Summary and Key Features
- •
UVB (290–320 nm) and UVA (320–400 nm) are the wavelengths responsible for human photoaging.
- •
Micronized versions of the inorganic sunscreen actives titanium dioxide (10–30 nm) and zinc oxide (10–200 nm) allow these agents to be used by many skin colors.
- •
Photochemical stability, the ability of a molecule to remain intact after absorbing a photon of energy, is a vital characteristic of an effective UV filter.
- •
The current FDA standard for sunscreen application is 2 mg/cm 2 , yet studies suggest that actual usage is only 25–50% of this amount.
- •
Factors contributing to sunscreen effectiveness include resistance to water immersion and sand abrasion, reapplication frequency, and film thickness.
- •
Sunscreens containing effective antioxidants, combination tinted sunscreens, and antioxidant-enriched tinted sunscreens can mitigate effects of long UVA1 and visible light.
See , , , and .
Introduction
The solar radiation that reaches the Earth is made up of approximately 50% visible light (VL), 45% infrared (IR) radiation, and 5–7% ultraviolet (UV) radiation depending on the location and time of the year. It should be noted that in the UV spectrum, only UVB (290–320 nm) and UVA (320–400 nm) reach the surface of the Earth; UVC is filtered out completely in the hemisphere. Sun exposure triggers a multitude of photochemical and photobiologic effects in skin. The main clinical effects after UV exposure can be observed as immediate pigment darkening (IPD), vitamin D production, persistent pigment darkening (PPD), erythema, delayed tanning, and exacerbation of inherited and acquired photosensitive skin disorders, with long-term effects including photoaging and skin cancer. According to the American Academy of Dermatology, skin cancer is the most common cancer in the United States, and current estimates are that one in five Americans will develop skin cancer in their lifetime.
Recent in vivo studies reported that VL is responsible for high levels of free radical generation on the skin, contributing to cutaneous premature photoaging; VL also can induce skin erythema and pigmentation in light skin phototypes and especially in dark skin phototypes. This evidence shows that VL can induce pigmentary alterations, especially in dark-skinned individuals, and can exacerbate photodermatoses and pigmentary disorders. There is an increased need for broad-spectrum protection covering the UV and VL parts of the spectrum. Antioxidants are crucial to provide such protection, since VL-induced damage is mainly reactive oxygen species (ROS) mediated.
Because solar exposure is the most preventable risk factor for all skin cancer and solar-induced hyperpigmentation, daily photoprotection is extremely important as well as other photoprotective measures including long-sleeved shirts, pants, wide-brimmed hats, and sunglasses with UV protection.
Regulatory Aspects
Sunscreens have been regulated by the US Food and Drug Administration (FDA) since the 1970s. In 1978, the FDA reclassified sunscreens from “cosmetics,” intended to minimize sunburn and promote tanning, to over-the-counter (OTC) “drugs,” intended to reduce the harmful effects of UV radiation (UVR) on skin structure and function. However, it was not until May 1999 that the FDA published its monograph addressing the testing and labeling of sunscreen products for the prevention of UVB damage (i.e., sunburn). The monograph was updated in 2011 to address formulation, labeling, and testing requirements for both UVB and UVA radiation protection. In 2019, the FDA issued an updated proposed rule on sunscreens that proposed to revise the requirements for sunscreen active ingredients, maximum sun protection factor (SPF) levels, broad-spectrum requirements (protection against both UVA and UVB rays), and dosage forms (e.g., cream, lotion, or spray), among other things. The proposed rule also included updates on how sunscreens are labeled to make it easier for consumers to identify key information. The FDA then called a deemed final order for certain requirements for active ingredients from the 1999 final monograph regulation for OTC sunscreen products that never took effect, and the labeling and effectiveness requirements from the final 2011 labeling and effectiveness testing rule. Meanwhile, a proposed order proposes changes to these requirements to bring them up to date with the current science. When finalized, the proposed order will fully replace the deemed final order with new requirements for sunscreens. This new proposed order has notable differences from the deemed final order that include a maximum labeled SPF of 60+.
History and Chemistry of Ultraviolet Filters
The reported use of a chemical sunscreen in the world was introduced in the United States in 1928; it contained benzyl salicylate and benzyl cinnamate. In the early 1930s, a product containing 10% Salol (phenyl salicylate) was commercialized in Australia. In 1935, lotions containing quinine oleate and quinine bisulfate could be found in the United States. In 1942, para-aminobenzoic acid (PABA) ointment was shown to be an effective sunburn protectant. During World War II, red petrolatum was used by US military, which led to extensive use of UV filters after the war.
Currently there are three types of UV filters:
- 1
Organic UV absorbers
- 2
Inorganic particulates
- 3
Organic particulates
Organic UV Absorbers
Organic UV absorbers or filters are compounds that absorb UV irradiation by their highly conjugated structure. The organic sunscreen active ingredients prevent sunburn by absorbing high-intensity UV rays with excitation of electrons to a higher energy state. Excess energy is dissipated by emission of higher wavelengths or by relaxation through a photochemical process such as isomerization or heat release. The UV filters in use can be classified as derivatives of the chemical structures PABA and para-aminobenzoates, salicylates, cinnamates, benzophenones, anthranilates, dibenzoylmethanes, and camphor derivatives. Table 23.1 shows the most common UV filters used in the United States, maximum concentration allowed, and maximum attenuation peak in nm.
| Active Ingredient | Maximum Concentration (%) | Maximum Attenuation Peak (nm) |
|---|---|---|
| UVA Absorbers | ||
| Avobenzone | 3 | 357 |
| Oxybenzone | 6 | 325 |
| Methyl anthranilate | 5 | 336 |
| Ecamsule | 10 | 345 |
| UVB Absorbers | ||
| Homosalate | 15 | 306 |
| Octocrylene | 10 | 303 |
| Octyl methoxycinnamate | 7.5 | 310 |
| Octyl salicylate | 5 | 307 |
| Phenylbenzimidazole sulfonic acid | 4 | 310 |
Inorganic Particulates
Titanium is the 9th most common element, and zinc ranks 24th in abundance in Earth’s crust. In the 1950s, it became commonplace to see lifeguards and fair-skinned children at the beach with solid white streaks of zinc oxide paste on their noses, lips, and cheeks. These products were messy and not conducive to widespread application.
Micronized versions of titanium dioxide (TiO 2 ) and zinc oxide (ZnO), with particle sizes averaging 10–30 nm for TiO 2 and 10–200 nm for ZnO, now allow these formulations to be nearly imperceptible on all but the darkest skin tones, making them much more appealing.
Traditionally, physical agents used to prevent sunburn were called sunblocks while chemical agents were sunscreens. The terminology is misleading because it suggests that the former merely scatter or reflect UVR. In fact, the physical (also called inorganic or insoluble) agents, titanium dioxide and zinc oxide, also act as semiconductors that absorb UVR and release it as heat. The use of the term chemical-free for sunscreens containing only physical, not chemical, sunscreen agents is also confusing for consumers, since all active and inactive ingredients have been obtained and/or combined through some chemical process. The FDA-approved maximum concentration of these agents in sunscreen is listed in Table 23.2 .
| Active Ingredient | Maximum Concentration (%) | Maximum Attenuation |
|---|---|---|
| Titanium dioxide | 25 | Broad spectrum |
| Zinc oxide | 25 | Broad spectrum |
Organic Particulates
The microfine organic particle is a new form of UV filter having characteristics of both organic and inorganic filters. Its unique property includes absorbing UVR like an organic filter and scattering and reflecting UV rays similar to an inorganic filter. MBBT (Methylene bis-benzotriazolyl tetramethylbutylphenol or Tinosorb M) is the first agent in this new class using microfine particle technology. It is a colorless, UV-absorbing organic solid that has been micronized to particles less than 200 nm in diameter. In the same way as with inorganic UV filters, the physical properties of microfine organic particles strongly depend on the particle size. MBBT that has been micronized at a particle size of 160 nm can attenuate about 85% of the UVR transmitted in a thin film with slight contributions from particulate scattering (10–15% is forward scattered and 3–5% is backward scattered or reflected). MBBT is an approved UV filter in the European Union, ASEAN, and MERCOSUR, at a 10% approved usage level.
Sun Protection Factor
The discovery of UVR in 1801 by Johann Wilhelm Ritter did not gather much attention in medical circles. Historically, the first known studies establishing the basis for sun protection factor assessment started in the 1930s, and the early publications were in the 1940s by H. Blum et al. and in the 1950s by R. Schulze. Blum described in his original paper the sunscreen protective factor “P”. Circa 1962, Professor Franz Greiter started working on and describing what is known today as the concept of sun protection factor (SPF) and introduced sunscreens with SPF labels. In the 1978 FDA proposed sunscreen monograph, outdoor and indoor SPF testing was described. At the time, the use of natural sunlight was accredited to be much closer to actual sunscreen use, which would include heat, humidity, and the full solar spectrum. On the other hand, testing sunscreen under natural sunlight can be difficult due to variability in weather conditions, changes in cloud cover, and changes in radiation intensity during the exposure. The use of indoor solar simulators made of xenon arc lamps became more popular with the advantages of providing a constant spectrum and high UV power output. One important note is that the ratio of UVA (320–400 nm) and UVB (290–320 nm) radiation in sunlight from 9 a.m. to 3 p.m. is constant and equal to 21:1, and the standard solar simulators used in sunscreen have a UVA/UVB test ratio of around 8:1.
SPF is not an absolute protection rating; it is a relative measure of the protection provided by a sunscreen to prevent sunburn. An SPF 25 product (if applied at the proper amount) will allow you to stay in the sun 25 times longer than you could if you did not have on the sunscreen. For example, if you would normally sunburn after 15 minutes of sun exposure, an SPF 25 product, if applied at the proper amount, would allow you to stay in the sun 25*15 = 375 minutes before you would have a mild sunburn.
The SPF is assessed in an in vivo test that estimates the protective efficacy of a sunscreen against erythema as a clinical endpoint. At least 10 healthy individuals are required to support a clinical SPF label claim. Subjects must be in good general health and have Fitzpatrick skin type I, II, or III to be included in the study. This is a 3-day clinical study. On day 1, after determining that the subject is qualified for participation in the study, the technician will administer a timed series of five UV doses using a solar simulator with characteristics specified in the 2011 FDA monograph. Five or six UV doses increasing in 25% increments are administered. On day 2, the subject is instructed to return to the test center within 16–24 hours after completion of the UV dose. A trained technician will evaluate the skin response to the UV exposure to determine the minimal erythema dose (MED). This initial assessment is called the initial unprotected MED. According to the 2011 FDA monograph, the MED is the smallest UV dose that produces perceptible redness of the skin (erythema) with clearly defined borders at 16–24 hours after UV exposure. Test sites are demarcated using an indelible surgical pen on the subject’s back. In a typical study four or six horizontally oriented rectangular sites with dimensions of 5 × 10 cm can be marked on subject’s back depending on the anatomy. The trained technician will apply 2 mg per cm 2 of each test product and the standard reference sunscreen in its respective designated rectangle. The tested sunscreens (a new sunscreen product and the reference standard sunscreen) will be applied by “spotting” the material across the area and gently spreading using finger cot. The active ingredients of the standard sunscreen designated as the padimate O/oxybenzone standard are 7% padimate O and 3% oxybenzone. A minimum of 15 minutes of waiting time is required after the application of the sunscreen product and standard reference sunscreen before the administration of the UV dose on the protected sites. The protected UV exposure series are based on the target SPF value and the initial unprotected MED. The unprotected skin MED series of exposure is also repeated on day 2. On day 3, the subject is required to return to the testing laboratory within 16–24 hours after completion of the unprotected doses and protected doses for evaluation of the MED responses. The SPF tested in one individual value is calculated as:
SPF=ProtectedMEDRepeatFinalUnprotectedMED
The mean SPF and standard deviation (SD) will be calculated from valid individual SPF values. The labeled SPF value for a tested product is determined as the largest whole number less than the following calculation:
LabeledSPF=MeanSPF−(t*SE)
Mean SPF is the arithmetic mean of at least 10 individuals.
t is the value from student’s t distribution table corresponding to the upper 5% point with n – 1 degrees of freedom.
SE is the standard error of the mean.
For the measured value of the test product to be valid, the mean value of the padimate O/oxybenzone standard must fall within the standard deviation range of the expected SPF (i.e., 16 ± 3.43).
For measuring UVA protection, in 2011 the FDA mandated the use of an in vitro critical wavelength (CW) for testing. The CW test is conducted by applying the test product to three different polymethyl methacrylate plates at a density of 0.75 mg/cm 2 after a preirradiation dose of 800 J/m 2 (the equivalent of four times the MED of Fitzpatrick skin type II) is delivered. UV transmittances are then measured from 290–400 nm. CW is defined as the wavelength at which 90% of the total area under the absorbance curve occurs. To support a claim of “broad-spectrum,” the sunscreen must have a CW of ≥370 nm.
The first 1978 FDA proposed rule monograph required labeling that included “apply liberally before sun exposure and re-apply after swimming or excessive sweating.” In the 1999 final rule, the language was modified to “re-apply as needed or after towel drying, swimming, or after ‘sweating’ (or) ‘perspiring.’” The 2007 proposed amendment to the final monograph proposed rule gave notice of the FDA’s intention to require instructions for reapplication “at least every 2 hours” to “avoid lowering protection.” The proposed rule cites one study conducted in Galveston, Texas, as support for the 2-hour reapplication rule. Recent studies demonstrate that sunscreens remaining on the skin provide the original protection for as long as 6 hours if applied correctly and are not intended for use in swimming or sweating conditions.
Sunscreens can be physically rubbed off by toweling or washed off when swimming or with heavy sweating. Since swimming and sweat-inducing sports are most commonly done in warm weather and as daytime outdoor activities, the ability of a sunscreen to maintain its filtering abilities under wet conditions is critical. Water resistance is defined as maintenance of the labeled SPF value after 40 minutes or 80 minutes of water immersion in a freshwater pool, whirlpool, or Jacuzzi, consisting of two 20-minute periods of moderate activity separated by a 20-minute rest period until completing 40 or 80 minutes of immersion and concluded by air drying without toweling. The claims “waterproof,” “sweatproof,” or provide “all-day protection” are not approved claims because the FDA does not believe these are accurate statements.
Also in 2011, the FDA made several changes to the labeling of sunscreens. For broad-spectrum sunscreens with SPF ≥15, the labels state that the product helps prevent sunburn and, if used as directed with other sun protection measures, decreases the risk of skin cancer and early skin aging caused by the sun. This class of product will elaborate on limiting time in the sun, especially from 10 a.m. to 2 p.m., and advise users to wear long-sleeved shirts, pants, hats, and sunglasses. For sunscreens that are not broad spectrum or are broad spectrum but with an SPF ≤15, these claims will not be allowed on the label, which may only claim that the product helps to prevent sunburn. Box 23.1 shows the warnings that sunscreens need to comply according to labeling in regard to water-resistant and nonwater-resistant products.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
