can maintain its integrity only if it is paired with the proper complementary filter (e.g. octocrylene stabilizes avobenzone). Several newer UV filters that have yet to be approved for use in the United States are reported to boost photostability.

Combining UV Filters

When used as a sole active titanium dioxide can achieve higher SPF values (UVB protection) as opposed to combination with other active ingredients. To obtain broad-spectrum protection, titanium dioxide is many times combined with zinc oxide. This combination increases the level of UVA protection. Another combination strategy is to use both oil dispersed and water dispersed TiO2 in the same formulation.21 This approach of combining oil and water dispersions helps to increase the efficacy and stability of the product.

Water Resistance

In order to be considered water-resistant, once a product has dried on the skin it must 1) contain a low concentration of hydrophilic emulsifiers so it will not re-emulsify in contact with water; 2) maintain a filmy texture on the skin that cannot be easily rubbed off by water; and 3) have active ingredients dispersed evenly throughout the film.

The film deposited on skin by water in oil emulsion can be expected to be resistant to re-emulsification, since oil is the external phase of the emulsion and such emulsions employ predominantly hydrophobic emulsifiers. Silicone oils aid water resistance in two ways: the oils themselves are inherently hydrophobic, and they also have very good spreading properties, which assist in formation of a coherent continuous film. Certain types of emulsifiers can impart water resistance.21

Aesthetic Appeal

No product is effective if no one wants to use it. When consumers apply something to their skin they want it to look and feel good. They demand cosmetic elegance, and inorganic sunscreen dispersions offer the transparency they desire.


53

The Future of Sun Protection:

Botanical-Based Photoprotectants

For those interested in the future, the promising work being done around botanical-based photoprotective actives is an area worth watching. This emerging class of ingredients shows potential for strengthening the skin’s immune response to photodamage and reversing residual damage from past UV exposure.

Carotenoids are antioxidants that are found in various plants, but are particularly abundant in the micro algae Dunaliella. In vitro studies have shown one carotenoid, phytoene, to absorb light in the UVB range, while another, phytofluene, absorbs in the UVA range. Both have been demonstrated to protect against oxidative damage and inflammation, and to inhibit melanin synthesis in skin exposed to UVA radiation22.

A University of Maryland study showedbranextractsknown as inositol and inositol hexaphosphate to be capable of protecting human skin cells and the skin of cancer-prone mice from UVB radiation. They also proved effective at preventing reactive molecules from injuring DNA22.

Gamma oryzanol, which is highly resistant to UV light, is a natural sunscreen enhancer. Already in use as a UVA/UVB filter in Europe, this ricebran derivative displays a powerful antioxidant effect against UV radiation when combined with tocopherol22.

While not a sunscreen, research at Johns Hopkins University has shown that broccolisproutextractcan work inside skin cells to boost enzyme production and protect against UV radiation. Erythema was significantly reduced when the skin of laboratory mice and human volunteers was treated with the broccoli sprout extract sulforaphane22. Significantly, the effect lasts for several days, even after the extract has vanished from the skin surface.

Joint research at the University of Washington and Rutgers University to study the effects of topicalcaffeineon UV exposure has led to preliminary suggestion that caffeine can reduce UV absorption in the skin and inhibit the formation of UV-induced skin cancers22. Caffeine and caffeine sodium benzoate applied to mouse skin after UVB exposure resulted in a significant decrease in UV-induced roughness and wrinkles, and promoted apoptosis of DNA damaged cells. A separate animal study suggested that caffeine in combination with exercise may further boost its cancer-fighting protection.

On the Horizon: Soft Coral from the Red Sea

In March 2009 The Translational Oncology Journal published a study demonstrating that sarcophine-diol, a modification of sarcophine, a natural marine product derived from Red Sea soft coral, shows incredible potential in both the prevention and treatment of certain skin cancers. Using sarcophine-diol on human epidermoid carcinoma cells, researchers at


54

South Dakota State University were able to reduce the life span of cancer cells. In addition, sarcophine-diol arrested and limited the continued growth of cancer cells. The higher the dose of sarcophine-diol and the longer it was applied, the greater its positive effects lasted. While some healthy cells were affected, significantly more damage was done to skin tumor cells, causing an orderly death of cancer cells23. The finding is important as some currently available treatment therapies attack and kill not only cancerous cells but healthy cells as well.

While more studies are needed to fully understand how sarcophine-diol works, its potential as a chemotherapeutic and chemopreventive agent are welcome signs. If the findings hold up, they will offer great promise for advances in skin cancer prevention and treatment. The work can also pave the way for a new family of sun care ingredients.

Nanoparticles: Are They Safe?

By the currently accepted definition, a nanoparticle is a small particle with at least one dimension, but usually more, less than 100 nanometers in length. A nanometer is one billionth of a meter. A consensus exists that physical blockers like titanium dioxide (TiO2) and zinc oxide (ZnO) can provide effective, comprehensive protection as sunscreens. For years, however, consumers did not favor products containing these ingredients because they formed an unattractive white coating on the skin. Today, due to nanotechnology advances, titanium dioxide and zinc oxide based products have become far more desirable.

The ability to use nanosized (i.e. very small) particles of titanium dioxide and zinc oxide allows for increased absorption and has resulted in more transparent products that eliminate the unsightly white coating. The result is a better and more elegant product, but critics have raised concerns that not enough is known about how nanoparticles behave. They worry that nanoparticles could be absorbed through the skin into the bloodstream and create unintended health risks. From a common sense standpoint, they have raised a valid question, but little or no evidence exists to support fears that the nanoparticles used in sunscreens do penetrate into or through human skin. An underlying reason for this is that nanoparticles are naturally prone to tightly bonding together, causing them to act as larger aggregates rather than as separate, individual fine particles. The force required to break aggregates into component particles is far greater than any force applied during the sunscreen manufacturing or application process.

Fine particle grade TiO2 and ZnO have been integrated into cosmetic products for nearly 20 years. Extensive safety testing has been conducted, and results have been independently reviewed by various organizations and regulatory bodies. Evidence from study after study has consistently shown that insoluble nanoparticles, such as those used in inorganic sunscreens, do not permeate human skin. German and Australian health authorities have formally accepted these findings and acknowledged that UV attenuation forms of TiO2 used in sunscreens do not pose any health risk. In a 2007 assessment, the European Union found no evidence of nano-scale particles absorbing through pig skin (the most appropriate substitute for human skin), healthy human skin, or the skin of patients suffering from skin disorders.


55

The Enviromental Working Group (EWG), a U.S. based non-profit organization that conducts independent research to protect human health and the environment, looked at nanotechnology as part of its 2009 sunscreen investigation. Asserting that “no one has taken a more expansive and critical look …at the use of nanoparticles in cosmetics and sunscreens, including the lack of definitive safety data and consumer information on these common new ingredients,” the EWG researchers surprised themselves by deciding that on balance, zinc and titanium-based formulations are among the safest, most effective sunscreens on the market based on available evidence24.

After reviewing scientific publications, government safety assessments, and 16 peer-reviewed studies on the penetration of zinc and titanium nanoparticles through skin, EWG concluded that the “current weight of evidence suggests that these nanoparticles do not penetrate through the thickness of the outer stratum corneum and epidermis to the living tissue below.” They further determined that compared to sunscreens with zinc and titanium, sunscreens without zinc and titanium lead to an average of 20% more UVA radiation exposure, and that chemical absorber-based alternatives commonly contain ingredients that can absorb into healthy skin and cause allergic reactions, often don’t work, break down soon after application, and only marginally protect against UVA protection24.


56

Autho

rSk

inType

Con

clusions

ParticleSize

ParticleCoatin

gW

u 20

09pi

g sk

in in

-vitr

o an

d in

-viv

o, h

airle

ss m

ouse

sk

in in

-viv

o

In-v

itro

pig-

-no

pene

tratio

n of

stra

tum

cor

neum

. In-

vivo

pig

-- p

enet

ratio

n to

dee

per l

ayer

of e

pide

rmis

af

ter 3

0 da

y ex

posu

res.

Hai

rless

mic

e--A

fter 6

0 da

y ex

posu

res

skin

pen

etra

tion

to re

mot

e tis

sues

and

si

gns

of o

rgan

dam

age,

incl

udin

g in

crea

sed

orga

n w

eigh

ts. 1

of t

he 6

type

s te

sted

pen

etra

ted

the

brai

n.

varie

ty o

f siz

es 4

to 9

0 nm

, ru

tile

and

anat

ase

all p

artic

les

wer

e un

coat

ed

Nan

oDer

m

2008

pig

skin

, hum

an

skin

in-v

itro,

hum

an

skin

tran

spla

nted

to

imm

unod

efici

ent m

ice

TiO

2 was

gen

eral

ly d

etec

ted

on to

p of

the

stra

tum

co

rneu

m a

nd to

pmos

t lay

ers

of th

e st

ratu

m c

orne

um

disj

unct

um fo

r hea

lthy

skin

. Pen

etra

tion

via

mec

hani

cal a

ctio

n an

d no

diff

usiv

e tra

nspo

rt ta

kes

plac

e.

20 n

m b

y 10

0 nm

3 fo

rms

of T

iO2 e

xtra

ct-

ed fr

om s

unsc

reen

Mav

on

2007

hum

an v

olun

teer

s, a

nd

in-v

itro

hum

an s

kin

Pen

etra

tion

to u

pper

laye

rs o

f stra

tum

cor

neum

. No

TiO

2 in

folli

cles

, via

ble

epid

erm

is o

r der

mis

.su

nscr

een

with

20

nm T

i tri

met

hylo

ctyl

sila

ne

Gam

er

2006

pig

in-v

itro

Alm

ost a

ll Ti

O2

reco

vere

d by

was

hing

ski

n sa

mpl

e.

No

pene

tratio

n of

stra

tum

cor

neum

.30

*60*

10 n

msi

lica

or m

ethi

cone

Men

zel

2004

pig

in-v

itro

Par

ticle

s in

/on

stra

tum

cor

neum

; min

imal

pen

etra

tion

into

stra

tum

gra

nulo

sum

. No

pene

tratio

n in

to li

ving

sk

in.

45-

150

nm n

eedl

esno

info

rmat

ion

Got

tbra

th

2003

hum

an v

olun

teer

sN

o pe

netra

tion

of p

artic

les

beyo

nd u

pper

laye

rs o

f st

ratu

m c

orne

umTi

O2 f

rom

sun

scre

enno

info

rmat

ion

Sch

ulz

2002

hum

an v

olun

teer

sN

eith

er s

urfa

ce c

hara

cter

istic

s, p

artic

le s

ize

nor

shap

e of

the

mic

roni

sed

pigm

ents

resu

lt in

any

der

mal

ab

sorp

tion

of th

is s

ubst

ance

. Mic

roni

sed

titan

ium

di

oxid

e is

sol

ely

depo

site

d on

the

oute

rmos

t sur

face

of

the

stra

tum

cor

neum

and

can

not b

e de

tect

ed in

de

eper

stra

tum

cor

neum

laye

rs, t

he h

uman

epi

derm

is

and

derm

is.

3 di

ffere

nt s

ize/

coat

ing/

shap

e co

mbi

natio

ns1

type

coa

ted

with

tri

met

hylo

ctyl

sila

ne

(20n

m),

1 w

ith a

lum

i-nu

m a

nd s

ilico

n (1

0-15

nm

), 1

with

alu

min

um

and

silic

a (1

00 n

m)

Pflü

cker

20

01hu

man

ski

n, in

-viv

oM

icro

nise

d tit

aniu

m is

sol

ely

depo

sitiv

e on

the

oute

rmos

t sur

face

of t

he s

tratu

m c

orne

um a

nd c

anno

t be

det

ecte

d in

dee

per s

tratu

m c

orne

um la

yers

, the

ep

ider

mis

or d

erm

is.

3 su

nscr

eens

-T80

5, E

usol

ex

T-20

00, a

nd T

iove

il A

Q (s

ize

= 20

cub

es a

nd 1

00 n

m n

eedl

es).

Par

ticle

s ag

glom

erat

ed.

each

was

coa

ted

with

S

i or S

i+A

l

Dus

sert

1997

hum

an in

vitr

oP

enet

ratio

n lim

ited

to u

pper

laye

rs o

f stra

tum

co

rneu

m50

- 10

0 nm

no in

form

atio

n

Lade

man

19

99hu

man

ski

n in

-viv

oTh

e am

ount

of T

i02 f

ound

in a

giv

en h

air f

ollic

le

was

less

than

1%

of t

he a

pplie

d to

tal a

mou

nt o

f su

nscr

eens

. A p

enet

ratio

n of

mic

ropa

rticl

es in

to v

iabl

e sk

in ti

ssue

cou

ld n

ot b

e de

tect

ed.

UV-

Tita

n M

160

(150

-170

nm

)A

l and

ste

aric

aci

d

Tan

1996

hum

an in

-viv

o13

eld

erly

hum

an v

olun

teer

s ap

plie

d su

nscr

een

for 2

to

6 w

eeks

. Slig

ht a

nd n

on-s

igni

fican

t inc

reas

e in

TiO

2 in

the

epid

erm

is a

nd d

erm

is.

10-5

0 nm

suns

cree

n

TIT

AN

IUM

DIO

XID

E (T

iO2)

PHYSICAL INORGANIC SUNSCREEN FILTERS:


57

Autho

rSk

inType

Con

clusions

ParticleSize

ParticleCoatin

gK

uo 2

008

hairl

ess

mou

se in

-vitr

oZn

O c

oate

d w

ith w

eak

acid

pen

etra

tes

the

skin

. The

se

coat

ings

ext

ract

ed li

pid

from

the

stra

tum

cor

neum

, w

hich

allo

ws

mor

e pa

ssag

e.

Nan

osca

le z

inc

coat

ed w

ith e

than

ol

or o

leic

aci

d

Aci

dic

coat

ings

(o

leic

aci

d an

d et

hano

l) w

hich

diff

er fr

om th

e in

ert c

oatin

gs u

sed

in

suns

cree

ns.

Zvya

gin

2008

hum

an s

kin,

in-v

ivo

and

in-v

itro

ZnO

pre

dom

inan

ly re

mai

ned

on th

e to

pmos

t lay

ers

of th

e s

tratu

m c

orne

um, N

o pe

netra

tion

of Z

nO-n

ano

into

the

cells

or e

xtra

cellu

lar s

pace

was

obs

erve

d.

"The

form

of n

ano

zinc

stu

died

her

e is

unl

ikel

y to

re

sult

in s

afet

y co

ncer

ns."

15-3

0 nm

no in

form

atio

n

Cro

ss 2

007

hum

an s

kin

in v

itro

nano

parti

cle

Insi

gnifi

cant

incr

ease

in Z

nO re

adin

g ep

ider

mis

(<

0.03

%).

No

parti

cles

in lo

wer

stra

tum

cor

neum

or

via

ble

epid

emis

. Con

clus

ion

that

"min

imal

na

onpa

rticl

e pe

netra

tion

occu

rs."

15-3

0 nm

silic

onat

e co

ated

, and

Zi

nCle

ar c

omm

erci

al

suns

cree

n (n

o co

atin

g in

fo)

Gam

er

2006

pig

in-v

itro

Alm

ost a

ll Zn

O re

cove

red

from

sur

face

laye

rs, a

mou

nt

in d

eepe

r lay

ers

was

sim

ilar t

o un

treat

ed a

nd c

ontro

l sa

mpl

es.

80

nm, w

ith 9

0%

<160

nm

unco

ated

Dus

sert

1997

hum

an s

kin

in v

itro

Pen

etra

tion

limite

d to

upp

er la

yers

of s

tratu

m

corn

eum

20-2

00 n

m

Piro

t 199

6hu

man

ski

n in

vitr

oZn

O p

enet

ratio

n of

0.3

6%"m

icro

fine"

no in

form

atio

n

ZIN

C O

XID

E

PHYSICAL INORGANIC SUNSCREEN FILTERS (Continued):


58

Fallene products are the only sunscreen products on the market that offer total light spectrum protection. Many sunscreens offer only “broad-spectrum” UVA/UVB protection. This distinction is important not only for people with photosensitive medical conditions, but also for anyone interested in maintaining a healthy immune system and preventing skin cancer. The term “broad-spectrum” signifies that protection crosses beyond the UVB spectrum (280-315nm) into the UVA spectrum (315-400nm), but “broad-spectrum” products do not cover the entire UVA spectrum; they offer only partial protection from UVA rays in the 340-400 nm range. For protection in the 280 to 400 nm range, The Melanoma Letter has reported on the effectiveness of high SPF products containing UVB absorbers and zinc oxide or titanium dioxide, avobenzone, or other benzophenones9. FalleneproductshaveSPFratingsashighas65andusebenzophenone-3andtitaniumoxideandzincoxide.

While efficacy is certainly of primary importance, it is not the only criteria consumers apply when selecting a sunscreen. They are also interested in the look and feel of a product, and increasingly, are concerned about the risks associated with certain ingredients, both to human health and the environment.

Fallene products are formulated to look and feel elegant; some can even be used in place of liquid foundation. They are fragrance-free, PABA-free and do not absorb into the bloodstream as other products often do. As Wendy Gordon, general manager of National Geographic’s The Green Guide, has pointed out, titanium dioxide and zinc oxide sunscreens will protect against UVA radiation “and leave no trace on the environment.”

Fallene’s Total Block® lotions are also the only products that contain selected photoprotective and cellular protective agents from every category of beneficial substances for the skin. This means that in addition to sunscreen capabilities, Total Block® products are unique in their ability to prevent photo and cellular damage to the skin, regardless of the source: airborne pollutants, wind, damaging effects of radiation.

Tinted/Cover-Up SPF 60 and Clear SPF 65

These lotions are the most protective sunscreen products offered, and they are unique in their ability to protect the skin from the full light spectrum and prevent cellular environmental damage to the skin, regardless of the source of these pollutants. They are formulated to include photoprotective and cellular protective agents from every category of beneficial substances for the skin. Both Tinted SPF 60 and Clear SPF 65 are fragrance free, PABA free, and water-soluble. They combine protection from multiple forms of ultraviolet radiation (UVR) with protection from cellular oxidation reactions and even atmospheric environmental damage. They also offer total protection for continuous use, either as an elegant cover-up liquid make-up or a clear version. Tinted SPF 60 and Clear SPF 65 incorporate eight forms of mill-dispersed solids, ranging in controlled particle-size from 10 microns down to a few nanometers. These particles are

IX. FALLENE LTD. & FULL SPECTRUM SUN PROECTION

IX. Fallene Ltd. & Full Spectrum Sun Protection

59

suspended homogeneously to achieve maximum protection throughout the entire UVB/UVA range. Micro-dispersed particles shield the skin from atmospheric damage and trauma. Eight forms of micronized and sub-micronized particles of titanium dioxide, sub-micronized zinc oxide, along with ultra-micronized iron oxide form the foundation for a wall of reflection and refraction.

Tinted/Cover-Up SPF 60 and Clear SPF 65 contain:

Three soluble organic non-PABA sunscreen UV absorbers to assure continuous uninterrupted UVB absorption coverage

Elefac® I-205, a proven, patented UV protection factor booster, plus two special polymeric materials that enhance both the UV protection factor and strengthen its atmospheric skin–shield effectiveness.

Six antioxidants/trace element additives that both augment the lotion’s UV protection activity and reduce acute oxidation damage to skin cells

A series of antioxidant free-radical scavengers that provide direct cellular protection via the addition of Tocopherol and Tocopheryl acetate (two forms of vitamin E), which are recognized antioxidants, and effective topical cellular protectants. Pycnogenol® (Maritime Pine extract), reported to be one of the most potent free-radical inhibitors, a vitamin C derivative, and Beta-Carotene, are also solubilized into these lotions.

Selenium protein complex: Topical application of organic selenium complexes have been demonstrated to increase Minimal Erythema Dose response (MED) while reducing acute skin cell damage due to UV exposure.

Ultra-micronized iron oxide (unique to our products), which acts as a radiation protectant by absorbing and scattering all wavelengths of electromagnetic radiation (UV, visible and infrared)

Physical Blockers in Tinted/Cover-Up SPF 60 and Clear SPF 65

Two forms of titanium dioxide were selected for these products. First is an opaque, cosmetic form that reflects and scatters most wavelengths of UVB plus some UVA. Second is sub-micronized “transparent” titanium dioxide. This form of titanium dioxide allows for a much higher percentage of protection while retaining cosmetic elegance, and achieving an increase in UVB protection. Together, these two titanium dioxides (differing only in particle size) obtain excellent UVB protection (High SPF) plus moderate UVA protection.


60

Zinc OxideSupplementing the opaque and “transparent” titanium dioxides is “transparent” sub-micron zinc oxide (Z-Cote ®). Its protective abilities cover UVB and a majority of UVA radiation.Zinc Oxide has been used topically for centuries as a skin protectant and wound healing adjuvant. It is a recognized mild antimicrobial agent. It also reflects infrared from the skin, as does titanium dioxide, however, its ability to protect in the long UVA range is much higher than titanium dioxide. Ultra-fine zinc oxide “closes the window” in the UVA range left open by titanium dioxide. Zinc oxide works to both complement titanium dioxide’s protection and extend photoprotection to the skin where titanium dioxide is insufficient.

Iron OxidesThese cosmetic pigments not only add color to the lotion, but also contribute significant protection of the skin from all “light” forms (UVC, UVB, UVA, Visible).

Indirect Physical Blockers To boost the effectiveness of the various “oxide” particles, special ultra–flat particles are incorporated. They are very small, pleasant feeling particles but much larger than direct physical blockers. These overlapping particles increase protection on the skin.

PolymersPolymers are the skin protective compounds that assure all of the “light” protective materials bond to the skin surface in a multi-layer film, giving increased and uniform overall protection. The lotion’s myriad of “light” absorbers and blockers are further enhanced by still another unique material, caramel. Emolliency is extended by a patented SPF (UVB) booster, Elefac®I – 205 [octyldodecyl neopentanoate].

Tinted SPF 60

Tinted SPF 60 make-up is the only individually customizable, liquid make-up foundation that can be color adjusted to match almost any skin tone while completely protecting the skin from the damaging UVB/UVA rays. It is packaged with Light and Dark color concentrates, allowing each person to adjust the product’s base color to closely match his or her skin tone. The Light Color Concentrate contains titanium dioxide powder with glycols that allow it to mix into a liquid form. The Dark Color Concentrate contains iron oxide powder with glycols that allow it to mix into a liquid form. These dark and light color control adjustors are included with each package of Tinted SPF 60.

Tinted SPF 60 may be used as a foundation make-up or a camouflage cover-up for skin imperfections such as melasma, vitiligo, post-laser surgery, post skin cancer removal,


61

hyperpigmentation, discoid Lupus or any condition where the skin requires camouflage make-up, including rosacea. SPF 58

SPF 58 is mineral based, utilizing ultra-micronized titanium dioxide and zinc oxide as its approved active sunscreen ingredients. It is free of dyes, fragrance and is “chemical sunscreen free” (some individuals experience skin sensitivity due to chemical sunscreen filters). It is excellent for pediatric use as well as for those with sensitive skin. It offers significant water resistant properties making it ideal for all outdoor activities. SPF 58 sunscreen is elegant and highly protective for daily use, leaving the skin soft, smooth and UVA/UVB protected. It is oil, PABA and fragrance free.

SPF 40, Facial Mineral Fusion

The SPF 40 is formulated with multiple physical particle sizes of micronized titanium and zinc, yet dries to a clear, matte finish on any complexion. This unique formulation offers unparalleled protection, practically undetectable defense for the face that truly feels like silk on your skin. The SPF 40 is paraben, oil and fragrance free and is specially formulated without UV absorbing chemicals to offer superior, irritant free UVA/UVB light protection.

No other sunscreen compares to the SPF 40’s protective capability. It is an everyday necessity and not just a summer beach product. SPF 40 was specifically designed for individuals concerned with blocking the complete light spectrum. Each formulation offers unparalleled protection for the medically photosensitive individual, and those concerned about the damaging effects of the sun.

Titanium, Iron, & Zinc Oxide • Elegant and silky, yet leaves a matte finish• Titanium, Zinc, and Iron Oxide for mineral protection • Physical protection that matches all skin tones and types • Very water and sweat resistant, up to 80 minutes• Excellent for sensitive skin• NO chemical sunscreen filters• NO parabens, dyes, fragrances, oils or PABA• Complete full spectrum UVB/UVA Protection


62

Fallene Introduces our NEW SPF 35 for ultra sensitive skin — 20% Zinc Oxide.

Utilizing multiple particle sizes of 20% Zinc Oxide dispersion, this single sunscreen filter, the SPF 35 offers a soft, silky elegant feel that dries clear, while providing superb photo protection. TiZO Body is water resistant, Paraben, fragrance and free of chemical sunscreens.

SPF 45 Lip Protection

SPF45 lip protection combines multiple particle sizes of titanium dioxide, zinc oxide and iron oxide to offer excellent “chemical sunscreen free,” full spectrum protection. This product is ideal for photosensitive patients who need complete full spectrum protection in an elegant and soothing formula that fades to a natural tone.


63

X. COMMONLY ASKED QUESTIONS

SUNSCREEN

. Are some sunscreen ingredients more effective than others?Yes, Titanium Dioxide and Zinc Oxide. Titanium dioxide and zinc oxide are physical blocks; they provide protection by sitting on the skin and reflecting and refracting light. (In contrast, chemical blocks are absorbed into the skin where they, in turn, absorb portions of the light spectrum.) These physical blocks protect against a broad range of UVA and UVB light, are not harmful to the skin and are more effective relative to chemical sunscreen filters, which can break down in the sun.

. Do I need full-spectrum protection?Absolutely. While UVB rays are known to cause sunburn and skin cancer, they do not penetrate the skin as deeply as UVA rays. UVA rays have been proven to cause skin cancer and skin aging. It is important to choose a sunscreen that protects against a wide range of ultraviolet light.

. Will sunscreen shield me from all the sun’s rays?It depends upon the product. Check the label to make sure it blocks both UVA and UVB radiation. For best results, look for titanium dioxide and zinc oxide in the list of active ingredients.

SUNBURN

. What is a sunburn?Sunburn is inflammation of the skin caused by overexposure to ultraviolet (UVB) radiation from the sun. A similar burn can follow overexposure to a “sun” (tanning) lamp. UV radiation can also damage the eyes, although no surface burn is apparent.

. Can sunburn cause permanent damage?Yes. Sunburn early in life increases the risk of developing skin cancer later. Repeated overexposure to ultraviolet rays can also scar, freckle, dry out, and/or prematurely wrinkle the skin. In addition, frequent overexposure to ultraviolet rays can increase the risk of developing eye cataracts and macular degeneration, a leading cause of blindness.

. What are the symptoms of sunburn?Initially, the skin becomes red, tender and hot. Touching or rubbing it is causes pain. Because heat triggers fluid loss, a sunburn victim can also become dehydrated. For several days after exposure, the skin may swell, blister, and peel. Some sufferers develop welts or rashes. The symptoms of sunburn can be mild, moderate or severe, depending mainly on the following:

1. Skin type2. Time, length, location, and altitude of exposure


64

3. Medications victim has been taking4. Skin preparations victim has been using

In severe cases of sunburn, the victim may experience fever, nausea, chills, dizziness, rapid pulse, rapid breathing, shock, and loss of consciousness. When present, these symptoms require emergency treatment.

. Who is most susceptible to sunburn?Persons with certain pigment disorders (such as albinism) and persons with fair skin are at highest risk of suffering a burn. The American Academy of Dermatology classifies skin types into six categories (in terms of susceptibility to sunburn) for skin colors ranging from fair to black. These skin types are as follows:

Types1and2:HighSusceptibilitytoSunburnPersons with Skin Type 1 have very fair skin (pale or milky white), blond or red hair, and possibly freckles. They can suffer a burn in less than half an hour when exposed to summer sunlight at midday. They never tan.

Persons with Skin Type 2 have very light brown skin and possibly freckles. They burn in a short time in the sun, although they can achieve a very light tan.

Types3and4:ModerateSusceptibilitytoSunburnPersons with Skin Type 3 (called “Average Caucasians”) by The American Academy of Dermatology) have skin that is slightly browner than the skin of Type 2. They can develop moderate sunburn and a light brown tan.

Persons with Skin Type 4 have olive-colored skin. Ordinarily, they develop only minor sunburn while acquiring a moderate tan.

Types5and6:MinimalorNoSusceptibilitytoSunburnPersons with Skin Type 5 have brown skin and can develop a dark tan while rarely burning.

Persons with Skin Type 6 have black skin and never burn.

. How can I tan without burning?There is no such thing as a “safe” tan. Chronic exposure to the sun causes long-term problems including cancer. One in five Americans will develop skin cancer in their lifetime as a result of too much sun exposure. Some people believe that indoor tanning is a safer alternative to the sun, however, recent study reveals that users of indoor tanning devices actually have a higher risk of developing melanoma than non-users.

. How can sunburn and skin cancer be prevented?The ideal methods of preventing sunburn, and hopefully skin cancer, involve:

1. Limiting the amount of sun exposure and avoiding it when the sun’s rays are strongest, from late morning to early mid-day;

2. Wearing protective clothing such as a broad-brimmed hat, long-legged pants, and shirts


65

with sleeves that cover the arms;

3. Being aware that sunburn can occur even on a cloudy day (clouds don’t stop the ultraviolet rays) and even when you are in the water;

4. Remembering that sand and other surfaces reflect sun rays and increase the chance of burning;

5. Using a protective sunscreen to minimize the penetration of UV rays. Sunscreens with a Skin Protection Factor (SPF) of at least 30 are recommended for most people. This should be applied thirty minutes before going into the sun and reapplied often

SKIN CANCER

. What kinds of cancer can UV rays cause?Overexposure to UV rays can cause three varieties of skin cancer; malignant melanoma, basal cell carcinoma, and squamous cell carcinoma.

Malignant melanoma is by far the most dangerous form of skin cancer. This form of cancer usually begins from a mole. The border of the mole assumes an irregular shape. The mole is black or brown – and sometimes red, white or blue, or a mixture of those colors. Melanoma can spread (metastasize) rapidly. Diagnosed early, melanoma is curable. Diagnosed late, melanoma is likely to kill.

Basal and squamous cell cancers are slow-growing and are far less likely to metastasize than melanoma. If diagnosed early, both basal and squamous cell cancers can be cured in at least 90 percent of cases.

Basal cell carcinomas are flat, pearly patches with translucent edges and dimpled centers. They may bleed. Usually, they appear on the head, neck, upper trunk, and hands. If ignored, these cancers can cause considerable localized damage.

Squamous cell carcinomas are rough patches or crusty scaly areas on the skin that do not clear up and do not respond to the usual skin creams. They may bleed a little. They tend to appear particularly on the ear rims, face, lower lip, and hands. If ignored, they can spread to other parts of the body.

. What do we know about skin cancer today that we didn’t know a year ago?

For the first time, the death rate from melanoma has stabilized and may even be falling. The incidence rate of melanoma seems to be stabilizing as well.

. Will there be a vaccine for melanoma? Who will be eligible to get it?

There are a number of experimental vaccines in varying types of trials. To date, none has proven successful in the long-term treatment of advanced melanoma.


66

. Are all melanomas pigmented?No. A small percentage of melanomas are non-pigmented, also known as amelanotic.

. Is melanoma definitely linked to sun exposure?While the linkage has not proven been proven as it has with squamous cell carcinoma, there is no question that melanoma is related, at least in part, to sun exposure.

. What is the best way to protect against melanoma?Sun protection in the form of full-spectrum sunscreens, wearing protective clothing during sun exposure, and time of day during which exposure takes place all factor into helping protect against melanoma and all skin cancers. Try to avoid long periods of time in the sun, along with avoiding sun exposure as much as possible between the hours of 10 a.m. and 4 p.m.

. Has there been an increase in the past decade of other types of skin cancer, such as basal cell and squamous cell?

Yes. Cases of both basal cell and squamous cell carcinoma have substantially increased.

. Should everyone, regardless of whether they have ever had any kind of skin cancer, have a body check yearly?

Obviously those individuals with the greatest number of risk factors (past history of skin cancer, atypical nevi, those who are fair-skinned, freckled, have light eyes, family history of skin cancer, etc.) should definitely be screened at least annually. Some high-risk individuals should be seen more frequently.

. Are there any typical sites where these skin cancers occur? Do they vary by gender?

Sun exposed areas are at greatest risk: the trunk, extremities, head, and neck. Interestingly, for women, the trunk of the body and legs are the sites most common for skin cancers. In men, it is most often the trunk.

. Do melanomas affect a certain population or demographic more than others?

Generally, people with fair skin, light eyes and a tendency to burn rather than tan are most susceptible. The Celtic, Nordic and Germanic populations tend to be more susceptible than darker-skinned individuals. A family history in all races plays an important role.

. At what age do actinic keratoses begin to appear?These precancerous spots often appear between 40 and 50 years of age; in some fair complexioned people they appear even earlier. The key aspects that differentiate them from the brown spots caused by photodamage are that they are pink-brown and often scaly. Spots fitting this description should be brought to the attention of a dermatologist.


67

THE LIGHT SPECTRUM

. What is Ultraviolet (UV) light?UV light is radiation energy in the form of invisible light waves. UV light is emitted by both the sun and by tanning lamps.

The sun discharges three types of ultraviolet radiation: ultraviolet A (UVA), ultraviolet B (UVB), and ultraviolet C (UVC). Only UVA and UVB reach the earth. (UVC does not penetrate the earth’s upper atmosphere.) Although research has long implicated UVB as the most likely form of UV to damage the skin and cause skin cancer, recent studies suggest that UVA is also dangerous.

Tanning lamps also produce UVA and /or UVB. These artificial rays affect the skin in the same way as UVA and UVB from the sun.

. When and where are UV rays most intense?UVB rays are most intense at noon and the hours immediately before and after (between 10 a.m. and 3 p.m.), particularly in the late spring, summer and early autumn. Although they are less concentrated at other times of the day and year, UVB & UVA can still damage the skin and eyes even in the dead of winter. UVA rays stay the same, all day, every day, all year long.

UVB rays also increase in intensity in relation to altitude and latitude. The higher the altitude, the greater is the concentration of UVB rays. Likewise, the rays are more powerful the nearer the latitude to the equator.

UV rays “bounce” off reflective surfaces – including water, sand, and snow. Thus a skier, swimmer, fisherman, or beachcomber may be bombarded with UV rays from above and below. Many an outdoors lover who skipped sunscreen has learned this lesson the hard way.

. Why does the skin tan after exposure to UV rays?The skin contains a pigment called melanin that colors the skin and creates the variety of skin tones we all recognize. Melanin blocks at least some of UV rays from penetrating the skin. After repeated or prolonged exposure to UV rays, the skin produces more melanin. Consequently, the skin darkens or tans, which in turn protects the skin.

PHOTOSENSITIVITY

. Can diseases cause a heightened sensitivity to UV rays?Yes. Certain disorders place the people who suffer from them at very high risk of skin damage – including severe sunburn, blisters, and sores – from exposure to UV radiation.


68

The following is a small sample of diseases that increase the skin’s sensitivity to UV radiation:

• Albinism: Persons with classic oculocutaneous albinism lack melanin in their skin and eyes – hence, the term “oculocutaneous” (“oculo” for eyes, and “cutaneous” for skin). Without the protection of this pigment, their white skin and pink eyes are both highly sensitive to UV and susceptible to the rays’ damage.

• Porphyrias: The porphyries are disorders of specific enzymes that are needed for the metabolism of heme (part of the pigment hemoglobin that permits red blood cells to transport oxygen and carbon dioxide). Patients with these disorders manufacture abnormally large amounts of substances called porphyrins. Stimulation of the excess porphyrins in the skin by the UV rays causes damage and scarring of the skin. This skin damage is a prominent feature of several forms of porphyria including porphyria cutanea tarda, hereditary coproporphyria, variegate porphyria, and particularly, congenital erythropoietic porphyria.

• Vitiligo: Vitiligo is a relatively common disorder that causes patches of white depigmented skin. These patches lack melanin and are extremely sensitive to UV rays.

• Xerodermapigmentosum: This disorder appears to result from an inherited hypersensitivity to the cancer-causing (carcinogenic) effects of ultraviolet light. Sunlight causes DNA damage that is normally repaired. Persons with this condition have defective inability to repair the DNA after UV damage. Affected individuals are a hundred times more vulnerable to developing skin cancer than other people. Their extreme skin photosensitivity predisposes them to pronounced skin damage and scarring but also to the early onset of skin cancer (basal cell and squamous cell carcinomas and malignant melanoma).

. What are sun-sensitizing drugs?Sun-sensitizing drugs are medications that can increase the skin’s susceptibility to reddening and burning from the sun (or a tanning lamp). These drugs are also called photosensitizing agents.

It is very important to read the label carefully before using a prescription or non-prescription medication, paying particular attention to side effects such as photosensitivity. (For a partial reference list of sun-sensitizing drugs, see Appendix B).

. What medications and products can increase the skin’s sensitivity to the sun?

Many prescription and non-prescription drugs contain photosensitizing agents that can cause sunburn, blistering, hives, rash or other skin reactions. These reactions are classified as either photoallergic or phototoxic. (For a partial reference list of photo-sensitizing drugs, see Appendix B).


69

. What is the difference between a photoallergic and a phototoxic reaction?

In a photoallergic reaction, a drug or an ingredient in a drug combines with ultraviolet light to produce a mixture that the immune system mistakenly perceives as a harmful invader, or antigen. Even though the mixture poses no threat and causes no symptoms, the misinformed immune system produces antibodies (proteins that fight and eliminate antigens) to repel future invasions of the mixture. When the photosensitizing drug is taken again, the antibodies wildly attack the harmless invader and end up damaging the body in the process.

In a phototoxic reaction, a response from the immune system does not occur. Instead, the skin reacts as if poisoned, generally exhibiting symptoms shortly after the drug is taken the first time.

Among agents that can cause a photoallergic or phototoxic reaction are sulfa drugs, known as sulfonamides, and some antibiotics. Other agents that can cause sun sensitivity include some antidepressants (including tricyclic drugs and the presently popular herbal remedy St. John’s Wort); tranquilizers; birth-control pills; arthritis painkillers; oral diabetes medications; and drugs to treat allergies, cancer, colds, high blood pressure, and heart rhythm problems. In addition, certain creams, lotions and other skin preparations for acne and other conditions can cause photosensitivity.

FREE RADICALS AND ANTIOXIDANTS

. What are free radicals? Free radicals are highly reactive molecules that attack cells and damage collagen and elastin. They are triggered by pollution, sun, stress, smoke, oxygen, even the body’s own processes. Free radicals are believed to be partly responsible for aging skin through a process called oxidation. A free radical, known as Reactive Oxygen Species, attacks another molecule and steals an electron from it, setting off a chain reaction of free radical damage to cells. Photons may collide with vulnerable electrons of atoms in cellular structures, creating free radical chain reactions that may overwhelm the natural antioxidant structures, consequently leading to the destruction of vitamin A, C, E and other molecules.

. What is an antioxidant?An antioxidant is a molecule that helps neutralize free radicals and protects skin by helping to block damaging reactions to skin cells. Vitamin A reduces the number of sunburn cells after UV radiation. If the skin is rich in antioxidants then the levels of vitamin A remain normal and the network antioxidants (vitamins C & E, co-enzyme Q10, alpha lipoic acid and glutathione) recycle each other back into activity. The ideal sunscreen should contain antioxidants.


70

FALLENE PRODUCTS

. What makes Fallene sunscreens so effective?Fallene lotions are so effective because they are formulated with a multitude of ingredients to protect against all forms of light, especially UVA/UVB, and their harmful effects. Our products utilize nanoparticle technology in the form of eight dispersed, highly reflective particles, ranging in size from 10 microns down to a few nanometers (a billionth of a meter or 3,000 particles to cover the cross section of a hair). These particles form a wall of reflection. In addition, there are three soluble organic chemical sunscreen absorbers (non-PABA) to assure continuous protection. Protective capabilities are enhanced by six antioxidants and trace elements, vitamin C, two forms of vitamin E, along with Maritime Pine extract (Pycnogenol®), all designed to counteract free-radical damage and increase protection from ultraviolet and acute oxidation damage. Also among these protective ingredients are organic selenium protein complex, which has been demonstrated to reduce acute skin cell damage due to ultraviolet exposure, and Elefac® I-205, which gives a proven, patented, ultraviolet protection factor boost and strengthens atmospheric skin-shield effectiveness.

Does SPF 65 dry clear?Yes, on most skin tones.

Does SPF 58 dry Clear? Yes, on most skin tones.

How do I customize the tinted SPF 60 for my skin? About 50% of the population can use the product as packaged without adding any tint. If you need to, just add 6 to 10 drops of either the light or dark color pack. After adding, shake the bottle to mix thoroughly. Continue until desired color is achieved.

What is the difference between the SPF 65 and SPF 58?SPF 65 contains three organic chemicals and is non-comedogenic. SPF 58 contains NO chemical sunscreen filters and is heat and water-resistant. It is highly recommended for children and those with sensitive skin.

What percentage of oxides are contained in each product?

Oxide SPF58 SPF65Clear SPF60 LipBalm SPF35 SPF40Titanium dioxide 10.0 4.0 10.0 4.0 0.0 8.0Zinc oxide 3.0 5.0 3.4 5.5 20.0 3.8Iron oxide 0.4 0.3 0.9 0.4 0.0 0.0


71

The Facts of Light VI: Myth Busting

False True

A sun tan is healthy. A tan results from your body defending itself against further damage from UV radiation.

A tan protects you from the sun. A dark tan on white skin only offers an SPF of about 4.

You can’t get sunburned on a cloudy day.

Up to 80% of solar UV radiation can penetrate light cloud cover. Haze in the atmosphere can even increase UV radiation exposure.

UV radiation during the winter is not dangerous.

UVB radiation is generally lower during the winter months, but snow reflection can double your overall exposure, especially at high altitude. UVA radiation is the same all year round.

Sunscreens protect you so you can sunbathe much longer.

Sunscreens are not intended to increase sun exposure time, but to increase protection during unavoidable exposure. The protection they afford is critically dependent on their correct application.

If you take regular breaks during sunbathing, you won’t get sunburned.

UV radiation is cumulative during the day.

If you don’t feel the hot rays of the sun, you won’t get burned.

Sunburn is caused by UVB radiation, which cannot be felt. Most of the heating is caused by the sun’s visible and infrared radiation and not by UV radiation.

You can’t get sunburned while in the water

Water offers only minimal protection from UV radiation, and reflections from water can enhance your UV radiation exposure.


72

APPENDIX A:

How SPF is Determined by OTC Monograph Testing

Testing labs determine the Sun Protection Factor (SPF) value of a sunscreen product for efficacy and labeling purposes by following a procedure based on the method outlined in the Food and Drug Administration (FDA) Final Monograph for sunscreen testing published in the Federal Register, Vol. 64, No. 98, May 21, 1999.

Inclusion Criteria:1. At least twenty (20) but not more than twenty-five (25) healthy male or female volunteers

of skin types I – III as described below:A. Always burns easily; never tans (sensitive)B. Always burns easily; tans minimally (sensitive)C. Burns moderately; tans gradually (light brown) (normal)D. Burns minimally; always tans well (moderate brown)E. Rarely burns; tans profusely (dark brown)(insensitive)F. Never burns; deeply pigmented (insensitive)

2. Ages 18-65 years old.3. Absence of any visible skin disease which might be confused with a skin reaction from the

Test Material4. Completion of a Medical History Form and the understanding and signing of a legally

effective Informed Consent form5. Considered dependable and capable of following directions

Exclusion Criteria:1. Subjects with a history of abnormal response to sunlight or those taking medication which

might produce an abnormal response to sunlight2. Subjects exhibiting current sunburn, suntan, or uneven skin tone or visible skin disease

which might interfere with evaluation of test results3. Presence of nevi, blemishes, or moles that, in the Investigator’s judgment, would interfere

with the study results. Excess hair on the back would be accepted if hair is clipped or shaved

4. Subjects with a history of lupus, erythematosis, or skin cancer5. Females who are pregnant or lactating

Test Method:Twenty-Five (25) subjects who meet the inclusion criteria are selected for participation.

LightSource - A Xenon Arc Solar Simulator (150w) can be used as the source of ultraviolet light irradiation (Such as the product sold by Solar Light Company, Philadelphia, PA). This instrument, described in detail in J. Invest. Dermatol. 53, 192 (1969), provides a pectoral output in the ultraviolet range comparable to that of natural sunlight. The specific filters can be used to provide a basis UV-A and UV-B wavelength spectrum, with wavelength ranges of 290-400 nm.

Appendix A

73

The lamp output can be measured with the UV intensity meter (Model PMA2100, Solar Light Company, Philadelphia, PA) before and after the test period.

DeterminationofMinimalErythemalDose(MED) - An MED is defined as the lowest time interval or dosage of UV light irradiation sufficient to produce defined erythema on designated test sites. Prior to the product testing phase, the MED of the unprotected skin of each subject was determined by a progressive sequence of timed UV light exposures, graduated incrementally by 25% over that of the previous exposure. The sites were evaluated for erythema according to the following scoring system:

0 No reaction0.5 Equivocal reaction, barely perceptible erythema with no clearly defined border1 Mild but definite erythema with clearly defined border2 Moderate clearly defined erythema3 Strong erythema (redness), edema (swelling)4 Bulla or vesiculation (blistering)

DeterminationofStaticSPFValues – A sufficient number of 50 square centimeter test site areas should be outlined with surgical marking pen on the subject’s back between the scapulae and the beltline, lateral to the midline. These areas are designated for applications of the Test Material and Standard, with an adjacent site designated for a concurrent MED determination (unprotected control).

A 2 mg/cm² portion of the Test Material and of the Standard can be applied to the appropriate designated test site and spread evenly over the site using a fingercot. After product application, each test area can be subdivided into sites that are used for defined serial UV light exposures. Irradiation of the sites is begun no less than 15 minutes after application.

Exposure times were selected for each site in treated areas based upon the previously determined MED of unprotected skin and the expected SPF of the Test Material and HMS Standard. After irradiation was completed for each area, responses for tanning, reddening, and heat response were recorded as absent (0) or present (1).

EvaluationofTestSites– All test sites are evaluated 22 to 24 hours after irradiation to determine minimal erythemal response of all sites. The MED evaluator did not apply or irradiate the test material.

Control Material:Concurrent with the evaluation of the test material, a standard sunscreen preparation of 8% Homosalate with mean SPF value of 4.47 ± 1.28 was tested.

Appendix A

74

Statistical Methodology:

SPFDetermination- The SPF is defined as the ratio of the amount of energy or time required to produce an MED on protected skin (treated with Test Material(s) or Standard) to the amount of energy or time needed to produce an MED on untreated skin and is calculated as follows:

The final Label SPF for the test material is calculated as follows:

Calculation of A:

Where n = number of subjects; t = upper 5% point from the t distribution with n-1 degree of freedom; and s = standard deviation.

SPFLabel=largestwholenumberlessthanx–AWhere x is the mean SPF value.

Appendix A

SPF = MEDTest_MaterialMEDControl

= (t)(s)n√

75

APPENDIX B:

Prescription Drugs and Photosensitivity

Four hundred drugs are known to cause photosensitive and photoallergic reactions. The list includes certain antibiotics, birth control pills, diuretics, antihistamines, antidepressants and many retinoids (such as vitamin A acid).

Commonly Prescribed Drugs That Can Cause Photosensitivity:

A. Drugs known to cause photoallergic, photo recall, photosensitive and phototoxic reactions *

PHOTOALLERGICREACTIONBimatoprostCelecoxibChlorothiazideDiclofenacEnoxacinEstrogensFenofibrateHydrochlorothiazide

IbuprofenImipramineIndomethacinItraconazoleMethoxsalenNalidixic AcidPentobarbitalPhenobarbital

PiroxicamPromazinePromethazinePsoralensPyrazinamideQuinethazoneQuinidineQuinine

PHOTORECALL

Appendix B

StatinsSulfa Drugs

ACE InhibitorsAntiarrythmic AgentsAnti-DepressantsBirth Control PillsCalcium Channel Blockers

Chemotherapy AgentsCorticosteroids Hydrochlorothiazide Immunosuppressive AgentsInterferon

NSAID’s PremarinQuinilones Retin A®SSRI’s

SulfisoxazoleThimerosalThioridazineTolbutamideTrioxsalenVancomycin

AcyclovirAmpicillinAspirinBleomycinBuspironeCapecitabineCefazolinCiprofloxacinCo-Trimoxazole

CodeineCyclophosphamideDactinomycinDocetaxelDoxorubicinEpirubicinEtoposideFluorouracilGemcitabine

HaloperidolHydroxyureaIdarubicinInterferons, Alfa-2MercaptopurineMethotrexateMitomycinOxaliplatinPaclitaxel

PiperacillinSimvastatinSulfamethoxazoleTamoxifenTobramycinVinblastine

76

AcamprosateAcetaminophenAcetazolamideAcetohexamideAcyclovirAldesleukinAlitretinoinAllopurinolAlmotriptanAlprazolamAmantadineAmilorideAminolevulinic AcidAminosalicylate SodiumAmiodaroneAmitriptylineAmobarbitalAmoxapineAnagrelideAnthrax VaccineArsenicAtazanavirAtenololAtorvastatinAtropine SulfateAzatadineAzathioprineAzithromycinBenazeprilBendroflumethiazideBenzthiazideBenztropineBergamotBetaxololBexaroteneBimatoprostBisoprololBrompheniramineBumetanideBupropionButabarbitalButalbitalCapecitabineCaptoprilCarbamazepine

CarisoprodolCarteololCarvedilolCefazolinCeftazidimeCelecoxibCetirizineCevimelineChlorambucilChlordiazepoxideChlorhexidineChloroquineChlorothiazideChlorotrianiseneChlorpheniramineChlorpromazineChlorpropamideChlortetracyclineChlorthalidoneCinoxacinCiprofloxacinCitalopramClemastineClofazimineClofibrateClomipramineClopidogrelClorazepateClozapineCo-TrimoxazoleColchicineCorticosteroidsCromolynCyclamateCyclobenzaprineCyclothiazideCyproheptadineDacarbazineDanazolDantroleneDapsoneDemeclocyclineDesipramineDexchlorpheniramineDiazoxide

DiclofenacDiflunisalDiltiazemDimenhydrinateDiphenhydramineDisopyramideDocetaxelDong QuaiDoxepinDoxycyclineDuloxetineEfavirenzEnalaprilEnoxacinEpirubicinEpoetin AlfaEsomeprazoleEstazolamEstrogensEthacrynic AcidEthambutolEthionamideEtodolacFelbamateFenofibrateFloxuridineFlucytosineFluorouracilFluoxetineFluphenazineFlurbiprofenFlutamideFluvastatinFluvoxamineFosinoprilFurazolidoneFurosemideGanciclovirGatifloxacinGemifloxacinGentamicinGlatiramerGlimepirideGlipizideGlyburide

GlycopyrrolateGold And Gold CompoundsGoldensealGrepafloxacinGriseofulvinHaloperidolHennaHeroinHydralazineHydrochlorothiazideHydroflumethiazideHydroxychloroquineHydroxyureaHydroxyzineHyoscyamineIbuprofenImatinibImipramineIndapamideIndomethacinInfliximabInterferon Beta 1-AInterferon Beta-1bInterferons, Alfa-2IrinotecanIsocarboxazidIsoniazidIsotretinoinItraconazoleKanamycinKavaKetoconazoleKetoprofenKetotifenLamotrigineLeuprolideLevofloxacinLincomycinLisinoprilLomefloxacinLoratadineLosartanLoxapineMaprotilineMeclizine

Appendix B

PHOTOSENSITIVITY

77

MeclofenamateMedroxyprogesteroneMefenamic AcidMelatoninMeloxicamMeprobamateMercaptopurineMesalamineMesoridazineMetforminMethazolamideMethenamineMethotrexateMethoxsalenMethyclothiazideMethyldopaMethylphenidateMetolazoneMinocyclineMirtazapineMitomycinMoexiprilMolindoneMoxifloxacinNabumetoneNalidixic AcidNaproxenNaproxenNaratriptanNefazodoneNifedipineNisoldipineNitrofurantoinNorfloxacinNortriptylineOfloxacinOlanzapineOral ContraceptivesOxaprozinOxcarbazepineOxytetracyclinePaclitaxelPantoprazoleParoxetinePentobarbital

PentosanPentostatinPerphenazinePhenelzinePhenindaminePhenobarbitalPilocarpinePimozidePiroxicamPolythiazidePravastatinProcarbazineProchlorperazineProcyclidinePromazinePromethazinePropranololPropylthiouracilProtriptylinePsoralensPyrazinamidePyridoxinePyrilaminePyrimethamineQuetiapineQuinacrineQuinaprilQuinestrolQuinethazoneQuinidineQuinineRabeprazoleRamiprilRanitidineRibavirinRiluzoleRisperidoneRitonavirRofecoxibRopiniroleRueSaccharinSaquinavirScopolamineSelegiline

SeleniumSertralineSildenafilSimvastatinSmallpox VaccineSotalolSparfloxacinSpironolactoneSt John’s WortStreptomycinSulfacetamideSulfadiazineSulfadoxineSulfamethoxazoleSulfasalazineSulfisoxazoleSulindacSumatriptanTacrolimusTartrazineTerbinafineTetracyclineThimerosalThioguanineThioridazineThiothixeneTiagabineTimololTioproninTolazamideTolbutamideTolmetinTopiramateTorsemideTranylcypromineTrazodoneTretinoinTriamtereneTriazolamTrichlormethiazideTrifluoperazineTrihexyphenidylTrimeprazineTrimethadioneTrimethoprim

TrimetrexateTrimipramineTrioxsalenTripelennamineTriprolidineTrovafloxacinValdecoxibValproic AcidValsartanVancomycinVardenafilVenlafaxineVerapamilVerteporfinVinblastineVitamin AVoriconazoleYarrowZalcitabineZaleplonZiprasidoneZolmitriptanZolpidem

PHOTOSENSITIVITY (Continued)

Appendix B

78

AcitretinAlprazolamBendroflumethiazideBergamotCaptoprilCetirizineChlorpromazineCiprofloxacinClarithromycinDemeclocyclineDong QuaiDoxycyclineEnoxacin

FenofibrateFluorouracilFluoxetineFurosemideGlipizideGoldensealGrepafloxacinHydrochlorothiazideHydroxychloroquineItraconazoleLevofloxacinLomefloxacinMethoxsalen

MinocyclineNabumetoneNaproxenNorfloxacinNortriptylineOfloxacinOxaprozinPantoprazoleProchlorperazinePromazinePropranololProtriptylinePsoralens

RofecoxibSparfloxacinSulfisoxazoleSulindacTerazosinTetracyclineThioridazineTrioxsalenTrovafloxacinVinblasti

PHOTOTOXICREACTION

Appendix B

B. Examples of Classes of Photosensitizing Drugs

AIDSANTIRETROVIRALRitonavir (Novir®)Saquinavir (Invirase®, Fortovase®)Somatropin (*Serostim®)

ANTIARRHYTHMICAmiodarone (*Cordarone®, *Pacerone®)

ANTIARTHRITIC/ANALGESICCelecoxib (Celebrex®)Diclofenac (Voltaren®)Etodolacn (Lodine)Ibuprofen (Motrin®)Ketoprofen (Orudis®, Oruvail®)Meloxicam (Mobic®)Naproxen (Naprosyn®, EC-Naprosyn®,*Naprelan®)Nabumetone (Relafen®)Naproxen Sodium (Anaprox®)Oxycodone (Roxicodone®)Sulindac (Clinoril®)Sumatripan (Imitrex®)

ANTIBIOTIC/ANTIMICROBIAL/ANTIVIRALAcyclovir (Zovirax®)Azithromycin (Zithromax®)Cidofovir (Vistide®)Ciprofloxacine (Cipro®)Clindamycin (Clindagel™)

Demeclocycline (Declomycin®)Doxycycline (Doryx®, monodox®,Vibramycin®, Vibra-Tabs®)Griseofulvin (Grifulvin V®)Norfloxacin (Floxin®)Pentosan (Elmiron®)Sulfamethoxazole-Trimethoprim(Bactrim®,Septra®)Sulfisoxazole-Erythromycin (Pediazole®)Trovafloxacin Mesylate (Trovan®)Valacyclovir (Valtrex®)

ANTICONVULSANTDivalproex (Depakote®)Valproate (Depacon®)Valproic Acid (Depakene®)

ANTIDEPRESSANTAmitriptyline (Etrafon®, Limbitrol®)Desipramine (Norpramin®)Protriptyline (Vivactil®)Trimipramine (Surmontil®)

79

ANTIEPILEPTICOxcarbazepine (Trileptal®)

ANTIFUNGALFlucytosine (Ancobon®)

ANTIHISTAMINICCetrizine Hydrochloride (Zyrtec®)Cyprohepyide (Periactin®)Diphenhydramine (Benadryl®, Parenteral)

ANTIHYPERTENSIVEAtenolol-Chlorthalidone (T enoretic®)Benazepril (Lotensin®)Bisoprolol-Hydrochlorothiazide (Ziac®)Clonidine-Chlorthalidone (Clorpres™, Combipres®)Diltiazem (Tiazac®, Cardizem®)Enalapril (Vasotec®)Enalapril-Felodipine (Lexxel®)Enalapril-Hydrochlorothiazide (Vaseretic®)Fosinopril (Monopril®)Hydrochlorothiazide (Microzide®)Losartan (Cozaar®)Losartan-Hydrochlorothiazide (Hyzaar®)Moexpril (Univasc®)Moexpril-Hydrochlorothiazide (Uniretic®)Valsartan (Diovan®)

ANTILEUKEMICPenostatin (Nipent®)

ANTIMALARIALHydroxychloroquine (Plaquenil®)Penostatin (Nipent®)

ANTINEOPLASTICCapecitabine (Xeloda®)Flutamide (Eulexin®)Levamisole(Ergamisol®)Porfimer Sodium (*Photofrin®)

ANTIPARKINSONIANSelegiline (Eldepryl®)

ANTISPORIATICAcitretin (Soriatane®)

Tazarotene (Tazorac®)

ANTIPSYCHOTICCarbamazepine (Tegretol®)Clozapine (Clozaril®)Pephenazine (Trilafon®)Prochlorperazine (Compazine®)Risperidane (Risperdal®)Thiothixene (Navane®)Ziprasidone (*Geodon®)

APPETITESUPPRESSANTSibutramine (Meridia®)

ASTHMA/ANTI-INFLAMMATORYTriamcinolone (Azmacort®)

CARDIOVASCULARAnagrelide Hydrochloride (Agrylin®)Atrovastatin (Lipitor®)Captopril (Capoten®)Carvedilol (Coreg®)Fenofibrate (TriCor®)Gemfibrozil (Lopid®)Lisinopril (Prinivil®, Zestril®)Ramipril (Altace®)

CHEMOTHERAPEUTICFluorouracil (*Efudex®)Interferon Alpha-2b (Intron® A)Interferon Alpha-n3 (Alferon®)

DIURETICChlorothiazide (Aldoclor®, Diuril®)Furosemide (Lasix®)Hydrochlorothiazide & Combinations(Accuretic®, Aldoril®, Atacand®,Avalide®, HydroDIURIL®, Inderide®,Maxzide®, Micardis®, Moduretic®,Prinzide®, Timolide®, Zestoretic®)Hydroflumethiozide & Combinations(Diucardin®)Metolazone (Mykrox®, Zaroxolyn®)Polythiazide (Renese®)Polythiazide-Prazosin (Minizide®)Triamtrene (Dyazide®)

Appendix B

80

ENDOMETRIOSISMANAGEMENTLeuprolide (Lupron®)

ERECTILEDISFUNCTIONSildenafil Citrate (Viagra®)

GASTROINTESTINALMesalamine (Pentasa®)Rabeprazole (AcipHex®)

MULTIPLESCLEROSISMANAGEMENTInterferon beta-1 a (Avonex®)

MUSCLERELAXANTDantrolene (Dantrium®)

OPTHALMICNorfloxacin (Chibroxin®)Methazolamide (Neptazane®)Trimethoprim-Polymyxin (Polytrim®)

ORGANREJECTIONPROPHYLAXISSirolimus (Rapamune®)Tacrolimus (*Prograf®, Protopic®)

PHOTOSENSITIZINGAGENTAminolevulinic Acid (Levulan®, Kerastick®)Verteporfin (*Visudyne®)

RETINOIDIsotretinoin (Accutane®)Tazarotene (Tazorac®)

SALIVARYAGENTCevimeline (Evoxac™)Pilocarpine (Salagen®)

SEDATIVE/HYPNOTICZaleplon (Sonata®)

*Indicates a 3% or greater incidence of photosensitivity reactions.

The information in this list was derived from the 2002 Physicians’ Desk Reference Companion Guide™, Side Effects Index, Photosensitivity, pp. 1357-1358. This list does not include photosensitizing drugs with an incidence described as “rare”, “less frequent”, “less common”, “infrequent”, “occasional”, “extremely rare”, or occurring in “some individuals”, “one case”, “at least one patient”, or “isolated cases”.

This list does not include all drugs that may cause photosensitivity.

Appendix B

81

GLOSSARY OF TERMS

Glossary of Terms

Dermis– Inner layer(s) of skin that lies just below the epidermis. Known as the “true” or “living” skin.

ElectromagneticRadiation – Radiation caused by changes in electric and magnetic intensity. The spectrum includes gamma rays, x-rays, ultraviolet, visible, infrared, radio and microwaves.

Epidermis – Outer layer(s) of the skin. The Stratum Corneum is the outermost layer of the epidermis.

Erythema – Abnormal redness of the skin.

Melanocytes – Cells that make pigment.

Micron – A measurement of length equal to one-thousandth of a millimeter or one millionth of a meter. (One strand of hair is approximately 100 microns wide).

Nanometer[nm]– A measurement of length equal to one-billionth of a meter (or one-thousandth of a micron).

Organic – Substances (chemicals) that contain the element carbon. Nearly all naturally occurring substances from plants and animals are “organic.”

Photosensitive – Sensitive or sensitized to the action of radiant energy.

Phototoxic – 1) Rendering the skin susceptible to damage (as sunburn or blisters) upon exposure to light and especially ultraviolet light. 2) Induced by a phototoxic substance.

Photoallergic – Of, relating to, caused by, or affected with an allergic sensitivity to light. Polymer – Substance, natural or synthetic, formed by a repeated combination (“chain”) of the same basic chemical compound. Common examples are “nylon” and silk.

SunProtectionFactor[SPF] – The multiple of time it takes for reddening to begin when sunscreen protected skin is exposed to sunburn wavelengths (primarily UVB) as compared to unprotected skin.

Ultraviolet[UV] – Electromagnetic waves that are shorter than visible waves, beyond the violet end, but longer than x-rays.

82

REFERENCES

Much of this work has been based upon the fifty-three (53) articles written by ninety-five (95) authors, as presented in the book “Sunscreens- Development, Evaluation and Regulatory Aspects” (Reference No 1). Within this book there are 1,000 (+) references, incorporated herein. In Chronological order:

Lowe, J.L., A. Shaath, M. A. Pathak (Eds.): Sunscreens – Development, Evaluation and Regulatory Aspects (Marcel Dekker, Inc., NY; 1997).

Kligman, L.H. Intensification of Ultraviolet – Induced Dermal Damage by Infrared Radiation, Arch Dermatol Res 272: 229-238 (1982).

Kligman, A. M., L. H. Kligman. Reflections on Heat,Br. J. Derm 110: 369-375 (1984).

Bissett, D. L., R. Chatterjee, D. P. Hannon. Chronic Ultraviolet Radiation …Photoprotective Effect of Topically Applied Chelators,Photochemistry and Photobiology 54: 215-223 (1991).

Burke, K. E., G. F. Combs Jr., E. G. Gross, K. C. Bhuya, H. Abu-Libdeh. The Effects of Topical and Oral Selenomethionine on Pigmentation and Skin Cancer Induced by Ultraviolet Radiation, Nutrition and Cancer 17: 123-137 (1992).

Lenz, E. Herbal Sun Care, Herbs for Health PP. 37-39 (May/June 1998).Jones, C. L. A. Avoiding Skin Cancer, Herbs for Health PP, 33-36 (May/June 1998).

Heinrich, U. Symposium: New Aspects of Light Protection and Carotenoids 4th Derma Days at the University of Witten, Germany(As reported in “Skin Care Forum” No. 19:P.6 (September 1998).

“Dermatology Times, PP. 55-56 (February 1999). Skernivitz, T. Tinted Sunscreen Offers Photosensitive Patients Improved Quality of Life, Dermatology Times (February 1999).

Sun & Skin News (… of the Skin Cancer Foundation) 16:4 (1999).Hamaker, A. Sun Protection, Day Spa PP. 30-42 (March/April 1999).Sayre, R. M., J. C. Dowdy, Photo [In-] Stability of Avobenzone,Allured’s Cosmetics and Toiletries 114:85-91 (May 1999).

Gadberry, R. J. Ask the Ingredient Expert, Dermascope PP. 24-28 (May/June 1999).

Reid, C. D. Chemical Photosensitivity, Les Nouvelles Esthetiques (Medical Section) PP. 199-206 (June 1999)

References

83

Califano, J. Outsmart Skin Cancer, McCalls’ Health PP. 79-82 (July 1999).

Morganti, P. and G. Fabrizi. Photoprotection by Sunscreens, Soap & Cosmetics PP.46-49 (July 1999).

Naylor, M. and Gasparro, F. What You and Your Patients Should Know About Sunscreens. Skin and Aging. June 1998. pp.44-50

On-line Medical Dictionary, © 1997-98 Academic Medical Publishing & CancerWEB

The Skin Cancer Foundation www.skincancer.org

Sandy Chira, AB Brown University, Skin Cancer: Tips on Prevention, Clues on Detection. Consultant, May 2007.

Bonita Potter & Barb Schroeder, Skin Cancer Risks in Transplant Recipients: Know the Facts. www.itns.org.

Nutritional Outlook, www.NutritionalOutlook.com. May 2008 Edition (p.52-54)

Lisa Barclay, MD, American Academy of Dermatology Issues Updated Position Statement on Vitamin D. www.medscape.com, July 16, 2009

Peter T. Pugliese, MD, Vitamin D: An Evolving Star. Skin Inc. Magazine, July 2009

Dietary Supplement Fact Sheet: Vitamin D, National Institute of Health

Creighton Study Shows Vitamin D Reduces Cancer Risk. Creighton University School of Medicine. June 2008

Curtis Cole, PhD, Determining Sunscreen Protection Against UVA. Johnson & Johnson Consumer Products Inc., Skillman New Jersey. January 2007

A. Fourtanier, F. Bernerd, C. Boullon, L. Marrot, D. Moyal, S. Seite, Protection of skin biological targets by different types of sunscreens. Blackwell Munksaard, Photodermatology Photoimmunology & Photomedicine, 2006.

Johnson & Johnson Vision Care Inc., http://www.jnjvisioncare.com/images/uv-damage-overview-image.jpg

Arlo J. Miller, M.D., Ph.D., and Martin C. Mihm, Jr., M.D., Melanoma. New England Journal of Medicine, July 6, 2006.

References

84

Michael E. Newman, Answers to burning questions on sunscreen and sun safety. Update, Summer 2008. (p.16-17)

Moyal DD, Fourtanier AM. Effects of UVA radiation on an established immune response in humans and sunscreen efficacy. Exp Dermatol 2002: 11 (suppl. 1): 28-32. Blackwell Munksgrand, 2002

Leah Armstrong, Which? exposes inaccurate SPFs on popular sunscreens. Cosmeticsdesign.com, June 2, 2009.

Robert and Carol Trow, Cancer and soft coral from the Red Sea. Skin wise P. 37-38, July 2009.

Yu-mei Chang, Jennifer H Barrett, D Timothy Bishop, Bruce K Armstrong, Veronique Bataille, Wilma Bergman, Marianne Berwick, Paige M Bracci, J Mark Elwood, Marc S Ernstoff, Richard P Gallagher, Adèle C Green, Nelleke A Gruis, Elizabeth A Holly, Christian Ingvar, Peter A Kanetsky, Margaret R Karagas, Tim K Lee, Loïc Le Marchand, Rona M Mackie, Håkan Olsson, Anne Østerlind, Timothy R Rebbeck, Peter Sasieni, Victor Siskind, Anthony J Swerdlow, Linda Titus-Ernstoff, Michael S Zens and Julia A Newton-Bishop, Sun exposure and melanoma risk at different latitudes: a pooled analysis of 5700 cases and 7216 controls. International Journal of Epidemiology, April 08, 2009.

Rada K. Tierney, New Age of Sunscreen. Medesthetics May/June 2008

Susan Erb, NP, Richard John, NP, and John Cannell, MD. Vitamin D. Advance for Nurse Practitioners, May 2007, Page 77-80.

http://www.fda.gov/nanotechnology/taskforce/report2007.pdf

http://www.tga.gov.au/npmeds/sunscreen-zotd.htm

Nanotechnology, Cosmetics in the Skin: Is there a Health Risk? G.J. Nohyneck, E.K. Dufour, M.S. Roberts, Skin Phamacol Physiol 2008; 21:136-149.

http://ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_o_009.pdf

http://www.bfr.bund.de/cms5w/sixcms/detail.php/7734

http://www.comseticsdatabase.com/special/sunscreens2008/report_nanotechnology.php

Mindy S. Goldstein, PhD. Nanomaterials in Personal Care: Opportunities and Safety Considerations. Cosmetics & Toiletries Magazine Vol. 123, No.12/December 2008, P.26-

http://www.cosmeticsdesign.com/content/view/print/232732

References

85

http://www.environ.co.za/contents/articles/vitamin_c.htm

http://www.environ.co.za/contents/articles/Varieties_of_vitamin_a.htm

Martin Weinstock, MD, PhD. Prevention and Progression of Actinic Keratosis. Advances in the Treatment of Actinic Keratosis, Supplement to the December 2009 Skin & Aging.

Darrell S. Rigel, MD. Individualizing Actinic Keratosis Management to Improve Patient Outcomes. Advances in the Treatment of Actinic Keratosis, Supplement to the December 2009 Skin & Aging.

Dr. Des Fernandes. Varieties of Vitamin A Used in Cosmetic Preparations Applied to the Skin. Copyright Environ Skin Care Ltd 2006.

Kaidbey, K.H.. Journal of the American Academy of Dermatology, 1990, 22(3): 449-452.

Mayo Clinic Proceedings. Vitamin D It’s not just for bones anymore. Digestion & Diet Health Monitor.

Kassandra L. Munger, MSc; Lynn I. Levin, PhD, MPH; Bruce W. Hollis, PhD; Noel S. Howard, MD; Alberto Ascherio, MD, DrPH . Serum 25-Hydroxyvitamin D Levels and Risk of Multiple Sclerosis. JAMA. 2006;296:2832-2838.

Susan Erb, NP, Richard John, NP, and John Cannell, MD. Vitamin D Research Suggests Broader Health Role. Advance for Nurse Practitioners. May 2007.

Environmental Working Group. Nanotechnology & Sunscreens. EWG’s 2009 Sunscreen Investigation, Section 4.

Marianne Placzek, Sabine Gaube, Urs Kerkmann, Klaus-Peter Gilbertz, Thomas Herzinger, Ekkehard Haen and Bernhard Przybilla. Ultraviolet B-Induced DNA Damage in Human Epidermis Is Modified by the Antioxidants Ascorbic Acid and D-α-Tocopherol. Journal of Investigative Dermatology (2005) 124, 304–307; doi:10.1111/j.0022-202X.2004.23560.x

References

86 Footnotes

1 Roni Caryn Rabin. Hazards: Indoor Tanning Is Linked to Skin Cancer (New York Times). New York Times. May 31, 2010.2 Dr. Des Fernandes. Varieties of Vitamin A Used in Cosmetic Preparations Applied to the Skin. Copyright Environ Skin Care Ltd 2006.3 A. Fourtanier, F. Bernerd, C. Boullon, L. Marrot, D. Moyal, S. Seite, Protection of skin biological targets by different types of sunscreens. Blackwell Munksaard, Photodermatology Photoimmunology & Photomedicine, 2006.4 Kaidbey, K.H.. Journal of the American Academy of Dermatology, 1990, 22(3): 449-452.5 Sandy Chira, AB Brown University, Skin Cancer: Tips on Prevention, Clues on Detection. Consultant, May 2007.6 Darrell S. Rigel, MD. Individualizing Actinic Keratosis Management to Improve Patient Outcomes. Advances in the Treatment of Actinic Keratosis, Supplement to the December 2009 Skin & Aging.7 Bonita Potter & Barb Schroeder, Skin Cancer Risks in Transplant Recipients: Know the Facts. www.itns.org.8 Yu-mei Chang, Jennifer H Barrett, D Timothy Bishop, Bruce K Armstrong, Veronique Bataille, Wilma Bergman, Marianne Berwick, Paige M Bracci, J Mark Elwood, Marc S Ernstoff, Richard P Gallagher, Adèle C Green, Nelleke A Gruis, Elizabeth A Holly, Christian Ingvar, Peter A Kanetsky, Margaret R Karagas, Tim K Lee, Loïc Le Marchand, Rona M Mackie, Håkan Olsson, Anne Østerlind, Timothy R Rebbeck, Peter Sasieni, Victor Siskind, Anthony J Swerdlow, Linda Titus-Ernstoff, Michael S Zens and Julia A Newton-Bishop, Sun exposure and melanoma risk at different latitudes: a pooled analysis of 5700 cases and 7216 controls. International Journal of Epidemiology, April 08, 2009.9 The Skin Cancer Foundation www.skincancer.org10 IARC Working Group. Sunbeds and UV Radiation. http://www.iarc.fr/en/media-centre/iarcnews/2009/sunbeds_uvradiation.php. 7/29/2009.11 Lisa Barclay, MD, American Academy of Dermatology Issues Updated Position Statement on Vitamin D. www.medscape.com, July 16, 200912 Peter T. Pugliese, MD, Vitamin D: An Evolving Star. Skin Inc. Magazine, July 200913 Mayo Clinic Proceedings. Vitamin D It’s not just for bones anymore. Digestion & Diet Health Monitor.14 Kassandra L. Munger, MSc; Lynn I. Levin, PhD, MPH; Bruce W. Hollis, PhD; Noel S. Howard, MD; Alberto Ascherio, MD, DrPH . Serum 25-Hydroxyvitamin D Levels and Risk of Multiple Sclerosis. JAMA. 2006;296:2832-2838.15 Susan Erb, NP, Richard John, NP, and John Cannell, MD. Vitamin D Research Suggests Broader Health Role. Advance for Nurse Practitioners. May 2007. 16 Dietary Supplement Fact Sheet: Vitamin D, National Institute of Health.17 www.cdc.gov/mmwr/preview/mmwrhtml/00015916.htm18 http://www.environ.co.za/contents/articles/vitamin_c.htm19 http://www.environ.co.za/contents/articles/Varieties_of_vitamin_a.htm20 Marianne Placzek, Sabine Gaube, Urs Kerkmann, Klaus-Peter Gilbertz, Thomas Herzinger, Ekkehard Haen and Bernhard Przybilla. Ultraviolet B-Induced DNA Damage in Human Epidermis Is Modified by the Antioxidants Ascorbic Acid and D-α-Tocopherol. Journal of Investigative Dermatology (2005) 124, 304–307; doi:10.1111/j.0022-202X.2004.23560.x21 Croda. The Science of Sun Defence UV Protection. Copyright 2009 Croda Europe Ltd.22 Rada K. Tierney, New Age of Sunscreen. Medesthetics May/June 200823 Robert and Carol Trow, Cancer and soft coral from the Red Sea. Skin wise P. 37-38, July 2009.24 Environmental Working Group. Nanotechnology & Sunscreens. EWG’s 2009 Sunscreen Investigation, Section 4.

FOOTNOTES

87

1993

Body

20% Zinc Oxide ProtectionWATER-RESISTANT

Contains Only Titanium & ZincWATER-RESISTANT

Tinted

Clear

1999

2001

2002

Individually customizable make-up

2007

2008

2009

2010

TiZOFor Ultra

Sensitive Skin

2011

FALLENELtd.

Fallene H s been Dedicated

to using the Best ingredientsin Sun creen for Over

Twenty years!

UVB UVA

Zinc Oxide

Titanium Dioxide

Octocrylene

Octinoxate

Oxybenzone

280nm

Avobenzone

Octisalate

Ecamsule (Mexoryl) ™ of L'Oréal

Octyl Dimethyl (Paba)

320nm 400nm

Chemical Sunscreen Filter

Light Spectrum in nanometers

Physical Sunscreen Filter

Zinc Oxide and Titanium Dioxide#1 Rated Sunscreen Filters

88 Notes

____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

NOTES

Fallene Ltd.

Copyright ©2010 Fallene, Ltd.

2555 Industry LaneWest Norriton, PA 19403

(610) 630-6800 1(800) 332-5536FAX: (610) 630-6202

www.totalblock.com

1993

Body

20% Zinc Oxide ProtectionWATER-RESISTANT

Contains Only Titanium & ZincWATER-RESISTANT

Tinted

Clear

1999

2001

2002

Individually customizable make-up

2007

2008

2009

2010

TiZOFor Ultra

Sensitive Skin

2011

FALLENELtd.

Fallene H s been Dedicated

to using the Best ingredientsin Sun creen for Over

Twenty years!

Therapeutic Sun Care A Guide to Light Protection · 2016. 4. 27. · II. The Sun’s Effect On Your...

Documents

Transcript of Therapeutic Sun Care A Guide to Light Protection · 2016. 4. 27. · II. The Sun’s Effect On Your...