INTRODUCTION

Increased outdoor leisure time, decreased clothing coverage, a diminishing stratospheric ozone layer, and the rise in popularity of indoor tanning have added up to a significant increase in ultraviolet (UV) radiation exposure in the last century. Skin cancer represents over 50% of all cancers in the US annually; the incidence of melanoma alone has more than tripled in the past two decades. Although UV radiation’s role as a cutaneous carcinogen was reported in the medical literature as early as the 1930s, and in the lay press in the 1940s and 1950s, general public recognition of the danger is a much more recent phenomenon. Additionally, increasing awareness of the causal relationship between UV exposure and the signs of aging, including wrinkling and dyspigmentation, has triggered widespread interest in sun protective products as cosmeceuticals.

In 1978, the US Food and Drug Administration (FDA) reclassified sunscreens from ‘cosmetics’, intended to minimize sunburn and promote tanning, to over-the-counter ‘drugs’, intended to reduce the harmful effects of UV radiation 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. Although implementation was scheduled for December 2002, the effective date of the sunscreen monograph was delayed pending the development of a proposed amendment to define requirements for broad-spectrum UV coverage including UVA. As of August 2007, the FDA proposed new regulations that address formulation, labeling, and testing requirements for both UVB and UVA radiation protection. At the time of this writing, publication of set rules is pending definitive review of all suggestions and comments from the American Academy of Dermatology and general public.

CHEMICAL SUNSCREENS

The first commercial chemical sunscreen was introduced in 1928; it contained benzyl salicylate and benzyl cinnamate. In 1942, p-aminobenzoic acid (PABA) ointment was shown to be an effective sunburn protectant. This advance led to the development of many new sunscreen agents. In 1999, the FDA monograph included 14 chemical sunscreen agents considered safe and effective for use in over-the-counter (OTC) products.

The FDA-approved chemical sunscreens and the maximum allowed concentration for each are listed in Table 20.1. These ‘sunscreen active ingredients’ are defined as absorbing, reflecting, or scattering radiation in the ultraviolet range at wavelengths of 290–400 nm. The chemical (also called organic or soluble) sunscreen active ingredients prevent sunburn by absorbing UV radiation as photons of light energy that are transformed into harmless long wave radiation and then re-emitted as heat. The FDA defined maximum, rather than minimum, concentrations of each to avoid subjecting consumers to unnecessarily high levels of any active ingredient in sunscreen combination products. This provision also recognizes that final product testing, not the concentration of each active ingredient, determines efficacy.

Table 20.1 Sunscreen active ingredients: chemical

PHYSICAL SUNSCREENS

Opaque topical agents applied thickly on the skin surface have been used for decades to protect against sunburn. During the Second World War, red veterinary petrolatum was used by the military as a physical sunblock. 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. Over the last decade, cosmetic industry technology has been applied to the development of micronized versions of titanium dioxide and zinc oxide. With particle sizes of less than 0.2 micrometers, these formulations are 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 UV radiation. In fact, the physical (also called inorganic or insoluble) agents, titanium dioxide and zinc oxide, also act as semiconductors that absorb UV radiation 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 20.2.

Table 20.2 Sunscreen active ingredients: physical

RATING EFFICACY

With appropriate ultraviolet protection, exposed individuals do not suffer significant cutaneous DNA damage, sunburn cell formation, or immunosuppression. Clinically, sunscreen use significantly reduces the occurrence of actinic keratoses, nonmelanoma skin cancer, and skin aging. Daily application of sunscreen decreases the number of acquired nevi in children. Although intermittently raised as an issue, sunscreen use has not been proven to cause significant secondary vitamin D deficiency and will be addressed later in the chapter.

The ultraviolet spectra relevant to cutaneous damage are UVB (290–320 nm) and UVA (320–400 nm). Ultraviolet A radiation is further classified as UVA II (320–340 nm) and UVA I (340–400 nm). Clinically, excessive acute UVB exposure results in the classic sunburn. Multiple acute UVB assaults early in life have been linked with basal cell carcinoma and melanoma. The development of actinic keratoses and squamous cell carcinoma are more closely causally linked to chronic UVB exposure. Absorption of UVB by DNA mutates the p53 tumor suppressor gene and initiates the formation of pyrimidine dimers, an elevated level of which are mutagenic and linked to cutaneous carcinogenesis.

UVA may be a more silent threat than the erythemogenic UVB. A significant amount of UVB is screened by the stratospheric ozone layer, so terrestrial surface sunlight contains 20 times more UVA than UVB. Unlike UVB, UVA can penetrate window glass, and is relatively unchanged by time of day, season, and altitude. UVA can produce tanning and dyspigmentation without preceding erythema. The longer wavelengths penetrate deep into the dermis causing many of the histologic and clinical changes associated with photoaging. UVA I causes immunosuppression through the depletion of Langerhans’ cells and reduced activity of antigen-presenting cells. UVA also indirectly damages DNA through the formation of oxygen free radicals, mechanisms thought to contribute to carcinogenesis. Indeed, studies in animal models suggest that UVA may play a significant role in the development of malignant melanoma.

Sunscreen ingredients differ in their absorption spectrum, as shown in Table 20.3. Ideally a sunscreen should provide protection against the full spectrum of ultraviolet radiation. Until now most of the focus of the FDA’s attention has been on reducing exposure to UVB light. The sun protection factor (SPF), which measures UVB protection, was the only internationally standardized measure of a sunscreen’s ability to filter UV radiation. It is the ratio of the UV energy required to produce a minimal erythema dose (MED) on sunscreen-protected skin to the UV energy required to produce a MED on unprotected skin (Box 20.1). The MED is the quantity of energy required to produce the first perceptible redness reaction of the skin with clearly defined borders. Energy is delivered utilizing a filtered light source simulating the solar emission spectrum, with 94% of its output between 290 and 400 nm. (This mimics sunlight at sea level at a zenith angle of 10°.) For any given product, measurement must be done on between 20 and 25 test subjects of Fitzpatrick skin types I, II, and III. Test material is applied to an area of at least 50 cm² at a thickness of 2 mg/cm².

Table 20.3 Absorbance range of selected sunscreen active ingredients

The SPF of a given OTC topical sunscreen is determined by testing of that product as above. In accordance with FDA regulations, multiple sun protective active ingredients can be combined as long as each contributes a minimum SPF of at least 2 to the finished product. This requirement is meant to avoid the addition of unnecessary ingredients. FDA will revise some of the existing SPF testing procedures to decrease the health risk to persons enrolled in the SPF test and further enhance accuracy of SPF values.

It is important to note that certain ingredients are incompatible and, if combined, will reduce the final SPF of a product. For example, avobenzone is unstable when combined with cinnamates such as cinoxate, but is both stable and effective when combined with octocrylene. Conversely, combining other active ingredients can increase the level of sun protection by improving photostability. Both avobenzone and oxybenzone have been reported to undergo degradation after UV irradiance. The physical sunscreen ingredients, titanium dioxide and zinc oxide, have been shown to improve the survival of chemical sunscreens in vitro. The FDA is recognizing new combinations of active ingredients of avobenzone with either zinc oxide or ensulizole.

Furthermore, the FDA is amending its existing 1999 monograph and changing the highest SPF values from 30 + up to 50 +. When data that support accurate testing of sunscreens higher than 50 are reproduced, revising the upper limit of SPF will again be permitted in labeling.

Additionally, the proposed rule renames ‘SPF’ from ‘sun protection factor’ to ‘sunburn protection factor’, and sunscreen product labels would be required to include ‘UVB’ alongside ‘SPF’ so that consumers know that SPF values reflect UVB sunburn protection. Despite the proposed changes and improvements in SPF guidelines, there are still significant limitations. For example, thickness of application used to measure SPF may be unrealistic under ordinary, nontest conditions, thereby giving the consumer false confidence while significantly lowering the functional SPF. Moreover, people who use high SPF value sunscreens (who might otherwise have limited their ultraviolet exposure due to a fear of sunburn) may remain outdoors longer and accumulate more ultraviolet damage.

Regulations concerning UVA were delayed until recently since reliable testing methodologies were not available. However, the new proposed regulations address manufacturing, testing, and labeling of UVA sunscreens. Sunscreen manufacturers will now have to post the degree of protection afforded by a particular product against UVA rays. The scale of one to four stars corresponding to low, medium, high or very high UVA protection is to be prominently displayed on OTC sunscreen products near the SPF rating (Figs 20.1 and 20.2). Because consumers are familiar with SPF numbers, the FDA believes there may be confusion if UVB and UVA protection levels were both identified by numbers. Since star rating has been used in a variety of industries (e.g. hotels and restaurants), the FDA expects consumers will learn how to use this information to select the appropriate sunscreen, as they have done with SPF values. Furthermore, the product will bear a ‘no UVA protection’ marking on the front label if the sunscreen does not provide even a low level of protection.

Fig. 20.1 The principal display panel.

Adapted from http://www.fda.gov/cder/drug/infopage/sunscreen/qa.htm

Fig. 20.2 Proposed labeling configuration for UVA protection.

Adapted from http://www.fda.gov/cder/drug/infopage/sunscreen/qa.htm

Table 20.4