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SUNSCREEN SAFETY
Sunscreens have been utilized for decades with an excellent safety record, but usage patterns and recommendations have evolved significantly over time. In the past, sunscreens were primarily applied inter-mittently during times of intense sun exposure; however, as knowledge of their protective effects grew, this led to the current recommendation for daily use. Sunscreens are also incorporated into a broad array of personal care products. In the 2003โ2004 National Health and
Nutrition Examination Survey, high exposure to organic UV filters was demonstrated in that oxybenzone was detected in 96.8% of urine samples.
The major established adverse effects of sunscreens are minor skin irritation, which is common, and allergic contact dermatitis, which is rare. These reactions are often due to ingredients in the base of the product, such as fragrance or preservatives. Between 1999 and 2009, the organic compounds most often responsible for the rare instances of allergy or photoallergy in North America were oxybenzone and avobenzone41a. However, in Europe there has been an increasing number of reports of contact allergy and photocontact allergy to octocrylene. One speculation is that this is due to the use of topical NSAIDs (particularly ketoprofen) which cross-react with octocrylene and benzophenones.
Concerns have been raised, especially in the lay press, suggesting that some sunscreen agents are mutagenic or carcinogenic or have adverse hormonal effects in various in vitro and animal studies. These concerns relate primarily to retinyl palmitate, benzophenones, and nanoparticle titanium and zinc oxides. Although retinoids are known to be anti-carcinogenic, there is evidence that retinyl palmitate, when used as an additive in sunscreens and other personal care products, may absorb radiation and could theoretically lead to photodamage. Nanoparticles of titanium and zinc oxides could theoretically cause toxicity if they were to penetrate into the dermis, but studies show that such penetration does not occur in normal human epidermis (but can occur via hair follicles). While nanosized metal oxides may generate reactive oxygen species (ROS) when exposed to UV light, potential toxicity from ROS production is minimized by coating the particles with compounds such as silica or aluminum oxide. Finally, in animal studies, benzophenones were found to have estrogen-like effects and there is a single study in which decreased fecundity was reported in men with high exposure to these agents.
In 2019โ2020, the FDA published two randomized trials assessing plasma concentrations of organic UV filters under maximal use conditions. In the initial pilot study of 24 participants, sunscreens containing avobenzone, oxybenzone, octocrylene, and ecamsule were applied at 2โmg/ cm to 75% BSA four times daily for four days. Plasma concentrations of all four filters were >0.5โng/ml after four applications on day 1. The expanded follow-up study included 48 volunteers who applied sunscreens with six active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate), again at 2โmg/cm to 75% BSA, but with a modified dosing protocol of one application on the first day followed by four times daily on days 2โ4. All six filters reached systemic concentrations above the threshold following only one application.
The clinical effects of systemic absorption of organic UV filters are presently unknown. At the time of writing, no available data suggest that any organic filters need to be avoided for safety reasons. While ongoing evaluation of sunscreen safety is appropriate, physicians should stress that the overall riskโbenefit analysis favors sunscreens as safe and a necessary component of a preventive health strategy. Concerned patients may use physical blockers containing zinc and titanium oxides, acknowledging that a possible association of sunscreen use with frontal fibrosing alopecia has been reported in observational studies, but there is a lack of causal evidence to date to support the relationship.
In 2021, a private laboratory undertook a study to examine 293 batches of sunscreens and after-sun products from multiple manufacturers for the presence of benzene, a known carcinogen. Benzene was identified at concentrations >2 ppm (the maximum concentration allowed by the FDA when use is unavoidable) in 4.7% of the products, primarily spray and gel formulations. This was followed by manufacturer recalls48a.
Environmental Effects
Questions have also been raised as to the possible environmental impact of ubiquitous sunscreen use. Organic UV filters are detectable in surface water throughout the world, even reaching the Arctic. A major concern is that organic filters, in particular oxybenzone, may promote bleaching of coral reefs. Bleaching represents a response to environmental stressors in which corals expel symbiotic algae and turn white; coral death may follow.
A 2016 study reported an association between oxybenzone exposure and coral bleaching under laboratory conditions, as well as in vitro toxicity to coral cells. The possibility of conversion of oxybenzone to phototoxic glucoside conjugates by sea anemones and corals has been raised51a. However, limited conclusions can be drawn from these results, which may not accurately reflect real-world exposure conditions. Perhaps more importantly, coral bleaching is thought to be primarily driven by climate change, among other factors unrelated to sunscreen. Nonetheless, this study influenced legislation passed in Hawaii and other localities prohibiting sale and distribution of sunscreens containing oxybenzone and octinoxate. In 2021, the FDA published a notice of intent to prepare an environmental impact statement for oxybenzone and octinoxate under the National Environmental Policy Act. While awaiting more definitive data, conscious consumers should be directed to use inorganic filters, which pose fewer environmental concerns.
Sunscreen and Vitamin D Status
Some researchers believe that sunscreens may actually be deleterious to health by blocking the production of vitamin D. The first step in the production of this important nutrient is the photochemical conversion within the epidermis of 7-dehydrocholesterol to previtamin D by UVB radiation (see Fig. 51.11). Sunscreens that are effective at filtering UVB photons can result in decreased levels of vitamin D. However, the majority of human studies that measured serum vitamin D levels in sunscreen users (as compared to non-users) found that the levels, though reduced, remained within the normal range. In addition, studies have shown that darkly pigmented individuals, women, and in the wintertime individuals who live in northerly climes all have reduced levels.
Recently, scientists in the fields of nutrition and bone metabolism have presented data suggesting that individuals who have serum vitamin D levels in the low normal range may actually have insufficient vitamin D for optimum health. Some of these studies suggest that not only do these low normal or โinsufficientโ levels of vitamin D adversely affect good musculoskeletal health, but they may also increase the risk of cancer, immune dysfunction, and a broad range of other diseases. A recent systematic review found an association between vitamin D deficiency (<20โng/ml) and greater Breslow depth and higher mortality rate in patients with melanoma, but causality has not been established.
Controversy has arisen in part because scientists cannot agree on what constitutes the โnormalโ range for serum 25-OH vitamin D levels and similarly cannot agree on the minimum recommended daily intake for the vitamin. Although vitamin D can be obtained from foods such as fish oils, in developed countries the more common sources are vitamin D-fortified milk and milk products, as well as vitamin supplements. In 2010, the Institute of Medicine issued a consensus statement regarding the recommended dietary allowance for vitamin D โ 600โIU per day, except for those over 70 years of age in whom 800โIU per day was recommended. Unfortunately, the tanning salon industry continues to promote the concept that UV light exposure and tanning represent the optimum way to assure healthy vitamin D metabolism.