History

Creams to protect the skin against sunburn first emerged in the 1940s. In 1944, Benjamin Green invented red veterinary petrolatum, a greasy material, in order to protect soldiers and himself against UV light in World War II. This substance mixed with cocoa butter and coconut oil as eventually developed into Coppertone suntan cream. In 1988, the US Food and Drug Administration (FDA) approved a sunscreen product called avobenzone, which is a UVA-only filter. Until that point, the only approved filters were UVB filters that incidentally had UVA protection. The industry has now evolved; there are more than 30 different UV filters approved worldwide to protect against exposure to sunlight. The FDA regulates the chemicals used in sunscreens and, as of 2012, has limited the claims for sun protection factor (SPF), how waterproof a product is, and the length of time it remains effective. Thus, the United States still has far fewer protects approved by the FDA for market than the European countries do. For example, Tinosorb M and Tinosorb S (Bemotrizinol) are ingredients used for UVA protection, with peak absorption at 310 nm and 340 nm, that are not yet approved in the United States.

Mechanism

Sunscreens should have certain basic features. They should be water resistant, hypoallergenic, photostable, and should not penetrate the skin. They should also have the ability to dissipate absorbed light energy without forming reactive intermediates or harmful byproducts. Typically sunscreens contain both organic and inorganic UV filters that combined are broad-spectrum and protect against the entirety of the UVA and UVB range. UV filters are classified in 2 groups and many sunscreens today combine both types of filters in their formulations.

Organic Filters

The first group is chemical or organic filters that usually come in a liquid form. It is commonly found in a liquid formulation or as a water-based medium. Most organic filters have aromatic compounds conjugated with carbonyl groups. Organic filters absorb high-energy photons. Electrons in their benzene rings get excited and absorb in the UV range. This energy becomes dissipated as heat or light in a longer wavelength.

At present there are 15 organic filters approved in the United States but, as previously mentioned, many more are used worldwide. There are only 2 organic filters, oxybenzone and avobenzone, that protect against UVA rays in the United States. Oxybenzone is one of the most widely used UVA organic filters; it can absorb UV radiation from 270 to 350 nm with absorption peaks at 288 and 350 nm. Although it is an effective filter, there are a few controversies surrounding its use. There are some in vitro and in vivo studies that have highlighted potential effects of oxybenzone as a hormone modulator. In 2004, Janua and colleagues performed a single-blinded human study in which 15 men and 17 postmenopausal women applied a cream containing 10% oxybenzone(weight/weight) to their entire bodies at a dose of 2 mg/cm ² . After 4 hours of sunscreen application with oxybenzone, male patients had lower levels of estradiol and testosterone, whereas inhibin B was slightly increased. Female patients showed a decrease in testosterone within the first 24 hours. However, in both male and female patients, after 4 days of daily topical application, the investigators found no significant differences in the measured serum hormone levels between the treatment and control groups among either men or women. The study concluded that the differences in hormone levels were not related to the sunscreens containing oxybenzone. Despite such controversy, up to 6% oxybenzone is still approved for use in cosmetic products in the United States. Avobenzone is an organic filter that protects from 310 to 400 nm. It is the only UVA long-range filter approved by the FDA but is extremely unstable, meaning it degrades after 1 hour of exposure. Thus, it must be stabilized in the final formulation. There are many classes of organic filters, including dibenzoylmethane, benzophenone, p-aminobenzoate, salicylate, camphor, and cinnamate derivatives. Two of the new UV filter classes being used worldwide are triazones and benzotriazoles. With triazones, the molecular weight is greater than 500 Da, which reduces skin penetration. This group has higher absorption coefficients, better antiinflammatory effects, and is highly photostable. One such filter, Tinosorb S, has been able to improve the photostability of other UV filters in a sunscreen. Tinosorb A2B, approved in Europe, is a new filter that protects in the range from 290 to 340 nm, which is unique because it covers the gap between pure UVA or UVB filters.

Inorganic Filters

The second group is inorganic filters, previously classed as physical filters. Inorganic filters are minerals that reflect and scatter UV light, and have a small amount of absorption as well. These sunscreens have insoluble particles. The most well-known inorganic filters are titanium dioxide and zinc oxide. Historically, these mineral filters had poor particle dispersion and were thick and difficult to apply. They created an opaque film on the skin and were comedogenic, which decreased their appeal. Now these materials can be micronized to less than 100 nm and have broader refractive abilities and better protection in the UVB range. They are easier to apply and spread over the skin. However, these materials are not approved in a spray form because of potential toxicity to the lungs. The penetration ability of nanoparticles in the skin is still a particular focus of research, especially to skin that is already sun damaged. There remains a need for further research on the safety profiles of these specific products.

In addition, Tinosorb M (already approved in Europe) is under development. It is created as organic microparticles that can be dispersed in water, and it has good photostability and broad-spectrum action. It is able to reflect, absorb, and scatter UV radiation, giving it the properties of both organic and inorganic filters.

One warning for patients is that many sunscreens are labeled as “natural.” This term commonly refers to aforementioned sunscreens that contain only the minerals zinc oxide or titanium dioxide as active agents. These mineral sunscreens in general are less likely to have chemicals such as avobenzone that may induce allergic reactions or skin irritation. It is important again to be aware that these products may not offer complete sun protection.

Regulation

Sunscreen labels can be confusing. In 1956, Rudolf Schulze used the term protection factor, now called SPF. SPF is the quotient of the minimal erythema dose with applied sunscreen and the minimal erythema dose without sunscreen. It is an indication of protection against UVB radiation only. It is a faulty system because a sunscreen’s effectiveness varies with skin type, amount applied, frequency of reapplication, formulation of the product, and activities such as swimming.

Although the FDA does not support that any sunscreen less than an SPF of 15 can help prevent skin cancer, it also states that there is no evidence to support any increased efficacy in a sunscreen product with an SPF greater than 50. Thus, the FDA does not allow any sunscreen to advertise an SPF greater than 50. All such high-SPF sunscreens can only note on the label that the SPF is 50+. According to the FDA, a high SPF does not correlate with any UVA protection. SPFs greater than 50 may inflate people’s sense of protection, which can lead to prolonged exposure. In 2006, the European Commission gave a recommendation on the effectiveness of sunscreen that included a UVA protection factor/SPF ratio of at least 1:3.

There is no UVA rating system in the United States. However, the FDA has certain labeling requirements. It has mandated that any sunscreens with a label “broad-spectrum” must protect against from UVB and UVA rays. In 2011, the FDA ruled that, in order to define a product as broad-spectrum, the product’s critical wavelength had to be greater than or equal to 370 nm. “The critical wavelength describes the range of protection over the entire UV spectrum (290–400 nm) and is the wavelength at which 90% of the cumulative area under the total absorbance curve occurs. The longer the critical wavelength is, the broader the UVA protection of the product.” This label is only a pass/fail test.

Water resistance has a large effect on the quality of a sunscreen. The FDA states that a product can be labeled water resistant only if there is no decrease in SPF level after 2 baths of 20 minutes. In addition, the FDA does not allow sunscreens to be labeled sunblock, sweat-proof, waterproof, or all-day.

New Products

There may be a few new products under development that attempt to protect against sun damage via new mechanisms. There have been a few studies recently of the effect of the DNA repair enzymes photolyase and endonuclease. In a recent randomized clinical study, the clinical and molecular effects of sunscreens that included DNA repair enzymes were compared with traditional sunscreens in 28 patients with diagnosed actinic keratosis, a precursor of squamous cell carcinoma. The main outcome measures included hyperkeratosis, field cancerization (as measured by fluorescence diagnostics), and levels of cyclobutane pyrimidine dimers (CPDs) in skin biopsies. A similar effect on hyperkeratosis was found, but the addition of DNA repair enzymes to sunscreens was more effective in reducing field cancerization and CPDs than sunscreens alone. DNA repair enzymes may therefore be added to sunscreens in the future.

The FDA has not approved many new products in the last 10 years. Most sunscreens that are advertised as broad-spectrum in the United States contain the chemical oxybenzone or avobenzone to block UVA radiation. The most recent chemical approved for blocking UVA radiation is ecamsule, an organic compound.

Unlike avobenzone, which is not intrinsically photostable and requires photostabilizers to prevent degradation, ecamsule is a photostable organic UVA absorber, so it does not significantly break down when exposed to UV light. The UVB range is 290 to 320 nm, and the UVA range is 320 to 400 nm. Ecamsule is stated to provide protection in the 290-nm to 400-nm range, with peak protection at 345 nm. Ecamsule should be combined with a UVB-blocking agent because it does not provide coverage for the entire UV spectrum.

Awareness

In 2012, the FDA officially announced that only a sunscreen with an SPF of 15 or higher may permitted to be marketed as able to reduce the risk of skin cancer. There are many sunscreens on the market that are labeled with an SPF less than 15 and that are still permitted to be sold. Patients should be aware that there is no evidence that an SPF less than 15 has any preventive role against cancer. Per the FDA, it is recommended to use a water-resistant, broad-spectrum sunscreen with an SPF of 30 or more for an extended outdoor activity.

It is not only important to advise patients on their risk of skin cancer from UV exposure but also key to counsel them on risk of cancer recurrence once they have had a cancer resected. A recent study from Ireland interviewed 250 patients who underwent excision of basal cell carcinomas. Only 28.8% of patients acknowledged that they understood that the pathology of the lesion removed was basal cell carcinoma and that there was an increased risk of recurrence of a similar lesion in the next 3 years. Women and patients less than 65 years of age were significantly better informed about their diagnosis than men ( P <.021 and P <.001 respectively). Of note, although 76.8% of patients undertook some form of outdoor activity every day, only 22.8% wore sunscreen every day. It is key to communicate not only the patient’s final pathology after a skin cancer is resected but what their recurrence risk is and the benefits of sun protection; possibly even more in male patients in order to increase earlier rates of detection.

Limitations of Sunscreen

Although routine use of sunscreen is of utmost importance, finding shade, wearing wide-brimmed hats and clothing to cover exposed areas, and wearing UV-blocking sunglasses should be emphasized as well. It is important to counsel patients that, if they are using a higher-SPF sunscreen, not to be enticed into staying in the sun longer. Patients should be advised to apply sunscreen everywhere that is exposed and to apply at least 30 mL (1 oz) of sunscreen 15 minutes before going outside. Patients should also be educated that they need to reapply at least every 2 hours regardless of what the SPF of their sunscreen is so that they avoid overexposure to UVA and UVB rays.