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The efficacy and safety of sunscreen use for the prevention of skin cancer

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Several well-conducted randomized controlled trials with long follow-up showed that sunscreen use reduces the risk of squamous cell and melanoma skin cancers.

Commercial sunscreens protect against the skin-damaging effects of ultraviolet radiation through either chemical or physical ingredients.

The Canadian Dermatology Association recommends the use of an adequate dose of a broad-spectrum sunscreen with a sun protection factor of at least 30 for most children and adults, as part of a comprehensive photoprotection strategy.

Emerging evidence suggests that some chemical sunscreen ingredients are systemically absorbed, but the clinical importance of this remains unclear; further research is required to establish whether this results in harm.

Ultraviolet filters found within chemical sunscreens may be harmful to the environment.

In Canada, more than 80 000 cases of skin cancer are diagnosed every year. 1 Because exposure to ultraviolet radiation is estimated to be associated with 80%–90% of skin cancers, the use of sunscreen — which blocks ultraviolet radiation — is promoted as an important means of preventing skin cancers, 2 , 3 as well as sunburn and skin photoaging (see definitions in Appendix 1, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.201085/tab-related-content ). Use of sunscreen has been shown to reduce the incidence of both melanoma and nonmelanoma skin cancers. 4 , 5 Both the Canadian Dermatology Association and the American Academy of Dermatology recommend the use of sunscreen for the prevention of skin cancer. 6 , 7 Yet, since the development of the first commercial sunscreen in 1928, questions regarding the safety and efficacy of sunscreen have been raised, and more recently, the impact of sunscreens on the environment has become a cause for concern. We summarize evidence related to the effectiveness and harms of sunscreen to help physicians counsel their patients ( Box 1 ).

Evidence used in this review

We conducted a targeted search of MEDLINE using a combination of the search terms “sunscreen,” “skin cancer,” “melanoma,” “squamous cell carcinoma,” “basal cell carcinoma,” “photoaging,” “safety” and “environment” to identify studies published from 1984 to 2020. We particularly sought randomized controlled trials, systematic reviews and meta-analyses relevant to this article’s clinical questions. We also identified relevant review articles, basic science publications and institutional guidelines. We supplemented our search with literature from our own collections.

• How do sunscreens work?

Sunscreens contain chemical (organic) or physical (inorganic) compounds that act to block ultraviolet radiation, which is light with wavelengths shorter than visible light (subdivided into ultraviolet A [UVA]1, UVA2, ultraviolet B [UVB] and ultraviolet C [UVC]), as shown in Figure 1 . Generally, the shorter the wavelength, the greater the potential for light radiation to cause biological damage. Sunscreen filters are active against UVA1, UVA2 and UVB radiation. Chemical filters, such as oxybenzone, avobenzone, octocrylene and ecamsule, are aromatic compounds that absorb high-intensity ultraviolet radiation, resulting in excitation to higher energy states. When these molecules return to their ground states, the result is conversion of the absorbed energy into lower-energy wavelengths, such as infrared radiation (i.e., heat). 8

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Schematic representation of the electromagnetic spectrum of light, emphasizing ultraviolet radiation (UVR) frequencies and their effect on human skin. Generally, the shorter the wavelength of radiation, the greater the potential for biological damage. Note: UVA = ultraviolet A, UVB = ultraviolet B, UVC = ultraviolet C. Sunscreen filters are active against UVA1, UVA2 and UVB radiation.

Physical sunscreen filters, such as titanium dioxide and zinc oxide, reflect or refract ultraviolet radiation away from the skin; however, experimental studies have shown that when particle sizes are very small, as in micronized sunscreens, the mechanism of action is similar to that of chemical filters. More specifically, micronized zinc oxide and titanium dioxide behave as semiconductor metals, which absorb ultraviolet light throughout most of the electromagnetic spectrum. 9 The sunscreen ingredients that are currently approved by Health Canada are listed in Table 1 . 10

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Sunscreen ingredients approved by Health Canada 10

• What is the effectiveness of sunscreens in preventing photoaging and skin cancer?

Evidence from observational studies, 11 a large randomized controlled trial (RCT) 12 and smaller, nonrandomized experimental studies 13 – 15 support the effectiveness of sunscreens in preventing the signs of photoaging, including wrinkles, telangiectasia and pigmentary alterations induced by ultraviolet radiation. 11 – 15 Despite the challenges of studying skin cancer, owing to its multifactorial pathogenesis and long lead time, the following evidence supports the use of sunscreen in the prevention of skin cancer.

Experimental studies from the 1980s and 1990s showed that sunscreens protect against cell damage consistent with carcinogenesis in animal models. 16 , 17 A well-conducted community-based 4.5-year RCT of 1621 adult Australians, with follow-up for more than a decade, found a 40% lower incidence of squamous cell carcinomas among participants randomized to recommended daily sunscreen compared with participants assigned to use sunscreen on a discretionary basis (rate ratio 0.61, 95% confidence interval [CI] 0.46 to 0.81). 4 , 18 However, the incidence of basal cell carcinomas was not significantly reduced, possibly owing to the protracted pathogenesis of basal cell carcinomas. 18 Almost 15 years after the completion of the study, participants who used sunscreen daily throughout the 4.5-year study period showed a significantly reduced risk of invasive melanoma (hazard ratio [HR] 0.27, 95% CI 0.08 to −0.97), although very few invasive melanomas were noted, given the long lead time for this type of tumour. 5 A predefined subgroup analysis in this trial confirmed that regular use of sunscreen over a 4.5-year period can arrest signs of skin aging caused by photodamage. 12 Another large Australian RCT showed a significantly reduced rate of development of actinic keratoses (a precursor to squamous cell carcinoma) among participants randomized to regular use of sunscreen, compared with controls who used a nonactive base cream over 1 summer season (rate ratio 0.62, 95% CI 0.54 to −0.71). 19

In organ transplant recipients, a population at high risk of morbidity and death from skin cancer, a prospective single-centre study of 120 matched patients showed that the use of sun protection factor (SPF) 50 sunscreen over 24 months reduced the development of actinic keratoses, squamous cell carcinomas and, to a lesser extent, basal cell carcinomas. 20 Recent meta-analyses have not supported the findings of these RCTs, finding no significant effectiveness of sunscreen for preventing either melanoma or nonmelanoma skin cancers. 21 , 22 However, these meta-analyses included studies with retrospective designs with methodological inconsistencies among studies, and 1 included studies that used only UVB filters (rather than broad-spectrum sunscreens). 21 Overall, the highest-quality evidence available suggests that sunscreens do prevent skin cancer.

• Who should use sunscreen?

The American Academy of Dermatology recommends regular sunscreen use with an SPF of 30 or higher for people of all skin types, 23 although skin cancers are far more prevalent in White individuals than people with darker skin. 24 There have been no studies to assess the effectiveness of regular sunscreen use in reducing the risk of skin cancers among people who are not White.

For children older than 6 months, as well as adults, the Canadian Dermatology Association recommends the use of broad-spectrum sunscreens with an SPF of 30 or greater. 7 Split-face studies have shown that sunscreens with an SPF of 100 are superior to sunscreens with an SPF of 50 for preventing sunburns under actual use conditions, in both a beach setting 25 and a high-altitude skiing setting. 26

Health Canada does not recommend the use of sunscreen for children younger than 6 months because of the theoretical risk of increased absorption of sunscreen ingredients as a result of higher body surface-to-volume ratios and thinner epidermis. 27 The mainstays of sun safety in infants include sun avoidance and protective clothing. 28 If sunscreen is used in infants, experts suggest washing it off as soon as it is no longer needed, 29 and favouring physical sunscreens over chemical varieties.

• How should sunscreen be applied?

Observational studies have shown that consumers typically underapply sunscreen, with standard use ranging between 20% and 50% of the recommended application. 30 – 32 However, using sunscreens with higher SPFs may compensate for underapplication. 26 For example, when a sunscreen with an SPF of 50 is applied under real-world conditions, the sunscreen may provide an SPF of only 25.

A 2015 Canadian consensus meeting agreed that the wording “apply sunscreen generously” was most appropriate, given differences in body habitus of the public. 33 Figure 2 offers a rough estimate of the quantities of sunscreen that should be applied by a person of average height and build, based on advice from the Canadian Cancer Society and the American Academy of Dermatology.

Visual aid to guide the correct application of sunscreen for a person of average height and body habitus, based on advice from the Canadian Cancer Society and the American Academy of Dermatology.

Although product labelling often suggests that sunscreens should be applied 15 to 30 minutes before going outdoors, 34 in a recent study, immediate protection against ultraviolet radiation occurred after sunscreen application, although protection after water exposure was not examined. 35 Therefore, it may be prudent to wait 15 to 30 minutes if water resistance is required.

Recent experimental studies have shown that sunscreen remains on the skin at the desired SPF for as long as 8 hours after a single application, 35 – 38 suggesting that historical advice to reapply sunscreen every 2–3 hours need not be followed even when individuals are physically active. However, reapplication is suggested when the likelihood of sunscreen having been removed is high, such as after sweating, water immersion, friction from clothing and exfoliation from sand. 39 – 41 When swimming or sweating are anticipated, water-resistant sunscreens should be used. 40

Spray-on sunscreens are less desirable than cream-based ones, for several reasons. Wind can disperse the sunscreen, resulting in inadequate application. Moreover, because spray-on sunscreens are often fast drying, and sometimes not clearly visible once sprayed onto the skin, it is difficult to determine whether application was homogeneous. 42 Aerosolized sunscreens are also flammable, and several incidences of combustion on the skin have been reported after exposure to open flames, even after the sunscreen has been allowed to dry. Finally, the potential risks associated with inhalation of aerosolized sunscreens have not been adequately studied. 43

• What are the key safety concerns?

Skin reactions

The most common reported adverse reactions to sunscreens include subjective irritation (e.g., stinging and burning) without a rash, irritant contact dermatitis and comedogenicity. Rarely, chemical sunscreen ingredients may also cause allergic contact dermatitis and photoallergic contact dermatitis, with the most commonly implicated allergenic ingredients being octocrylene, oxybenzone and octyl methoxycinnamate. 44

Absorption of sunscreen

In 2019, a small RCT with 24 participants, sponsored by the United States Food and Drug Administration, showed systemic absorption of 4 sunscreen ingredients: oxybenzone, avobenzone, octocrylene and ecamsule. 45 When applied under maximal use conditions, over 4 consecutive days, blood levels for these compounds exceeded those recommended by US Food and Drug Administration guidelines. 45 Moreover, the investigators noted long half-lives for each of these ingredients, suggesting that regular sunscreen use may lead to accumulation within the body. 46 A follow-up study confirmed these findings. 47 However, most people use far less than this volume of sunscreen and, despite their findings, the study investigators encouraged the use of sunscreen given its known protective effects, as the clinical importance of absorption of these ingredients is not yet known. Further research is needed to determine whether there are any potential health sequelae from absorption of sunscreen ingredients.

In contrast to chemical sunscreen ingredients, physical sunscreens are not systemically absorbed. An in-vitro study found that less than 0.03% of zinc nanoparticles penetrated the uppermost layer of the stratum corneum, and no particles were detected in the lower stratum corneum. 48 Physical sunscreens historically were less cosmetically appealing than chemical sunscreens, leaving a white residue on the skin, potentially leading to underapplication. Advances in formulation and micronization of physical ultraviolet radiation filters has led to more cosmetically acceptable physical sunscreens. 49

Endocrine effects

Low-quality evidence has led to concerns about possible estrogenic and antiandrogenic effects of chemical sunscreens. Although a recent meta-analysis found that oxybenzone is associated with reproductive adverse effects in fish, the summarized literature was nonuniform and the results therefore uninformative. 50 Among human research participants, a prospective study noted reduced fecundity when men were exposed to benzophenone-2 and 4-hydroxybenzophenone, but the findings could be explained by study confounding. 51 One systemic review, which evaluated both animal and human studies, found that high levels of oxybenzone exposure during pregnancy were associated with decreased gestational age in male neonates and decreased birthweight in female neonates. 50 However, high heterogeneity limited the usefulness of the study findings. 50

• How do sunscreens affect the environment?

Some recent studies have reported that chemical sunscreen ingredients are detectable in various water sources 52 , 53 and may persist despite waste-water treatment processing. 54 An additional recent concern is the detection of sunscreen filters in the tissues of various fish species, raising the possibility of bioaccumulation and biomagnification. 55

The effects of sunscreen ingredients on coral reefs are a current focus of scientific investigation. In-vitro studies have shown that oxybenzone affects coral reef larvae 56 and may be implicated in coral reef bleaching. However, possible confounding variables include increased ocean salinity and temperature associated with global warming. 55 These preliminary studies have prompted the banning of oxybenzone and octinoxate in some jurisdictions. 57

• What additional photoprotective measures may be used?

Sunscreen is only one part of a comprehensive photoprotection strategy. It is important to counsel patients regarding behaviours for avoiding ultraviolet radiation, including the use of wide-brimmed hats, eye protection (e.g., “wrap-around” sunglasses with ultraviolet radiation protection) and seeking shade when the ultraviolet index is above 3 (usually 11 am–3 pm, April to September in Canada). 33 Typically, thicker clothing with tighter weave fabrics — such as polyester and cotton, or nylon and elastane (i.e., Spandex, Lycra) — and darker colours offer greater protection. 58 , 59 Clothing has been designed for sun protection with an ultraviolet protection factor (UPF) up to 50. 28 All clothing will become less photoprotective if it is wet or stretched. 59

• Potential new sunscreen technologies

Topical photolyases and antioxidants (vitamin C, vitamin E, selenium and polyphenols found within green tea extracts) are emerging as potential agents of topical and nontopical photoprotection. Antioxidants cannot yet be stabilized within sunscreen formulations to remain biologically active. Studies have established that sunscreens that claim antioxidant activity have little to no actual antioxidant activity. 60 – 62

Photoprotective agents taken orally, such as niacinamide and Polypodium leucotomos extract, which is derived from a fern native to Central and South America, are used as agents for prevention of photodamage. There is evidence from small RCTs that P. leucotomos extract increases the minimal erythema dose of sun exposure without significant adverse effects, and is helpful for dermatologic diseases induced by ultraviolet radiation, such as polymorphous light eruption and solar urticaria. 63 – 65

Nicotinamide, also known as niacinamide, is the active amide form of niacin (vitamin B3). However, unlike niacin, it does not cause cutaneous flushing. Nicotinamide has been shown in early studies to enhance DNA repair and decrease the formation of cyclobutene pyrimidine dimers in human keratocytes. 62 In one phase III RCT, which has not been replicated, nicotinamide 500 mg twice daily was associated with a decreased rate of development of both actinic keratoses and nonmelanoma skin cancers over a 12-month period. 66 However, the skin cancers that did occur tended to be high-grade malignancies.

Exposure to ultraviolet radiation is directly harmful and has been associated with the development of skin cancers, which are common in Canada. High-quality evidence has shown that sunscreen reduces the risk of developing both melanoma and nonmelanoma skin cancer. Therefore, physicians should counsel patients on photoprotection strategies, including avoiding midday sun, seeking shade and wearing protective clothing, as well as using sunscreen if sun exposure cannot be avoided. Presently, the Canadian Dermatology Association recommends the use of a broad-spectrum sunscreen with an SPF of at least 30 for people older than 6 months, for photoprotection. Low-quality evidence has shown that some chemical sunscreen ingredients are systemically absorbed and may be contributing to environmental damage; people who are concerned may consider using physical sunscreens as an alternative. Research on the safety and efficacy of established sunscreens and novel agents is ongoing.

Competing interests: Toni Burbidge reports receiving honoraria from AbbVie, Celgene, Janssen, Leo Pharmaceuticals and Lilly. No other competing interests were declared.

This article has been peer reviewed.

Contributors: All of the authors contributed to the conception and design of the work, and the acquisition, analysis and interpretation of data. All of the authors drafted the manuscript, revised it critically for important intellectual content, gave final approval of the version to be published and agreed to be accountable for all aspects of the work.

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September 6, 2023

What Are the Best and Safest Sunscreens?

What dermatologists say about sun sensitivity, cancer risk and the products they use for sun protection

By Sam Jones

Meeko Media/Getty Images

Sunscreen is one of our best defenses against the sun’s harmful ultraviolet rays, but over the past few years it has been in the news for potential health concerns.

In May 2021 Valisure —an independent company focused on pharmaceutical transparency— detected benzene contamination in 78 sunscreen and after-sun care products from a number of brands. Benzene is a known carcinogen, meaning it can cause cancer , and is linked to a number of other short- and long-term health problems. Many product recalls followed, particularly of aerosol sunscreens .

But approved sunscreen ingredients also made headlines that year, following a statement from the Food and Drug Administration that said many of them cannot be considered safe, based on either poor safety data or a lack of data altogether.

Ditching sunscreen altogether isn’t a good option: UV rays from the sun are known to cause skin cancer and premature skin aging. For instance, several studies have shown that UV exposure increases a person’s risk of developing melanoma , an aggressive form of skin cancer that more than 90,000 people in the U.S. are expected to be diagnosed with each year. So whenever you head outdoors, here’s what to know about the different categories of sunscreen available, what active ingredients could be of concern, what dermatologists recommend and use themselves and why there seem to be so many more sunscreen options outside the U.S.

What types of sunscreen are on the market?

Sunscreens are broadly divided into two categories: mineral and chemical. Active ingredients in chemical sunscreen are carbon-based and include compounds such as avobenzone and oxybenzone. Mineral sunscreens are not carbon-based and include two compounds: titanium dioxide and zinc oxide. Both mineral and chemical sunscreens protect wearers from UV rays. Although mineral sunscreens are often described as solely reflecting UV light and chemical sunscreens are frequently described as absorbing it, mineral sunscreens do both .

Joshua Zeichner , director of cosmetic and clinical research in dermatology at Mount Sinai Hospital in New York City , says that chemical sunscreens typically offer superior aesthetics, compared with mineral sunscreens, which can feel a bit heavier and sometimes leave the skin white and pasty. Chemical sunscreen also allows for a higher SPF, or sun protection factor , which is a measure of how much UV radiation is needed to cause a sunburn on sunscreen-coated skin versus unprotected skin. A higher SPF generally means more UV protection, but after about SPF 30, the differences in protection are more modest . “The reason that you don't see ultrahigh SPF levels with mineral sunscreens is because it would require so much of the mineral that it would be like applying a zinc paste onto the skin,” Zeichner says.

“Chemical sunscreens are generally more common [and] cheaper and can be easier to rub into the skin,” says Shreya Patel , a dermatologist at Affiliated Dermatologists & Dermatologic Surgeons PA’s office in Morristown, N.J. But for people with sensitive skin and conditions such as eczema or psoriasis, mineral sunscreens can be less irritating. “Certain chemical sunscreens are typically associated with skin allergies or irritation, including those with oxybenzone, cinnamates and octocrylene,” Patel says. “We recommend using mineral sunscreens in these cases, as these products rarely cause skin reactions.”

Should you avoid certain sunscreen ingredients?

In the U.S., the over-the-counter monograph for sunscreen products—a document that defines the safety, effectiveness and labeling of active ingredients— lists 16 such ingredients that are categorized as GRASE (generally recognized as safe and effective) and therefore do not require FDA approval to be used in a new product. But on September 24, 2021, the agency put forth a proposal that would amend the monograph .

The FDA proposed that chemical sunscreens that contain aminobenzoic acid (PABA) and trolamine salicylate are not GRASE. PABA’s risks include severe sun sensitivity, and trolamine salicylate can cause serious bleeding, vomiting and— in extreme circumstances — death . “These ingredients don’t need to be removed from the market until we finalize our proposal,” says Theresa Michele, director of the Office of Nonprescription Drugs at the FDA . But currently “there are actually no marketed sunscreen products containing these two ingredients.”

Citing a need for more data in its September 2021 document, the agency also proposed “not GRASE” status for the chemical ingredients oxybenzone, avobenzone, cinoxate, dioxybenzone, ensulizole, homosalate, meradimate, octinoxate, octisalate, octocrylene, padimate O and sulisobenzone. Clinical trials led by FDA scientists have shown that many of these active ingredients are absorbed into the bloodstream at levels above the concentration threshold the agency has set for determining potential cancer risk. But it’s unclear whether having those active ingredients in the bloodstream is dangerous. “Insufficient data does not mean that’s a conclusion by us that they’re unsafe,” Michele says. “It just means we’re requesting additional data.”

In 2021 bans on the sale of sunscreens containing oxybenzone or octinoxate went into effect in Hawaii and Key West, Fla., but not because of human health—the ruling followed years of laboratory studies that showed the compounds are harmful to corals and other marine life.

The FDA’s September 2021 proposal included keeping the status of the two remaining active ingredients—zinc oxide and titanium dioxide, the two compounds used in mineral sunscreens—as GRASE. “And because of the statement that the mineral sunscreens are considered safe and effective, the chemical sunscreens now have a bad reputation,” Zeichner says. But “as a dermatologist, I personally do recommend chemical sunscreens on a daily basis, and I use them on myself and on my family.”

What do dermatologists recommend?

“Ultimately the best product is the one that you’ll actually use,” Zeichner says. He adds that it is important to look for a product with at least SPF 30 that says “broad spectrum” because that means it protects against both ultraviolet A and B (UVA and UVB) rays. “My personal opinion is to choose a product that has the highest SPF level possible,” Zeichner says, because people rarely put enough of it on or reapply it frequently, and the SPF will be quickly diluted if too thin a layer is applied or if the sunscreen is sweat off.

“I recommend my patients use whatever sunscreen they feel comfortable applying to their skin and that they will use regularly,” says dermatologist Samer Jaber of Washington Square Dermatology in New York City . “I personally prefer the mineral sunscreens with zinc oxide or titanium dioxide as they are less irritating. But as long as my patients use sunscreen, I am happy.”

Patel also defers to her patients’ preference, as long as the sunscreen is broad-spectrum and has an SPF of at least 30. “The most important thing is to use sunscreen every day on at least all the sun-exposed areas of the body—including the face, ears, neck and hands,” she says.

Wearing protective clothing, finding shade and avoiding peak sun hours around midday are also effective ways to protect against sun damage.

Why are there many more sunscreen options outside the U.S.?

“To qualify as a drug in the U.S., something has to make a drug claim, which sunscreens do ,” Michele says. They claim to help prevent sunburn or to decrease the risks of skin cancer and early skin aging caused by the sun.

“Because sunscreens are considered drugs in the U.S., they are tightly regulated and require extensive testing to be approved,” Jaber says. This means fewer available active ingredients for sunscreen manufacturers to work with in the U.S., compared with other countries, including the U.K., where sunscreens are considered cosmetics and don’t undergo the same extensive regulation.

In the U.S., the last approval for an active sunscreen ingredient was in 1999 , “whereas in Europe and Asia, there have been numerous new sunscreen ingredients approved that offer better UVA protection, are longer lasting [and] less greasy and have a better texture, which makes them more likely to be applied,” Jaber says. Regulations are not necessarily lacking in other countries—in the European Union, for example, sunscreens still need to be approved by the European Commission following assessment by the Scientific Committee for Consumer Safety . And in Japan, the Japanese Ministry of Health, Labor and Welfare regulates cosmetics under the Pharmaceutical Affairs Law. But comparatively, FDA requests for additional safety data have frustrated many , and even led to the creation of the Public Access to SunScreens (PASS) Coalition , an alliance between public health organizations, sunscreen manufacturers and others focused on increasing access to more effective sunscreens. That includes active ingredients that offer better UVA protection.

Longer-wavelength UVA rays penetrate deeper into the skin than shorter-wavelength UVB rays , although both types are known to cause skin cancer. It would be an important step forward if U.S. sunscreens could provide better UVA protection, Zeichner says. “I think we’re all eagerly awaiting the FDA to allow newer ingredients to be incorporated into U.S. sunscreens,” he says. “And I know that a lot of the cosmetic companies are waiting for that as well. They have new formulations waiting in the wings.”

“The cost of testing can be very expensive and thus discourage international brands from obtaining approval in the U.S.,” Patel says. But, she adds, there is an upside to the stricter regulation. “This also helps ensure that the active ingredients the population is exposed to are safe and protective,” she says.

“We continue to invite sunscreen manufacturers to submit data showing that sunscreens that aren’t yet on the market here are generally recognized as safe and effective,” Michele says. “So far, we haven’t gotten that data.”

How Sunscreen Became Controversial

W earing sunscreen every day sounds like a no-brainer piece of health advice. Research suggests regular sunscreen use reduces the risk of potentially deadly skin cancers like melanoma, as well as visible signs of skin aging. The American Academy of Dermatology states its position in no uncertain terms: Everyone should wear sunscreen every day they’ll be outside.

But there’s been mounting pushback to that idea in recent years, mainly due to concerns about the health risks associated with chemicals in many popular sunscreens. These days, it’s not hard to find sources—including influencers , marketers , consumer-protection groups , and scientists —raising questions about the safety and necessity of sunscreen.

Here’s how sunscreen became controversial—and how to interpret safety concerns.

Why is there skepticism about sunscreen?

There are two main types of sunscreens : chemical and mineral formulas. The former use organic filters to absorb potentially harmful UV rays. About a dozen of these filters are commonly used in the U.S., including oxybenzone, octinoxate, avobenzone, homosalate, and octocrylene. Meanwhile, mineral formulas create a physical barrier against the sun’s rays using inorganic filters like zinc and titanium dioxide. Much of the concern about sunscreen centers on the chemical formulas.

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In 2019, the U.S. Food and Drug Administration (FDA) requested additional safety data from sunscreen manufacturers. At the time, the agency said zinc oxide and titanium dioxide should be “generally recognized as safe and effective,” while PABA and trolamine salicylate, two lesser-used chemical filters, should not. The agency said it didn’t have adequate evidence to determine whether other chemical filters could be considered safe and effective. That doesn’t necessarily mean other chemical filters are unsafe, only that regulators wanted more data about them—but the FDA’s request kicked off a flurry of headlines about the potential risks of common sunscreens.

Then, in 2019 and 2020, FDA researchers released two studies that reached the same conclusion: Common sunscreen chemicals, including oxybenzone, can pass through the skin and into the bloodstream. That finding also sparked alarm among some consumers, even though the researchers encouraged people to keep wearing sunscreen.

Adding fuel to the fire, a lab in 2021 found the carcinogen benzene in many suncare products, and big brands including Coppertone issued recalls. The same year, Hawaii began enforcing a sales ban on sunscreens containing oxybenzone and octinoxate, citing harm to coral reefs. Other localities have enacted similar policies , raising concern about the environmental as well as physiological effects of sunscreen.

Are the concerns about sunscreen legit?

Researchers have found that frequent sunscreen use is linked to higher oxybenzone levels in urine. But studies haven’t concretely proven the absorption of UV filters is dangerous to humans.

“The question is, is that significant? Does it mean anything?” says Dr. Victoria Werth, a dermatologist at Penn Medicine who is also board-certified in internal medicine. “Just because you can measure it doesn’t mean it’s a problem.”

There are some concerning signals. Some studies have found links between sunscreen chemicals, namely oxybenzone, and changes in hormone , kidney , and reproductive function , and animal research has raised questions about whether oxybenzone may increase cancer risk.

But “it’s really hard to say, ‘Would that really happen in the human body?’” says Dr. Archana Sadhu, an endocrinologist at Houston Methodist Hospital. Animal and laboratory research doesn’t always translate to real-life conditions. Animals’ bodies work differently than humans’, and real people may not use sunscreen at dosages or frequencies comparable to those in lab studies. (European scientists have, however, recommended capping oxybenzone and homosalate concentrations at levels below those used in U.S. products.)

Similarly, much of the research on sunscreen and coral damage has occurred in the laboratory, rather than under real-world conditions, leading some researchers to question whether sunscreen is actually damaging ocean life enough to necessitate bans on certain formulas.

Should I still wear sunscreen?

The FDA , U.S. Centers for Disease Control and Prevention , and many medical associations all recommend using sunscreen. An estimated one in five people in the U.S. will develop skin cancer during their lifetimes, and more than 7,000 people in the U.S. die from melanoma every year. Sunscreen can help prevent those outcomes.

Ultimately, Sadhu says, most people are better off reaping that known benefit, rather than swearing off sunscreen due to unclear risks. Plus, she notes, people are exposed to potentially harmful chemicals constantly , whether in beauty products, plastics, food and water, or the environment. “It’s not like you’re making this one switch and all of a sudden you’ve made your risk zero,” Sadhu says. People who are worried, she says, would likely be better off ditching cosmetics—which typically have no health-related purpose—than sunscreen.

Physicians often recommend mineral-based products to people who are concerned about sunscreen safety. There is some inconclusive evidence about whether titanium dioxide particles can be absorbed into the body or cause health problems , but mineral sunscreens are generally considered less-risky than chemical-based products.

The consumer watchdog Environmental Working Group (EWG) evaluates the safety and efficacy of sunscreen formulas , and the “vast majority” of products that receive its top scores are mineral formulas, says David Andrews, one of EWG’s senior scientists working on sunscreen. (Since last year, EWG has tracked a 50% drop in the number of non-mineral sunscreens that use oxybenzone, a shift Andrews thinks is driven largely by safety and environmental concerns.)

Andrews agrees that consumers shouldn’t stop wearing sunscreen, but warns the products can provide a “false sense of security.” Some consumers overestimate the efficacy of sunscreen, staying outdoors longer than they otherwise would and increasing their overall sun exposure. Instead of relying solely on sunscreen, Andrews says, people should wear protective clothing, seek out shade, and limit their time in the sun.

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Write to Jamie Ducharme at [email protected]

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Use of sunscreen and risk of melanoma and non-melanoma skin cancer: a systematic review and meta-analysis

Affiliations.

• 1 Physiotherapy and Dermatology Clinic, Postgraduate Program in Public Health, Faculty of Medicine, Federal University of Rio Grande, Rio Grande-RS, Brazil.
• 2 Faculty of Medicine, Federal University of Rio Grande, Rio Grande-RS, Brazil.
• 3 Postgraduate Program in Public Health, Faculty of Medicine, Federal University of Rio Grande, Rio Grande-RS, Brazil.
• 4 Postgraduate Program in Public Health and Postgraduate Program in Health Sciences, Faculty of Medicine, Federal University of Rio Grande, Rio Grande-RS, Brazil.
• PMID: 29620003
• DOI: 10.1684/ejd.2018.3251

The use of sunscreen is a key component of public health campaigns for skin cancer prevention, but epidemiological studies have raised doubts on its effectiveness in the general population. This systematic review and meta-analysis aimed to assess the association between risk of skin cancer and sunscreen use. We searched PubMed, BIREME and Google Scholar from inception to May 17, 2017, to identify observational studies and controlled trials. We used a random-effects model for conventional and cumulative meta-analyses. We included 29 studies (25 case-control, two cohort, one cross-sectional, and one controlled trial) involving 313,717 participants (10,670 cases). The overall meta-analysis did not show a significant association between skin cancer and sunscreen use (odds ratio (OR) = 1.08; 95% CI: 0.91-1.28, I 2 = 89.4%). Neither melanoma (25 studies; 9,813 cases) nor non-melanoma skin cancer (five studies; 857 cases) were associated with sunscreen use, with a pooled OR (95% CI) of 1.10 (0.92-1.33) and 0.99 (0.62-1.57), respectively. The cumulative evidence before the 1980s showed a relatively strong positive association between melanoma and sunscreen use (cumulative OR: 2.35; 95% CI: 1.66-3.33). The strength of the association between risk of skin cancer and sunscreen use has constantly decreased since the early 1980s, and the association was no longer statistically significant from the early 1990s. While the current evidence suggests no increased risk of skin cancer related to sunscreen use, this systematic review does not confirm the expected protective benefits of sunscreen against skin cancer in the general population.

Keywords: melanoma; meta-analysis; skin cancer; sunscreen; systematic review.

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The Banned Sunscreen Ingredients and Their Impact on Human Health: A Systematic Review

Susie suh , ba, christine pham , bs, janellen smith , md, natasha atanaskova mesinkovska , md, phd.

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Corresponding Author Natasha Atanaskova Mesinkovska, MD, PhD, Dermatology Clinical Research Center, University of California, Irvine, 843 Health Sciences Road, Irvine, CA 92697, Phone: (949) 824-1732, Fax: (949) 824-8954, [email protected]

Issue date 2020 Sep.

Background:

Recent evidence of high systemic absorption of sunscreen ingredients has raised concerns regarding the safety of sunscreen products. Oxybenzone (BP-3) and octinoxate (OMC), two common sunscreen ingredients, were recently banned in Key West and Hawaii due to their toxic effects on marine ecosystems. Their impact on human health requires a careful assessment.

To summarize the current evidence on the association between the systemic level of BP-3 or OMC and its health impact.

A primary literature search was conducted using PubMed database in February 2019.

There are 29 studies that address the impact of these ingredients on human health. Studies show that elevated systemic level of BP-3 has no adverse effect on male and female fertility, female reproductive hormone level, adiposity, fetal growth, child’s neurodevelopment and sexual maturation. However, the association of BP-3 level on thyroid hormone, testosterone level, kidney function and pubertal timing has been reported and prompts further investigations to validate a true association. The systemic absorption of OMC has no reported effect on thyroid and reproductive hormone levels.

Conclusions:

Current evidence is not sufficient to support the causal relationship between the elevated systemic level of BP-3 or OMC and adverse health outcomes. There are either contradictory findings among different studies or insufficient number of studies to corroborate the observed association. To accurately evaluate the long-term risk of exposure to BP-3 and OMC from sunscreen, a well-designed longitudinal randomized controlled trial needs to be conducted.

Keywords: benzophenone-3, oxybenzone, sunscreen, octyl methoxycinnamate, octinoxate, toxicity, endocrine, reproductive, fertility, endocrine disrupting compounds, EDC, systemic absorption

1. Introduction

The concern for safety and effectiveness of sunscreen ingredients has been heightened after recent evidence of their measurable systemic absorption following topical application 1 , 2 . Indeed, the US Food and Drug Administration (FDA) emphasized the importance of the safety assessment on all sunscreen ingredients with systemic absorption greater than 0.5 ng/mL 3 . In the recent randomized controlled trial, 4 out of 4 tested sunscreen ingredients were found in the subjects’ blood at concentrations exceeding the FDA threshold for waiving toxicology assessment, thereby raising concerns among sunscreen users 1 . In fact, concerns regarding the safety of sunscreen ingredients were growing even before the study was published. In 2018 and 2019, the state of Hawaii and Key West, Florida banned the sale of sunscreen containing oxybenzone (BP-3) or octinoxate (OMC) due to their detrimental threat to the marine ecosystems 4 - 6 . Their toxic effects on other species has alarmed the general public about their potential to impact human health when applied to human skin 7 .

BP-3 and OMC are two common sunscreen ingredients that are also known to have endocrine-disrupting potential 8 . While they are mainly used as UV filter in sunscreens, they are also prevalent in air, drinking water, cosmetics, fragrances and plastic packagings, providing additional routes of exposure to humans 9 . Numerous studies have shown that they can penetrate through the skin and enter the systemic circulation 1 , 10 - 15 . They have been detected in urine, blood, semen, and even amniotic fluid and breast milk, thereby raising concerns about their negative consequences on fetal development as well as other organ systems 9 , 16 . However, whether the presence of these ingredients in systemic circulation poses risks to human health is unclear. To answer whether systemic absorption of sunscreen poses risks to human health, further investigation is needed.

In this review, we evaluated current evidence on the association between the systemic levels of BP-3 and OMC in humans, and altered health outcomes and fetal development to help provide an insight into the potential clinical significance of the sunscreens’ systemic absorption.

A literature search was conducted for all relevant publications in the Pubmed using the following search term: (benzophenone-3 OR oxybenzone OR octinoxate OR octyl methoxycinnamate) AND (endocrine OR reproductive OR kidney OR liver OR cancer OR brain OR hormone OR skin OR hair OR gastrointestinal OR defect OR embryo OR pregnant OR nervous system OR autoimmune disease) AND (animal OR mice OR rat OR rabbit OR human). All articles were searched from January 1, 1979 to February 22, 2019. A total of 423 studies were retrieved, and two independent reviewers screened all titles and abstracts in accordance to the Preferred Reporting System for Systematic Reviews and Meta-Analyses (PRISMA) guidelines ( Figure 1 ). The following exclusion criteria were applied: 1) non-evidence-based studies including review articles, letters and commentaries; 2) in vitro studies using cultured cell or tissue; 3) animal studies using non-mammalian species such as insects and amphibians; 4) studies written in languages other than English; 5) studies that do not focus on physiological outcome. The following inclusion criteria were applied: 1) studies conducted on either humans or mammalian species (e.g. mice, rats); 2) studies that included univariate analysis between BP-3 (or OMC) level and physiological outcome.

Figure 1. PRISMA Diagram.

Process of inclusion of studies

3.1. Selection of Studies

29 studies met our criteria. 16 studies evaluated the association between the systemic levels of BP-3 (n=16) or OMC (n=2, also included in BP-3) and various outcomes in organ systems, whereas 13 studies evaluated the association between the prenatal systemic levels of BP-3 (n=13) and outcomes in child development ( Table 1 ). We quantified the number of supporting and refuting evidences into Tables 2 and 3 .

Human studies on the association between the systemic levels of oxybenzone (BP-3)/octinoxate (OMC) and health outcome

All subjects are adults unless otherwise stated.

Abbreviations: LOE, Level of Evidence; M, male; F, female; y/o, year-old; T3, Total triiodothyronine; T4, Total thyroxine; TSH, Thyroid Stimulating Hormone; FT3, Free triiodothyronine; FT4, Free thyroxine; QD, once a day; 4-MBC, 4-Methylbenzylidene camphor; QD, once a day; FSH, Follicle Stimulating Hormone; LH, Leutinizing Hormone; IQR, Interquartile Range; SHBG, sex hormone-binding globulin; AOR, adjusted odds ratio

Number of human studies about the association between urinary concentration of oxybenzone (BP-3) or octinoxate (OMC) and the physiological outcomes. n=16 (duplicate excluded)

In parenthesis, ↓ indicates a negative correlation with elevated BP-3 level. ↑ indicates a positive correlation with elevated BP-3 level.

The results are from the same paper that is also included in BP-3 column.

Number of human studies about the association between maternal prenatal urinary concentration of oxybenzone (BP-3) or octinoxate (OMC) and the target effects in child. n=13 (duplicate excluded)

3.2. Oxybenzone

3.2.1. effects on organ systems.

We have found 29 studies that assess the impact of high systemic level of BP-3 on endocrine, reproductive, metabolic, renal systems and neonatal development during pregnancy ( Table 1 ). The effect on thyroid hormone levels was most extensively studied (n=5) most likely due to its endocrine disrupting potential shown in animal studies. Despite the amount of evidence, the association between elevated systemic level of BP-3 and thyroid hormone levels in humans is still inconclusive, because the observed association from each study was not consistent throughout all other studies. Two studies showed an association of higher urinary BP-3 concentrations with decreased thyroid hormones, yet one study showed an inverse association with T4, and another showed the association with T3 only 17 , 18 . Interestingly, the two most recent studies with a cohort of 1560 and 439 demonstrated no statistically significant association (p<0.05) between urinary BP-3 concentration and thyroid hormone levels, disputing the results from two previous studies 19 , 20 . Of the five studies referenced above, only one study assessed the thyroid hormone level after sunscreen application. In this single-blinded clinical trial, 32 volunteers applied cream formulated with 10% of three active ingredients in sunscreen (OMC, BP-3, and 4-methylbenzylcathinone) for one week, and the plasma thyroid levels before and after treatment were measured 21 . No biologically significant effects on thyroid hormone levels were observed after one week, indicating that the maximum allowable concentration of BP-3 in sunscreen was not capable of disturbing the homeostasis of thyroid hormones, at least during the short duration of the study.

The effect of BP-3 concentration on fertility was the second most common potential outcome studied (n=4 studies) 22 - 25 . All four studies demonstrated that there was no association between BP-3 exposure and fertility although different parameters were used for measuring fertility, which included semen analysis, the number of menstrual cycles required to achieve pregnancy, and a hazard ratio for spontaneous abortion.

The estrogenic and anti-androgenic activities of BP-3 have frequently been reported in in vitro and animal studies, but its impact on human reproductive endocrine systems has not been addressed in great detail. We found four studies that investigated the effect of elevated systemic level of BP-3 on reproductive hormone levels 14 , 18 , 26 , 27 . In males, the urinary BP-3 concentration was found to be associated with significantly lower serum total testosterone levels in a cross-sectional study with 588 adolescents 27 . The same association was also observed in a single-blinded study, which measured the plasma testosterone levels of 15 males after topical application of BP-3 containing cream 14 . The author, however, indicated that the difference was more likely due to normal biological variations in hormone levels, because the statistical difference was also evident in blood samples drawn prior to sunscreen application. The clinical significance of BP-3 effect on testosterone level may require further studies as two other studies found no association between BP-3 level and male semen quality or infertility 23 , 25 . In females, on the other hand, there was no statistically significant association between urinary BP-3 concentration and reproductive hormone levels, such as estradiol, progesterone, FSH and LH 14 , 18 , 26 .

Besides analysing the reproductive hormone levels, the endocrine disrupting potential of BP-3 was evaluated by measuring the age of pubertal onset by two prospective cohort studies. Each study found contradicting association, one showing a positive and the other showing a negative association between the BP-3 urine levels and the age of pubertal onset 28 , 29 . Therefore, the effect on pubertal development is inconclusive.

There is growing evidence suggesting that exposure to environmental chemicals, such as phthalates, bisphenol A and multiple endocrine disrupting chemicals (EDCs), could have adverse consequences on renal function and might contribute to cumulative renal injury. One case-control study evaluated whether the exposure to BP-3 can be a risk factor for chronic kidney diseases 30 . When they measured the albumin-to-creatinine ratio (ACR), a kidney function marker, and the urinary concentrations of BP-1, a BP-3 metabolite, of 441 female participants, they found a significant association between BP-1 and ACR, suggesting BP-3 as a potential contributing factor to kidney injury.

Xue et al. compared the urinary concentration of BP-3 in 49 obese Indian children and 27 non-obese controls to examine whether exposure to BP-3 is associated with childhood obesity 31 . The results showed no significant association between BP-3 and childhood obesity.

3.2.2. Effects on Fetal and Neonatal Development

The developing embryo and fetus are particularly vulnerable to endocrine disrupting chemicals (EDCs) such as BP-3, because they can potentially interfere with the hormones, neurotransmitters and growth factors that are critical for normal development 32 , 33 . Since BP-3 is known to cross blood-placenta barrier and enter amniotic fluid and breast milk, the safety concern regarding the use of sunscreen in pregnant women has increased 34 . Thirteen studies assessed the association between prenatal BP-3 exposure and offspring’s development. In all studies, the level of prenatal BP-3 exposure was determined by the mother’s urinary concentration of BP-3 during pregnancy, and the target outcome was evaluated from the offspring through post-birth follow-up. Overall, the prenatal concentration of BP-3 did not have biologically significant effects on the development of offspring ( Table 3 ). Studies found no statistically significant association between prenatal BP-3 exposure and the offspring’s sex ratio, birth weight, pubertal development, body fat mass, intelligence quotient and behaviour 35 - 44 . However, a few studies reported the potential risk of prenatal BP-3 exposure on offspring development 45 - 47 .

The study by Wolff et al. found that prenatal BP-3 exposure was associated with increased birth weight in boys, but four other studies reported no association between prenatal BP-3 and offspring’s birth weight 45 . In a case control study, Huo et al. compared the urinary concentration of BP-3 from 101 mothers with children diagnosed with Hirschsprug’s disease (HSCR) and 322 controls, and reported that maternal BP-3 urinary level was associated with higher odds of having a child with HSCR 46 . However, the urine samples from mothers were collected after child was born, and therefore the observed concentration does not necessarily reflect the prenatal BP-3 level. Buckley et al. studied the association between prenatal BP-3 exposure and the risk of developing allergy or immune disorders in offspring 47 . The results actually shows that the higher prenatal exposure of BP-3 was associated with a lower risk of wheeze in children.

3.3. Octinoxate

3.3.1. effects on organ system.

Octinoxate (octyl methoxycinnamate; OMC), like BP-3, is also considered as EDC 8 , 48 , 49 . However, the effect of OMC exposure on human health is insufficiently investigated compared to that of BP-3. A paucity of studies may be attributed to its relatively low dermal penetration and systemic absorption compared to that of BP-3 11 . When female participants applied the same amount of cream containing either 10% OMC or BP-3 containing cream, the maximum plasma concentration was 7 ng/mL for OMC, whereas 187 ng/mL for BP-3 11 .

Only two studies were found on the effect of OMC on human physiology, which were published by the same author. In both studies, 32 participants applied a cream with 10% of BP-3, OMC and 4-MBC for a week, and its effect on the levels of reproductive hormones and thyroid hormones was reported in 2004 and 2007, respectively 14 , 21 . Neither reproductive hormone nor thyroid hormone levels were remarkably affected, indicating that short-term topical application of OMC did not disrupt the regulation of thyroid hormone.

3.3.2. Effects on Fetal and Neonatal Development

We could not find any human study that evaluated the effect of high systemic levels of OMC on fetal and neonatal development.

4. Discussion

The primary goal of our review was to understand whether elevated systemic levels of BP-3 and OMC can cause negative health consequences in humans. Among many sunscreen ingredients, we focused on BP-3 and OMC as their toxicity to aquatic species and their endocrine-disrupting potential make them high-priority candidates for safety assessment. The endocrine disruptive effect and developmental toxicity of BP-3 and OMC in cell line and animals are well documented, but their impact on humans has not been addressed in great detail. Aside from sunscreens, BP-3 and OMC are frequently used in cosmetics, shampoo, lip balms and fragrances, so the safety assessment of these compounds are of particular importance. As previously mentioned, the number of studies that investigated the health impact from systemic absorption of sunscreen is significantly scarce. On the other hand, we found 29 studies that investigated the impact of high systemic level of BP-3 (n=29) or OMC (n=2, also included in BP-3) on a wide range of health outcomes in endocrine, reproductive, metabolic, renal, dermatologic, and developmental systems. Our systematic review demonstrated that current evidence does not strongly support a causal relationship between the systemic level of BP-3 or OMC and adverse health outcome in humans.

The major limitation of our study, however, is that we could not determine the actual contribution of sunscreen on the systemic levels of BP-3 and OMC, and therefore cannot verify the long-term risk of using sunscreen containing BP-3 or OMC. Most studies included an analysis of urinary concentration as an exposure biomarker, which may result from exposure to environmental means other than sunscreen absorption. None of the studies, except 2, evaluated the health outcome using sunscreen as a main route of exposure. It remains to identify the systemic levels of BP-3 and OMC among chronic sunscreen users and use those values to re-evaluate its association with health effects.

In fact, the previous study by Janjua et al. provides an insight into the contribution of transdermal absorption on the systemic level of BP-3 and OMC by comparing the plasma and urine concentration before and after sunscreen application in a group of 32 volunteers 11 . Prior to sunscreen application, the plasma and urine concentration for BP-3 and OMC were below the level of detection (3.9 ng/mL) in most subjects. However, after the first whole-body application of sunscreens containing 10% of BP-3 and OMC, the median plasma concentrations rose to 238 ng/mL for BP-3 and 16 ng/mL for OMC within the first two hours. The dramatic increase of plasma concentrations after sunscreen application suggests that a large amount of systemic circulation of BP-3 and OMC could be attributed to sunscreen absorption.

The most recent study by Matta et al. indeed replicates the results reported by Janjua et al. When participants applied sunscreen products containing 6% BP-3, the geometric mean maximum plasma concentration was elevated to 209.6 ng/mL from undetectable level of concentration within two hours, resembling the pharmacokinetics observed from the previous study. Their study also highlighted a long terminal half-life of BP-3 and drug accumulation by measuring the plasma concentration at constant intervals over 7 days after first sunscreen application.

A substantial accumulation of BP-3 in the body from repeated sunscreen application was also mentioned in a previous study by Gonzalez et al. When subjects applied sunscreen containing 4% BP-3 for five days, they continued to excrete significant amounts of BP-3 up to five days after the last application 10 .

The evidence of substantial systemic absorption and accumulation of BP-3 prompts a thorough investigation of the long-term risks of BP-3 containing sunscreen use. Although current evidence does not show a significant correlation between the systemic level of BP-3 and adverse health effects, further studies need to be done to determine the systemic effects resulting from long-term sunscreen use and whether steady state levels exceed the threshold for toxic biological effects.

OMC, unlike BP-3, exhibits low dermal penetration and systemic absorption compared to that of BP-3, which may explain a lack of investigation into its potential health impact 11 . Nevertheless, the median toxic dose (TD 50 ), the dose at which toxicity occurs in 50% of cases, is different for each compound, so the low systemic absorption of OMC does not prove its relative safety. More importantly, the topical application of OMC results in systemic absorption greater than 0.5 ng/mL, a threshold established by the FDA for waiving toxicology assessment, and therefore further drug safety assessment on OMC is crucial.

5. Conclusion

In this systematic review, we did not find a strong support for a causal relationship between the systemic level of BP-3 or OMC and adverse health outcomes. The elevated systemic level of BP-3 did not have adverse effect on fertility, childhood adiposity, and fetal and neonatal development, but its impact on thyroid and reproductive hormone levels, pubertal development, kidney function and the immune system will require further investigations. The health consequences of an elevated OMC level has been less extensively studied presumably due to its poor dermal absorption and low serum concentrations relative to other sunscreen compounds. The current evidence shows that topical application of OMC does not have biologically significant effect on thyroid and reproductive hormone levels. To evaluate the long-term risk of exposure to BP-3 or OMC from sunscreens, a well-designed longitudinal randomized controlled trial is of high priority.

6. Questions (answers highlighted)

• Avobenzone and octisalate
• Oxybenzone and octinoxate
• Zinc oxide and titanium dioxide
• Octocrylene and trolamine salicylate
• Studies showed that they can cause damage on coral reef and marine species.
• Studies showed that they can lead to higher risk of melanoma.
• Studies showed that they can monopolize the sale of sunscreens.
• Studies showed that they can cause digestive problems when ingested.
• Breast milk
• All of the above
• Thyroid hormone level
• Testosterone level
• Kidney function
• Heart failure risk

The authors have no conflicts of interest to disclose. The authors did not receive financial support to complete this research

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• Introduction
• Conclusions
• Article Information

Randomization was conducted in block sizes of 4 and included equal numbers of women and men in each treatment group.

Vertical shaded regions indicate the 6-hour window (eg, at 0, 2, 4, and 6 hours) of sunscreen application; solid horizontal lines indicate the 0.5-ng/mL plasma concentration threshold; dashed horizontal lines indicate lower limit of quantitation (LLOQ). LLOQs were 0.2 ng/mL for avobenzone, 0.4 ng/mL for oxybenzone, 0.4 ng/mL for octocrylene, and 0.2 ng/mL for ecamsule. All samples below the LLOQ were set to 0.1 ng/mL for plotting individual profiles. Spray 1, spray 2, and lotion did not contain ecamsule; cream did not contain oxybenzone. Geometric mean pharmacokinetic profiles are shown in eFigure 1 in Supplement 2.

Vertical shaded regions indicate the 6-hour window (eg, arrows denote dosing at 0, 2, 4, and 6 hours) of sunscreen application; solid horizontal lines indicate the 0.5-ng/mL plasma concentration threshold; dashed horizontal lines indicate lower limit of quantitation (LLOQ). LLOQs were 0.2 ng/mL for avobenzone, 0.4 ng/mL for oxybenzone, 0.4 ng/mL for octocrylene, and 0.2 ng/mL for ecamsule. All samples below the LLOQ were set to 0.1 ng/mL for plotting individual profiles. Spray 1, spray 2, and lotion did not contain ecamsule; cream did not contain oxybenzone. Geometric mean pharmacokinetic profiles are shown in eFigure 2 in Supplement 2.

Study Protocol and Statistical Analysis Plan

eMethods 1. Bioanalytical Method Conditions for Avobenzone and Oxybenzone

eMethods 2. Bioanalytical Method Conditions for Octocrylene

eMethods 3. Bioanalytical Method Conditions for Ecamsule

eTable 1. List of Active and Inactive Ingredients of the Sunscreen Products

eTable 2. Demographics

eTable 3. Complete Pharmacokinetic Parameters of Sunscreen Active Ingredients

eTable 4. Incidence and Number of Adverse Events by Treatment Group

eTable 5. Comparison of Day 4 With Day 1 Values of AUC and C max of Sunscreen Active Ingredients

eFigure 1. Geometric Mean Concentration Profiles (All Data)

eFigure 2. Geometric Mean Concentration Profiles (Day 1)

eDictionary. Data Dictionary for Participant Data Listings

eReferences

Deidentified Participant Data

Data Sharing Statement

• Filling in the Evidence About Sunscreen JAMA Editorial June 4, 2019 Robert M. Califf, MD; Kanade Shinkai, MD, PhD
• Risk Uncertain From Sunscreen Ingredients in Blood JAMA Medical News & Perspectives April 21, 2020 This Medical News article is an interview with FDA scientist David Strauss, MD, PhD, about his recent studies in JAMA investigating sunscreen safety. Jennifer Abbasi

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Matta MK , Zusterzeel R , Pilli NR, et al. Effect of Sunscreen Application Under Maximal Use Conditions on Plasma Concentration of Sunscreen Active Ingredients : A Randomized Clinical Trial . JAMA. 2019;321(21):2082–2091. doi:10.1001/jama.2019.5586

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Effect of Sunscreen Application Under Maximal Use Conditions on Plasma Concentration of Sunscreen Active Ingredients : A Randomized Clinical Trial

• 1 Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
• 2 Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
• 3 Spaulding Clinical Research, West Bend, Wisconsin
• 4 Division of Nonprescription Drug Products, Office of Drug Evaluation IV, Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
• 5 Office of Drug Evaluation IV, Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
• Editorial Filling in the Evidence About Sunscreen Robert M. Califf, MD; Kanade Shinkai, MD, PhD JAMA
• Medical News & Perspectives Risk Uncertain From Sunscreen Ingredients in Blood Jennifer Abbasi JAMA

Question   What is the maximum plasma concentration of active ingredients of various types of sunscreen formulations under maximal use conditions?

Findings   In this randomized clinical trial that included 24 healthy participants and application of 4 commercially available sunscreen formulations, maximum plasma concentrations (geometric mean [coefficient of variation]) for the active ingredient avobenzone were 4.0 (60.9%), 3.4 (77.3%), 4.3 (46.1%), and 1.8 (32.1%) ng/mL for 2 different sprays, a lotion, and a cream, respectively.

Meaning   The systemic absorption of sunscreen active ingredients supports the need for further studies to determine the clinical significance of these findings.

Importance   The US Food and Drug Administration (FDA) has provided guidance that sunscreen active ingredients with systemic absorption greater than 0.5 ng/mL or with safety concerns should undergo nonclinical toxicology assessment including systemic carcinogenicity and additional developmental and reproductive studies.

Objective   To determine whether the active ingredients (avobenzone, oxybenzone, octocrylene, and ecamsule) of 4 commercially available sunscreens are absorbed into systemic circulation.

Design, Setting, and Participants   Randomized clinical trial conducted at a phase 1 clinical pharmacology unit in the United States and enrolling 24 healthy volunteers. Enrollment started in July 2018 and ended in August 2018.

Interventions   Participants were randomized to 1 of 4 sunscreens: spray 1 (n = 6 participants), spray 2 (n = 6), a lotion (n = 6), and a cream (n = 6). Two milligrams of sunscreen per 1 cm 2 was applied to 75% of body surface area 4 times per day for 4 days, and 30 blood samples were collected over 7 days from each participant.

Main Outcomes and Measures   The primary outcome was the maximum plasma concentration of avobenzone. Secondary outcomes were the maximum plasma concentrations of oxybenzone, octocrylene, and ecamsule.

Results   Among 24 participants randomized (mean age, 35.5 [SD, 1.5] years; 12 (50%] women; 14 [58%] black or African American; 14 [58%]), 23 (96%) completed the trial. For avobenzone, geometric mean maximum plasma concentrations were 4.0 ng/mL (coefficient of variation, 6.9%) for spray 1; 3.4 ng/mL (coefficient of variation, 77.3%) for spray 2; 4.3 ng/mL (coefficient of variation, 46.1%) for lotion; and 1.8 ng/mL (coefficient of variation, 32.1%). For oxybenzone, the corresponding values were 209.6 ng/mL (66.8%) for spray 1, 194.9 ng/mL (52.4%) for spray 2, and 169.3 ng/mL (44.5%) for lotion; for octocrylene, 2.9 ng/mL (102%) for spray 1, 7.8 ng/mL (113.3%) for spray 2, 5.7 ng/mL (66.3%) for lotion, and 5.7 ng/mL (47.1%) for cream; and for ecamsule, 1.5 ng/mL (166.1%) for cream. Systemic concentrations greater than 0.5 ng/mL were reached for all 4 products after 4 applications on day 1. The most common adverse event was rash, which developed in 1 participant with each sunscreen.

Conclusions and Relevance   In this preliminary study involving healthy volunteers, application of 4 commercially available sunscreens under maximal use conditions resulted in plasma concentrations that exceeded the threshold established by the FDA for potentially waiving some nonclinical toxicology studies for sunscreens. The systemic absorption of sunscreen ingredients supports the need for further studies to determine the clinical significance of these findings. These results do not indicate that individuals should refrain from the use of sunscreen.

Trial Registration   ClinicalTrials.gov Identifier: NCT03582215

Quiz Ref ID Sunscreens prevent skin damage by reflecting, absorbing, and/or scattering UV radiation and are regulated as over-the-counter (OTC) drug products in the United States. 1 - 4 For some individuals, sunscreen products may be applied in substantial amounts multiple times every day over the course of a lifetime as both primary sunscreen products, starting from an age of 6 months, and as ingredients in cosmetic products. 5 Application to the skin can result in multiple grams of sunscreen being applied in a day, even with modest use. 5 Although OTC sunscreen products are widely used, little is known about systemic exposure for most active ingredients. 6 Understanding the extent of systemic exposure of these products is important, as even a low percentage of systemic absorption (eg, 0.1%) could represent a significant systemic exposure (eg, milligrams of ingredient being systemically absorbed per day). 5 The clinical relevance of systemic exposure is not well understood.

Quiz Ref ID The US Food and Drug Administration (FDA) guidance titled “Guidance for Industry: Nonprescription Sunscreen Drug Products Safety and Effectiveness Data” (sunscreen guidance) 1 recommends an assessment of the human systemic absorption of sunscreen ingredients with a maximal usage trial 7 , 8 and a nonclinical safety assessment including dermal carcinogenicity and embryofetal toxicity. The FDA sunscreen guidance 1 and the proposed rule for the OTC sunscreen monograph 6 note that some nonclinical toxicology studies (ie, systemic carcinogenicity and additional developmental and reproductive studies) may be waived if results of an adequately conducted human pharmacokinetic maximal usage trial show a steady state blood level less than 0.5 ng/mL and an adequately conducted toxicology assessment does not reveal any potential safety concerns. 9 , 10 The objective of the current study was to determine the systemic exposure of active ingredients (avobenzone, oxybenzone, octocrylene, and ecamsule) present in 4 commercially available sunscreen products of different formulation types under maximal usage conditions.

The study protocol was approved by the FDA Research in Human Subjects Committee and the clinical site’s local institutional review board (Advarra [ https://www.advarra.com ]). All participants provided written informed consent. The protocol and statistical analysis plan are available in Supplement 1 .

This was an open-label, randomized, 4-group parallel study conducted at a phase 1 clinical pharmacology unit in the United States to evaluate the effects of multiple applications of 4 different topical sunscreen formulations (eTable 1 in Supplement 2 ) in healthy adult participants ( Table 1 ; eTable 2 in Supplement 2 ; deidentified participant data available in Supplement 3 ). Study participants remained in the clinic for up to 7 days and were not exposed to direct sunlight during the study. The study product was weighed in advance and applied by a qualified study team member. Each group had 6 participants (3 men, 3 women) who received a single formulation. Thirty blood samples were collected over 7 days (day 1: 0, 0.5, 1, 1.5, 2, 4, 6, 8, 9, 10, 12, and 14 hours after first sunscreen application; day 2: 23, 28, and 33 hours; day 3: 47, 52, and 57 hours; day 4: 71, 73, 74, 76, 78, 81, 82, 84, and 86 hours; day 5: 95 hours; day 6: 120 hours; and day 7: 144 hours). Two milligrams of sunscreen per 1 cm 2 was applied to 75% of body surface area (area outside of normal swimwear; see Pharmacy Manual in Supplement 1 ) 4 times per day for 4 days (at 0, 2, 4, and 6 hours on day 1; 24, 26, 28, and 30 hours on day 2; 48, 50, 52, and 54 hours on day 3; and 72, 74, 76, and 78 hours on day 4; see Pharmacy Manual in Supplement 1 ). This application regimen was chosen because sunscreens are labeled to be applied at least every 2 hours and may be applied for multiple days in a row, such as might occur when outside in the sun. Plasma concentrations of each active ingredient were assessed with validated liquid chromatography with tandem mass spectrometry methods 11 (eMethods 1-3 in Supplement 2 ).

The study participants were enrolled from July to August 2018. Participants were recruited by standard recruiting for a phase 1 healthy volunteer study (ie, email, text, online). Self-identified race/ethnicity was collected in an open-ended format and recorded by clinical staff as a standard component of a clinical trial. 12 In addition, Fitzpatrick skin type 13 was recorded by clinical staff. Key inclusion criteria were ages 18 through 60 years with a body mass index of 18.5 to 29.9 (calculated as weight in kilograms divided by height in meters squared), negative test results for alcohol and drugs of abuse, and no known or suspected allergies or sensitivities to any components of the sunscreen formulations (additional details available in the study protocol in Supplement 1 ).

The major exclusion criteria were participants with broken, irritated, or unhealed skin or active sunburn and active autoimmune disease, anemia, or other chronic condition that affects blood sample collection. Additionally, participants using any of the listed sunscreen products or products containing the listed active ingredients were excluded from enrollment.

After screening, the 24 participants were randomized to participate in 1 of the 4 treatment groups ( Figure 1 ). The randomization code was generated by a validated database system. Randomization was conducted in block sizes of 4 and included equal numbers of women and men in each treatment group. This study was unblinded to investigators and participants because of the distinct differences between formulations (ie, spray vs lotion or cream), although participants and investigators did not know which spray or which lotion vs cream they received. Allocation concealment was not performed, and bioanalytical laboratory personnel were not blinded to allocation.

The prespecified primary outcome was the maximum plasma concentration of avobenzone over days 1 through 7. Avobenzone is one of the primary UVA filters in the OTC sunscreen monograph, 6 and systemic exposure data for this compound did not exist. The secondary outcomes were the maximum plasma concentrations of oxybenzone, octocrylene, and ecamsule over days 1 through 7.

Along with the primary and secondary outcomes, other exploratory pharmacokinetic parameters were calculated, including time of maximum concentration overall and on days 1 and 4, area under the curve (AUC) of plasma concentration vs time overall and on days 1 and 4, trough concentration or residual concentration each day, and terminal half-life (time required for active ingredient concentration to decrease by 50% during the terminal or final decline phase). All adverse events, whether serious or nonserious and whether related to the study drug, were recorded by study personnel and adjudicated by the principal investigator. No adverse events of special interest were specified.

Two post hoc assessments were performed. The number and percentage of participants with plasma concentrations of active ingredient exceeding 0.5 ng/mL were summarized based on day-1 observations. In addition, accumulation with repeat dosing was assessed by the log-transformed ratio of maximum plasma concentration and AUC on day 4 vs 1.

Because this was an exploratory study to assess general methodology for a sunscreen maximal usage trial and no prior data existed on the systemic absorption of avobenzone, the sample size was determined empirically with reference to the sunscreen guidance recommendation for pilot studies. 7 Data are reported with standard descriptive statistics for all demographics (arithmetic means) and pharmacokinetic parameters (geometric mean, coefficient of variation, confidence intervals, minimum, and maximum). Terminal half-life is reported only for participants with 3 or more concentration values in the terminal portion of the curve and an adjusted coefficient of determination ( R 2 ) greater than 0.70.

In post hoc analyses, accumulation with repeat dosing was assessed by log-transforming AUC and maximum plasma concentration from day 1 and 4 for each product and active ingredient. Data were analyzed using a linear-mixed effects model with fixed effects for day (day 4 vs day 1) and random effects for participant. Point estimates and corresponding 2-sided 90% CIs were obtained from the model and exponentiated to provide estimates of the geometric mean ratio and 90% CI of the ratio; 90% CIs were chosen because they are standard in pharmacokinetic studies. 14 , 15 Exposures on day 4 vs day 1 were considered not significantly different if the lower bound of the 90% CI for all exposure metrics included 1.

Plasma concentrations below the limit of quantitation were assigned as zero during calculation of pharmacokinetic parameters. No adjustments for multiplicity were made in the statistical analyses. Because of the potential for type 1 error due to multiple comparisons, findings for analyses of secondary outcomes, exploratory pharmacokinetic parameters, and post hoc assessments should be interpreted as exploratory. Standard noncompartmental calculations of pharmacokinetic parameters and statistical analyses were performed in R version 3.4.3 (R Foundation).

Twenty-four participants (mean age, 35.5 [SD, 10.5] years; 12 [50%] women); 14 [58%] black or African American; 14 [58%] Fitzpatrick skin type 5 or 6) were randomized to 4 sunscreen products ( Table 1 , Figure 1 ). Spray 1 contained 3% avobenzone, 6% oxybenzone, 2.35% octocrylene, and 0% ecamsule; spray 2 contained 3% avobenzone, 5% oxybenzone, 10% octocrylene, and 0% ecamsule; the lotion contained 3% avobenzone, 4% oxybenzone, 6% octocrylene, and 0% ecamsule; and the cream contained 2% avobenzone, 0% oxybenzone, 10% octocrylene, and 2% ecamsule ( Table 1 ).

All participants completed the study except 1 participant receiving the cream, who discontinued on day 2 because of milia. The most common adverse event was rash, which developed in 1 participant (17%) in each group. Adverse events, which included rash, milia, and pruritis, resolved in all participants (all adverse events are listed in eTable 4 in Supplement 2 ).

Approximately 17% of measures (91/540 samples) were below the lower limit of quantitation for spray 1, 13% (68/540 samples) for spray 2, 13% (68/540 samples) for lotion, and 33% (167/501) for cream. All data from the 1 participant who discontinued from the study were included in the analysis up through the last available time point (47 hours).

All 4 sunscreen products resulted in avobenzone exposures, with plasma concentrations exceeding 0.5 ng/mL on day 1 for all products and through day 7 for all products except the cream ( Figure 2 , Table 2 ; eTable 3 in Supplement 2 ). Geometric mean maximum plasma concentrations were 4.0 ng/mL (coefficient of variation, 60.9%) for spray 1; 3.4 ng/mL (coefficient of variation, 77.3%) for spray 2; 4.3 ng/mL (coefficient of variation, 46.1%) for lotion; and 1.8 ng/mL (coefficient of variation, 32.1%) for cream ( Table 2 ). AUC and maximum plasma concentration increased from day 1 to day 4 for all 4 products ( Table 2 ; eTable 5 in Supplement 2 ), consistent with drug accumulation. All formulations had exposure exceeding 0.5 ng/mL on day 1, with the majority of participants reaching that threshold within 6 hours after the first application ( Table 3 and Figure 3 ). There was a long terminal half-life (mean range, 33-55 hours) ( Table 2 ).

All 3 products with oxybenzone resulted in oxybenzone exposure, with plasma concentrations exceeding 20 ng/mL on day 7. Geometric mean maximum plasma concentrations were 209.6 ng/mL (coefficient of variation, 66.8%) for spray 1; 194.9 ng/mL (coefficient of variation, 52.4%) for spray 2; and 169.3 ng/mL (coefficient of variation, 44.5%) for lotion ( Table 2 ). AUC was numerically higher on day 4 compared with day 1 for all 3 products, consistent with drug accumulation, although only spray 1 and lotion had 90% CIs excluding unity ( Table 2 ; eTable 5 in Supplement 2 ). All participants who received formulations containing oxybenzone had plasma concentrations exceeding 0.5 ng/mL within 2 hours after a single application on day 1 ( Table 3 and Figure 3 ). There was a long terminal half-life (mean range, 24-31 hours) ( Table 2 ).

All 4 products resulted in octocrylene exposures, with plasma concentrations exceeding 0.5 ng/mL, starting from day 1 and lasting through day 7. Geometric mean maximum plasma concentrations were 2.9 ng/mL (coefficient of variation, 102%) for spray 1; 7.8 ng/mL (coefficient of variation, 113.3%) for spray 2; 5.7 ng/mL (coefficient of variation, 66.3%) for lotion; and 5.7 ng/mL (coefficient of variation, 47.1%) for cream ( Table 2 ). AUC increased from day 1 to day 4 for all 4 products, and maximum plasma concentration was numerically higher on day 4 compared with day 1 ( Table 2 ; eTable 5 in Supplement 2 ), consistent with drug accumulation. All participants who received the 3 products with the highest octocrylene product composition (spray 2, lotion, cream) had octocrylene plasma concentrations exceeding 0.5 ng/mL within 6 hours of the first administration ( Table 3 and Figure 3 ). There was a long terminal half-life (mean range, 42-84 hours) ( Table 2 ).

The cream was the only product containing ecamsule. The geometric mean maximum plasma concentration was 1.5 ng/mL (coefficient of variation, 166.1%) ( Table 2 ). Five of 6 participants had an ecamsule plasma concentration exceeding 0.5 ng/mL on day 1 ( Table 3 and Figure 3 ). Some pharmacokinetic measures could not be calculated because 109 of 167 time points were below the assay limit of quantitation (0.2 ng/mL).

Quiz Ref ID This randomized clinical trial demonstrated systemic exposure of 4 commonly used sunscreen active ingredients on application of sunscreen products under maximal use conditions consistent with current sunscreen labeling (ie, apply at least every 2 hours). All 4 sunscreen active ingredients tested resulted in exposures exceeding 0.5 ng/mL. The clinical effect of plasma concentrations exceeding 0.5 ng/mL is unknown, necessitating further research.

Quiz Ref ID Absorption of some sunscreen ingredients has been detected in other studies; however, significant data gaps exist. 16 - 18 In the recent FDA proposed rule for the OTC monograph, 6 2 active ingredients (zinc oxide and titanium dioxide) were found to be generally recognized as safe and effective, while for 12 active ingredients (cinoxate, dioxybenzone, ensulizole, homosalate, meradimate, octinoxate, octisalate, octocrylene, padimate O, sulisobenzone, oxybenzone, and avobenzone) there were insufficient data to make a “generally recognized as safe and effective” determination; thus, more data have been requested from the manufacturers. Avobenzone, oxybenzone, and octocrylene were part of the present study; of note, ecamsule is marketed under a New Drug Application and is not part of the OTC monograph.

Oxybenzone, along with some other sunscreen active ingredients including octocrylene, has been found in human breast milk. 19 In addition, oxybenzone has been detected in amniotic fluid, urine, and blood. 6 Furthermore, some studies in the literature have raised questions about the potential for oxybenzone to affect endocrine activity. 6 , 20 No prior plasma concentration data existed for avobenzone or octocrylene, while ecamsule use was shown to result in limited but detectable exposure in a study conducted under what would be considered submaximal usage conditions today. 21 Currently, multiple active ingredients lack nonclinical safety assessment data, including systemic carcinogenicity and additional developmental and reproductive studies to determine the clinical significance of the level of absorption of sunscreen active ingredients.

This study was performed to demonstrate the feasibility of conducting a sunscreen maximal usage trial 7 and obtain preliminary data on sunscreen active ingredients. It was not intended to be a definitive maximal usage trial study. In this study, a total of 6 participants per formulation was sufficient to detect systemic exposure exceeding 0.5 ng/mL for the tested ingredients but not to delineate the absorption across the entire potential population that uses sunscreens.

The 0.5-ng/mL threshold is based on the principle that the level would approximate the highest plasma level below which the carcinogenic risk of any unknown compound would be less than 1 in 100 000 after a single dose. 1 , 6 This Threshold of Toxicological Concern (TTC) concept was first adopted by FDA in the regulation of food packaging substances that can migrate into food. 9 The threshold value is also consistent with the TTC applied to pharmaceutical drug substance impurities in the International Council for Harmonisation “Guidance for Industry: M7 (R1) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk.” 10 That document recommends a TTC of 1.5 μg/d, when appropriate, which was translated to 0.5 ng/mL for sunscreen active ingredients, assuming a circulating plasma volume of approximately 3 L. Application of this concept was considered acceptable during the determination of the “generally recognized as safe and effective” status of sunscreen active ingredients because such ingredients will be supported by extensive human use and absence of other pharmacologic or toxicologic signals from the nonclinical assessment recommended in the FDA sunscreen guidance. Application of such a threshold concept might not be appropriate or clinically meaningful for chemicals or chemical classes with effects on the human body, beyond that intended as sunscreen.

While the current study was purposefully designed to represent maximal usage per sunscreen labels (ie, apply at least every 2 hours) to areas of the body outside of normal swimwear over multiple days as might occur at the beach, absorption exceeding 0.5 ng/mL occurred on day 1 ( Figure 3 and Table 3 ) and for 3 of the 4 active ingredients lasted until day 7 ( Figure 2 ). A second phase of this study will use a different design to investigate additional questions raised by this study, including the maximum plasma concentration after a single application, the skin concentration during the washout phase, the plasma concentration up to 17 days after the last dose, and the systemic exposure to additional commonly used sunscreen ingredients, including octinoxate, homosalate, and octisalate.

Quiz Ref ID This study has several limitations. First, the study was conducted in indoor conditions without exposure to heat, sunlight, and humidity, which may alter or modify the rate of absorption of sunscreen active ingredients. While this is a limitation, the study was designed to collect informative data in a standardized manner to design subsequent studies. Second, the study was not designed to assess differences in absorption by formulation type, Fitzpatrick skin type, or participant age. However, as shown in the individual participant absorption profiles ( Figure 2 and Figure 3 ), there was consistent absorption of multiple sunscreen active ingredients across the different formulation types, Fitzpatrick skin types, and ages in the study. Third, the study was conducted with multiple applications of sunscreen products as per the labeled dosage regimen and not evaluated on single-dose application, so maximum plasma concentration and additional pharmacokinetic characteristics after a single application were not determined in this study.

In this preliminary study involving healthy volunteers, application of 4 commercially available sunscreens under maximal use conditions resulted in plasma concentrations that exceeded the threshold established by the FDA for potentially waiving some nonclinical toxicology studies for sunscreens. The systemic absorption of sunscreen ingredients supports the need for further studies to determine the clinical significance of these findings. These results do not indicate that individuals should refrain from the use of sunscreen.

Corresponding Author: David G. Strauss, MD, PhD, Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, WO64-2072, Silver Spring, MD 20993 ( [email protected] ).

Accepted for Publication: April 12, 2019.

Published Online: May 6, 2019. doi:10.1001/jama.2019.5586

Author Contributions: Drs Matta and Strauss had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Matta, Zusterzeel, Patel, Oh, Bashaw, Zineh, Sanabria, Adah, Coelho, Wang, Furlong, Ganley, Michele, Strauss.

Acquisition, analysis, or interpretation of data: Matta, Zusterzeel, Pilli, Patel, Volpe, Florian, Kemp, Godfrey, Wang, Michele, Strauss.

Drafting of the manuscript: Matta, Zusterzeel, Sanabria, Strauss.

Critical revision of the manuscript for important intellectual content: Matta, Zusterzeel, Pilli, Patel, Volpe, Florian, Oh, Bashaw, Zineh, Kemp, Godfrey, Adah, Coelho, Wang, Furlong, Ganley, Michele, Strauss.

Statistical analysis: Matta, Zusterzeel, Florian, Wang.

Obtained funding: Wang, Michele, Strauss.

Administrative, technical, or material support: Matta, Zusterzeel, Pilli, Patel, Bashaw, Zineh, Kemp, Adah, Coelho, Wang.

Supervision: Patel, Sanabria, Wang, Furlong, Ganley, Michele, Strauss.

Conflict of Interest Disclosures: None reported.

Funding/Support: The study was funded by the US Food and Drug Administration.

Role of the Funder/Sponsor: The FDA oversaw the design and overall conduct of the study including overseeing the management, analysis, and interpretation of the data. The FDA also prepared, reviewed, and approved the manuscript for submission for publication.

Additional Contributions: We are deeply grateful to the study participants and all the nurses and physicians from Spaulding Clinical Research who contributed to the dosing and pharmacokinetic sample collection. We also thank Robert Gump, BS (FDA), and Suresh Narayanasamy, PhD (FDA), who performed this work as a part of their normal duties.

Data Sharing Statement: See Supplement 4 .

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Sunscreen FAQs

Sun protection resource center.

Looking for information on sunscreen? Visit the Academy's Sun Protection Resource Center.

Seeking shade, wearing sun-protective clothing — including a lightweight and long-sleeved shirt, pants, a wide-brimmed hat, and sunglasses with UV protection — and wearing sunscreen on all skin not covered by clothing — are all important behaviors to reduce your risk of skin cancer. Sunscreen products are regulated as over-the-counter drugs by the U.S. Food and Drug Administration (FDA).

Scientific evidence supports the benefits of sun protection, including using sunscreen to minimize short-term and long-term damage to the skin from the sun’s rays.

Who needs sunscreen?

Everyone. Sunscreen use can help prevent skin cancer by protecting you from the sun’s harmful ultraviolet (UV) rays. Anyone can get skin cancer, regardless of age, gender, or skin tone. In fact, it is estimated that one in five Americans will develop skin cancer in their lifetime. 1 Sunscreen can also help prevent premature skin aging, such as wrinkles and age spots, caused by too much unprotected UV exposure. 2-4

What sunscreen should I use?

The American Academy of Dermatology (AAD) recommends that everyone use sunscreen that offers the following:

Broad-spectrum protection (protects against UVA and UVB rays)

SPF 30 or higher

Water resistance

A sunscreen that offers the above helps to protect your skin from sunburn, early skin aging, 3,4 and skin cancer. However, sunscreen alone cannot fully protect you. In addition to wearing sunscreen on skin not covered by clothing, dermatologists recommend taking the following steps to protect your skin.

Seek shade. The sun’s rays are strongest between 10 a.m. and 2 p.m. If your shadow is shorter than you are, seek shade. 5,6

Wear sun-protective clothing such as a lightweight and long-sleeved shirt, pants, a wide-brimmed hat, and sunglasses with UV protection, when possible. For more effective sun protection, select clothing with an ultraviolet protection factor (UPF) number on the label.

Avoid tanning beds. Ultraviolet light from the sun and tanning beds can cause skin cancer and wrinkling. 3,7,8 If you want to look tan, you may wish to use a self-tanning product, but continue to use sunscreen with it.

Use extra caution near water, snow, and sand as they reflect the damaging rays of the sun, which can increase your chance of sunburn. 9

When should I use sunscreen?

You should apply sunscreen every day on skin not covered by clothing if you will be outside. The sun emits harmful UV rays year-round. Even on cloudy days, up to 80% of the sun’s harmful UV rays can penetrate the clouds. 9

How much sunscreen should I use, and how often should I apply it?

Apply enough sunscreen to cover all skin not covered by clothing. Most adults need about 1 ounce — or enough to fill a shot glass — to fully cover their body.

Don't forget to apply it to the tops of your feet, your neck, your ears, and the top of your head.

Apply sunscreen to dry skin 15 minutes before going outdoors.

Skin cancer also can form on the lips. To protect your lips, apply a lip balm or lipstick that contains sunscreen with an SPF of 30 or higher.

When outdoors, reapply sunscreen approximately every two hours, or after swimming or sweating, according to the directions on the bottle.

Broad-spectrum sunscreens protect against both UVA and UVB rays. What is the difference between the rays?

Sunlight consists of two types of harmful rays that reach the earth — UVA rays and UVB rays. Overexposure to either can lead to skin cancer. In addition to causing skin cancer, here’s what each of these rays does:

UVA rays (or aging rays) can prematurely age your skin, causing wrinkles and age spots, and can pass through window glass.

UVB rays (or burning rays) are the primary cause of sunburn and are blocked by window glass.

The United States Department of Health & Human Services and the World Health Organization’s International Agency of Research on Cancer have declared UV radiation from the sun and artificial sources, such as tanning beds and sun lamps, as a known carcinogen (cancer-causing substance). 8,11

There is no safe way to tan. Every time you tan, you damage your skin. As this damage builds, you speed up the aging of your skin and increase your risk for all types of skin cancer.

Do I need to protect myself from visible light from the sun?

Visible light from the sun can increase skin darkening, also known as hyperpigmentation, particularly for people with darker skin tones. 12 To protect yourself from visible light, seek shade, wear sun-protective clothing, and apply a broad-spectrum sunscreen that says “tinted” on the label and has an SPF of 30 or higher. Tinted sunscreens contain iron oxide, which research shows helps protect people’s skin against the negative effects of visible light from the sun. 12

What type of sunscreen should I use?

The best type of sunscreen is the one you will use again and again. Just make sure it offers broad-spectrum (UVA and UVB) protection, has an SPF of 30 or higher, and is water resistant.

The kind of sunscreen you use is a matter of personal choice and may vary depending on the area of the body to be protected. Available sunscreen options include lotions, creams, gels, ointments, wax sticks, and sprays.

Creams are best for dry skin and applying on the face.

Gels are good for oily complexions and hairy areas, such as the scalp or male chest.

Sticks are good to use around the eyes.

Sprays are sometimes preferred by parents since they are easy to apply to a child’s skin. However, the challenge in using sprays is that it is difficult to know if you have used enough sunscreen to protect all sun-exposed areas of the body. To evenly cover the skin and use spray sunscreen safely, follow these tips:

Spray until your (or your child’s) skin glistens, then rub the sunscreen into the skin to get even coverage.

Do not apply spray sunscreen while you are smoking, near heat, or close to an open flame.

Avoid inhaling spray sunscreen by never spraying it around or near the face or mouth and not spraying it into the wind.

Tinted sunscreens add protection against visible light, in addition to the sun’s UVA and UVB rays. Research has shown visible light can worsen dark spots caused by the sun. Tinted sunscreen that matches with your skin tone can also help you avoid the white residue or “cast” that some sunscreens leave on your skin.

Sunscreen with insect repellant isn’t a product that the AAD recommends. Purchase and apply each product separately, as sunscreens need to be applied generously and often; however, insect repellent should be used sparingly and much less frequently.

Some moisturizers and cosmetics have SPF. While these products are convenient, remember that sunscreen needs to be reapplied approximately every two hours when you’re outdoors.

In addition, keep in mind that while some sunscreens are water resistant, no sunscreen is “waterproof” or “sweatproof.” Sunscreen manufacturers are not allowed to use these terms, as they would be misleading. When using a water-resistant sunscreen, you should reapply it after swimming or sweating.

What is the difference between chemical and physical sunscreens?

The primary difference between these sunscreens is the active ingredients they contain. If the active ingredient in your sunscreen is titanium dioxide, zinc oxide, or both, you have a physical sunscreen. Dermatologists recommend physical sunscreens, also called mineral sunscreens, for people with sensitive skin.

If your sunscreen doesn’t contain titanium dioxide or zinc oxide, you have a chemical sunscreen.

Some sunscreens are called hybrids because they contain one or more active ingredients found in chemical and physical sunscreens. To see what active ingredients your sunscreen has, look at the section on the container labeled “Active Ingredients.”

Whether you have a chemical, physical, or hybrid sunscreen, they all form a protective layer on your skin that absorbs the sun’s rays. 13,14 In addition to absorbing the sun’s rays, physical sunscreens reflect the sun’s rays. 13,14 Any of these sunscreens can effectively protect you from the sun if you select one that is broad spectrum, water resistant, and has an SPF 30 or higher.

Is a high-number SPF better than a low-number one?

Dermatologists recommend using a sunscreen with an SPF of at least 30, which blocks 97% of the sun's UVB rays. Higher-number SPFs block slightly more of the sun's UVB rays, but no sunscreen can block 100% of the sun's UVB rays.

It is also important to remember that high-number SPFs last the same amount of time as low-number SPFs. A high-number SPF does not allow you to spend additional time outdoors without reapplication. As many individuals only apply about 20–50% of the amount of sunscreen needed to achieve the amount of SPF on the label, 10 application of high-SPF sunscreens helps to compensate for this under-application. Sunscreen should be reapplied approximately every two hours when outdoors, even on cloudy days, and after swimming or sweating.

How can I protect my baby or toddler from the sun?

Ideally, parents should avoid exposing babies younger than 6 months to the sun’s rays.

The best way to protect infants from the sun is to keep them in the shade as much as possible, in addition to dressing them in lightweight and long sleeves, pants, a wide-brimmed hat, and sunglasses. If you can’t find shade, create your own using an umbrella, canopy, or the hood of a stroller. Make sure your baby doesn’t get overheated and drinks plenty of fluids. If your baby is fussy, crying excessively, or has signs of sunburn like redness in lighter skin tones or darker areas of skin in darker skin tones on any exposed skin, take them indoors.

If possible, sunscreen use should be avoided in babies younger than 6 months. However, if shade and adequate clothing are not available, parents and caretakers may apply a minimal amount of sunscreen, preferably a physical sunscreen, to their child’s skin. Use sunscreen that offers broad-spectrum protection, water resistance, and SPF 30 or higher. Sunscreen should be washed off your baby’s skin once indoors.

Parents of infants and toddlers 6 months and older may apply a broad-spectrum, water-resistant sunscreen with an SPF of 30 or higher to all skin not covered by clothing, according to the instructions on the product label. When outdoors, sunscreen should be reapplied approximately every two hours, or as often as the label says. Sunscreens that use the ingredients zinc oxide or titanium dioxide, or special sunscreens made for infants or toddlers, may cause less irritation to their sensitive skin. 15

Can I use the sunscreen I bought last summer, or do I need to purchase a new bottle each year? Does it lose its strength?

Dermatologists recommend using sunscreen on all skin not covered by clothing every day when you are outside, not just during the summer. If you are using sunscreen every day and in the correct amount, a bottle should not last long. If you find a bottle of sunscreen that you have not used for some time, here are some guidelines you can follow:

The FDA requires that all sunscreens retain their original strength for at least three years.

Some sunscreens include an expiration date. If the expiration date has passed, throw out the sunscreen.

If you buy a sunscreen that does not have an expiration date, write the date you bought the sunscreen on the bottle. That way, you’ll know when to throw it out.

You also can look for visible signs that the sunscreen may no longer be good. Any obvious changes in the color or consistency of the product mean it’s time to purchase a new bottle.

Avoid leaving sunscreen containers under direct sunlight, or in a hot environment such as inside of the car, as this will speed up the rate that sunscreen ingredients break down.

Will using sunscreen limit the amount of vitamin D I get?

Using sun protection may decrease your skin’s production of vitamin D. However, the AAD recommends that healthy adults should obtain an adequate amount of Vitamin D from a diet that includes foods naturally rich in vitamin D and/or foods/beverages fortified with vitamin D. This approach gives you the vitamin D you need without increasing your risk for skin cancer.

If you are concerned that you are not getting enough vitamin D, you should discuss your options for getting vitamin D with your doctor.

For more information on vitamin D and UV exposure, check out the AAD’s vitamin D fact sheet .

Are sunscreens safe?

The FDA has regulations on sunscreens to keep consumers safe.

One of the FDA’s responsibilities is to review the safety, effectiveness, and quality of sunscreens. To ensure people’s safety, the FDA’s standards for over-the-counter (OTC) sunscreen products are very high. The FDA’s recommendations are based on current scientific evidence, and the science doesn’t show that any sunscreen ingredients currently available in the U.S. are harmful to human health.

The FDA is required to monitor OTC drugs. Part of this responsibility requires the FDA to determine which ingredients are generally regarded as safe and effective (GRASE). If the FDA considers ingredients in a sunscreen as GRASE, then the product can be manufactured without going through an FDA approval process.

The FDA is calling for more data on the following 12 ingredients before determining whether these ingredients can continue to be classified as GRASE:

Ingredients commonly used in the U.S.: Ensulizole, octisalate, homosalate, octocrylene, octinoxate, oxybenzone, avobenzone.

Ingredients not frequently used in the U.S.: Cinoxate, dioxybenzone, meradimate, padimate O, sulisobenzone.

While the FDA is asking for more data, it does not say that the ingredients are unsafe. It does not ask the public to stop using sunscreens that contain any of these ingredients.

A recent study by the FDA looked at four sunscreen ingredients and concluded that absorption of these ingredients into the body supported the need for additional research to determine if the absorption has any effects on a person’s health. As the researchers pointed out, just because an ingredient is absorbed into the bloodstream does not mean that it is harmful or unsafe.

Skin cancer is the most common cancer in the U.S., and unprotected exposure to the sun’s harmful ultraviolet rays is a major risk factor for skin cancer. The AAD remains committed to supporting and enhancing patient care. If you are concerned about the safety of the ingredients in your sunscreen, speak with a board-certified dermatologist to develop a sun-protection plan that works for you.

How do I treat a sunburn?

Your skin can burn if it gets too much sun without proper protection from sunscreen and clothes. To help heal and soothe stinging skin, it is important to begin treating sunburn as soon as you notice it. The first thing you should do is get out of the sun — and preferably indoors.

Once indoors, these dermatologists’ tips can help relieve the discomfort:

Take frequent cool baths or showers to help relieve the pain. Afterward, gently pat your skin dry.

Soothe your sunburn by applying moisturizer containing aloe vera or soy while your skin is still damp and whenever you feel discomfort. You can also apply calamine lotion, place a cool, damp washcloth on the affected area, or take a colloidal oatmeal bath.

Consider taking aspirin or ibuprofen to help reduce any swelling and discomfort from your sunburn.

Drink extra water. A sunburn draws fluid to the skin’s surface and away from the rest of the body. Drinking extra water when you are sunburned helps prevent dehydration.

Do not pop sunburn blisters. Blistering skin means you have a second-degree sunburn. Allowing blisters to heal — instead of popping them — protects you from infection. Keep blisters clean and apply petroleum jelly to protect them while they heal.

Protect your skin from the sun to prevent sunburn and reduce your risk of skin cancer and premature skin aging. Seek shade, wear sun-protective clothing — such as long sleeves, pants, a wide-brimmed hat, and sunglasses with UV protection. Apply a broad-spectrum, water-resistant sunscreen with an SPF of 30 or higher to all skin not covered by clothing.

If your sunburn gets worse, partner with the sun-protection expert, a board-certified dermatologist.

Does the AAD have a position on the environmental impact of sunscreens?

The AAD supports the National Academies of Sciences, Engineering, and Medicine’s recommendation that the U.S. Environmental Protection Agency (EPA) conduct an ecological risk assessment of active sunscreen ingredients to characterize possible risks to aquatic ecosystems and the species that live in them. As the report released in August 2022 makes clear, the science in this area is limited and inconclusive. In addition, the AAD supports the recommendation that studies be conducted to determine how any changes to the availability of active ingredients in sunscreen would impact human health.

It is well established that unprotected exposure to ultraviolet rays is a major risk factor for skin cancer. Since exposure to the sun’s harmful UV rays is the most preventable risk factor for skin cancer, it’s important that everyone protects their skin from the sun.

The use of sunscreen is one way to minimize short-term and long-term damage to the skin from the sun and to reduce the risk of skin cancer. In addition to applying a broad-spectrum, water-resistant sunscreen with an SPF of 30 or higher, the AAD also recommends that people seek shade and wear sun-protective clothing, including a lightweight and long-sleeved shirt, pants, a wide-brimmed hat, and sunglasses.

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2 Food and Drug Administration. Sunscreen: How to Help Protect Your Skin from the Sun. Accessed February 10, 2021.

3 Hughes MC, Williams GC, Baker P, Green AC; Sunscreen and Prevention of Skin Aging, a Randomized Trial. Annals of Internal Medicine. 2013;158(11):781-790.

4 Guan LL, Lim HW, Mohammad TF. Sunscreens and Photoaging: A Review of Current Literature. Am J Clin Dermatol. 2021;22(6):819-828. doi:10.1007/s40257-021-00632-5

5 Holloway L. Atmospheric sun protection factor on clear days: its observed dependence on solar zenith angle and its relevance to the shadow rule for sun protection. Photochem Photobiol 1992;56:229-34.

6 Diffey BL. Time and Place as Modifiers of Personal UV Exposure. Int J Environ Res Public Health. 2018;15(6):1112. Published 2018 May 30. doi:10.3390/ijerph15061112

7 An S, Kim K, Moon S, et al. Indoor Tanning and the Risk of Overall and Early-Onset Melanoma and Non-Melanoma Skin Cancer: Systematic Review and Meta-Analysis. Cancers (Basel). 2021;13(23):5940. Published 2021 Nov 25. doi:10.3390/cancers13235940

8 IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 100D. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon (FR): International Agency for Research on Cancer ; 2012.

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10 Petersen B, Wulf HC. Application of sunscreen− theory and reality. Photodermatology, photoimmunology & photomedicine. 2014 Apr;30(2-3):96-101.

11 NTP (National Toxicology Program). 2021. Report on Carcinogens, Fifteenth Edition.; Research Triangle Park, NC: U.S. Department of Health and Human Services, Public Health Service. https://ntp.niehs.nih.gov/go/roc15 . DOI: https://doi.org/10.22427/NTP-OTHER-1003

12 Lyons AB, Trullas C, Kohli I, Hamzavi IH, Lim HW. Photoprotection beyond ultraviolet radiation: A review of tinted sunscreens. J Am Acad Dermatol. 2021;84(5):1393-1397. doi:10.1016/j.jaad.2020.04.079

13 Cole C, Shyr T, et al. “Metal oxide sunscreens protect skin by absorption, not by reflection or scattering.” Photodermatol Photoimmunol Photomed. 2016 Jan;32(1):5-10.

14 Zundell MP, Wong M, et al. “Letter to the editor: Improving patient communication on sunscreen choice: Updating mechanistic misconceptions.” J Eur Acad Dermatol Venereol Cli. Pract. 2023;1–2.

15 Food and Drug Administration. Consumer Updates: Should You Put Sunscreen on Infants? Not Usually. Accessed May 10, 2022. https://www.fda.gov/consumers/consumer-updates/should-you-put-sunscreen-infants-not-usually

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New developments in sunscreens

• Open access
• Published: 05 August 2023
• Volume 22 , pages 2473–2482, ( 2023 )

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• José Aguilera 1 ,
• Tamara Gracia-Cazaña   ORCID: orcid.org/0000-0002-0523-2076 2 , 3 &
• Yolanda Gilaberte 2 , 3  

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Topical sunscreen application is one of the most important photoprotection tool to prevent sun damaging effects in human skin at the short and long term. Although its efficacy and cosmeticity have significantly improved in recent years, a better understanding of the biological and clinical effects of longer wavelength radiation, such as long ultraviolet A (UVA I) and blue light, has driven scientists and companies to search for effective and safe filters and substances to protect against these newly identified forms of radiation. New technologies have sought to imbue sunscreen with novel properties, such as the reduction of calorific radiation. Cutaneous penetration by sunscreens can also be reduced using hydrogels or nanocrystals that envelop the filters, or by binding filters to nanocarriers such as alginate microparticles, cyclodextrins, and methacrylate polymers. Finally, researchers have looked to nature as a source of healthier products, such as plant products (e.g., mycosporines, scytonemin, and various flavonoids) and even fungal and bacterial melanin, which could potentially be used as substitutes or enhancers of current filters.

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1 Introduction

Primary prevention strategies for avoiding sun damaging effects include different photoprotection measures as a good knowledge of solar UV incidence at earth surface for acquiring behavior of sun avoidance during the peak UV radiation hours (a practical clue is when shadows are shorter than those casting them) and the use of photoprotective clothing, wide-brimmed hats, and sunglasses, and finally, for non-covered skin, the use of broad-spectrum sunscreens is highly extended in general population [ 1 , 2 , 3 ]. Recent years have seen improvements in both the efficacy and cosmeticity of sunscreens. The main objective of sunscreens is to protect against sunburn, which they achieve thanks to the presence of filters that primarily block ultraviolet B (UVB) radiation. Research published in the 1990s highlighted the potential harmful effects of UVA radiation, prompting the addition of UVA filters to sunscreen and the establishment of regulations requiring measurement of the UVA protection factor [ 4 ]. Studies conducted in the 2000s documented the harmful effects of near-infrared radiation on the skin and certain substances, mainly antioxidants, that were added to sunscreen to protect against this type of radiation, although to date there is no validated method to measure the efficacy of this form of protection [ 5 ]. Finally, the harmful effects of visible light (VL), especially blue light and long UVA (380–400 nm), have been demonstrated in recent years, and include hyperpigmentation and photoaging [ 6 , 7 , 8 , 9 ].

In addition to new filters and antioxidants to prevent cutaneous damage caused by sunlight, repair products, especially DNA repair products, have also been included in sunscreen formulas [ 10 ]. Together, these discoveries have led to notable changes in sunscreen formulas, improving their capacity to protect against cutaneous photodamage.

Finally, some filters appear to have deleterious environmental effects, especially in marine environments, and some have been found in the plasma and urine of human users, although no serious effects on human health have been demonstrated to date [ 11 ].

This article reviews the most recent developments in new filters and innovative substances that neutralize sun damage and also repair DNA. We discuss molecules that are currently being investigated and may be marketed in the near future. Furthermore, we describe advances in the development of vehicles that make sunscreens more comfortable to use and increase their adherence.

2 Past, present, and future tasks in the development of sunscreen filters

It is almost 100 years since the first topical formulations for photoprotection were introduced into the market for primary prevention purposes. However, the earliest records of the use of substances, mainly extracted from plants such as rice, jasmine, and lupine, date back to almost 4000 BC in Ancient Egypt, [ 12 ] and the use of minerals such as zinc oxide is described in Indian writings from around 500 BC. [ 13 ] However, it was not until the inter-war period in the twentieth century, when sun and exposure for both tanning and as a healthy habit became widespread, that products to prevent skin damage in the short term, became available. Almost in parallel, pioneers in the fields of chemistry and pharmacy searched for molecules with the ability to absorb wavelengths that caused sunburn, which had already been linked to skin exposure to UVB radiation by Haussner and Vahle in 1922 [ 14 ]. These same authors developed the first commercial formulations based on the UVB-absorbing filters benzyl salicylate and benzyl cinnamate. Other filters developed at the time that enjoyed great commercial success include PABA, which was developed by Eugene Schueller’s team and has survived to the present day, and red petrolatum, which was developed by Benjamin Green during the second World War and marketed as Coppertone: both were formulas designed to curb skin erythema and promote healthy skin tanning [ 12 ]. It was not until 1969 that the first negative effects of UVA (premature skin aging) were described, and formulas containing organic UVA-absorbing molecules such as butyl methoxydibenzoyl methane, patented in 1973 by Roche and approved in Europe in 1978 and by FDA finally in 1996, respectively, were subsequently developed [ 15 , 16 ]. Since then, commercial photoprotection formulations have included combinations of different filter families.

The ideal sunscreen should contain a combination of filters against UVB (e.g., PABA derivatives or cinnamates), filters with UVA2 absorption (e.g., avobenzone) as well as filters that protect against UVA1 wavelengths, which have only recently started to be added to sunscreens in Europe [ 17 , 18 , 19 ]. Octocrylene is commonly used for its double properties, as an UVB-absorbing filter and second by its stabilization properties for the other filters contained in the formula as octinoxate and avobenzone, which are widely used but has poor photostability [ 20 , 21 ]. Other groups of filters are approved in EU for two main reasons: filter size, which minimizes the risk of cutaneous penetration; and a low level of associated photosensitivity. These include molecules with maximum UVB absorption such as ethylexyl triazone, isoamyl methoxycinnamate, and 4 methyl benzylidene camphor, UVA absorption such as Mexoryl SX, and broad-band filters such as dometrizole trisiloxane (Mexoryl XL), bemotrizinol (Tinosorb S), and bisoctrizole (Tinosorb M) [ 22 ].

The combination of UVB and UVA filters has become commonplace over the last 30 years. The objective of these so-called “broad spectrum” sunscreens is actually to protect the skin against almost the entire spectrum of solar UV radiation to different skin biological effects as erythema or persistent pigment darkening. Solar protection factor, or the protection level of a sunscreen based on human UV erythemal action spectrum [ 23 ] was defined in 1974 by Franz Greiter, the creator of the Piz Buin company. UVA PF was later developed to assess psoralen-induced phototoxicity, and finally it was finally stablished by Chardon in 1997 for using persistent pigment darkening as an assessment method. [ 24 , 25 ] The criterion for broad-spectrum formulations was established finally by the European Commission in 2006 in which the UVA protection factor (the potential to prevent persistent pigment darkening) must be at least 1/3 of the SPF (solar protection factor) [ 26 ]. In the US, the 2019 proposed rule is changing requirements for designation of broad-spectrum coverage, “A UVA I/UV ratio of 0.7 or higher, indicating that the product provides a minimum measure of UVA I radiation absorbance relative to total UV radiation (i.e., UVB + UVA) absorbance, in addition satisfying to the 370 nm critical wavelength requirement”. Requiring a UVA I/UV ratio of 0.7 or higher for broad-spectrum products would mean that these products would have a more uniform amount of radiation protection across the UVA I, UVA II, and UVB ranges. [ 27 ]

3 New organic filters for new wavelengths photoprotection

It has taken more than 10 years to introduce new organic molecules to the list of approved sunscreens in the EU. These new filters have been designed to complement the previous combination of UVB and UVA filters by providing enhanced UVA photoprotection, specifically by protecting against wavelengths around and above 400 nm. Their development is the result of recent research into the effects of high energy visible radiation (HEVR), which causes skin hyperpigmentation as well as oxidative stress, immunomodulation, altered hydration levels, and even damage to cellular DNA. [ 6 , 28 , 29 , 30 , 31 , 32 ] HEVR corresponds to wavelengths above 380 nm, including blue light wavelengths up to 450 nm. In 2021, a UVA1-type filter called methoxypropylamino cyclohexenylidene ethoxyethylcyanoacetate (MCE) appeared on the list of EU-approved sunscreens. This filter is designed to cover the lack of efficacy of classical sunscreens above 370 nm. The molecule has an absorption maximum at 385 nm with a molar extinction coefficient of 63.052 (L mol-1 cm-1), and a critical wavelength in the 290–400 nm range of 389 nm. It has good solubility in 50% water/ethanol and is highly thermostable in different media and photostable even in the presence of high O 2 concentrations [ 19 ]. Its efficacy has been demonstrated in combination with other filters both in vitro and in vivo: [ 19 , 33 ] it can protect against damage caused by UVA1 radiation with a maximum of 380 nm in fibroblasts, inhibiting the production of metalloproteinases and the production of IL-6 and IL-8; and it reduces hyperpigmentation, immunosuppression, and photoaging in humans [ 19 ].

The sun filter most recently added (2021) to the EU-approved list is phenylene bis-diphenyltriazine (TriAsorB), a low-molecular-weight molecule (540.6 gmol-1) which, owing to its insolubility in hydrophilic and lipophilic media, gives rise to aggregates in dispersion above 100 nm, meaning that its penetration of the skin is very low. It has a high molar extinction coefficient of 329 nm (52.492 L mol-1 cm-1), and although capable of absorbing from UV to infrared radiation (IR) has maximum absorption around 370 nm, a critical wavelength around 390 nm, and its absorption spectrum reaches a limit of significant efficiency up to 450 nm [ 34 ]. Its efficacy against high energy visible radiation (HEVR) has been demonstrated by its inhibition of the formation of 8-deoxyguanosine in reconstructed skin after exposure to 80 J.cm-2 of blue light (max, 412 nm) [ 35 ]. It also shows efficacy against oxidative DNA damage and the generation of dark cyclobutane pyrimidine dimers (CPDs) when combined in a commercial formulation with other classical UVB and UVB/UVA sunscreens [ 35 ].

New organic sunscreen candidates for inclusion on approved sunscreen lists are still in development, and seek to provide new safe, stable, and even environmentally friendly molecules. Francois-Newton et al. [ 36 ] described a new sunscreen with a potential protective effect against blue light (TFD Blu Voile sunscreen) containing zinc oxide, titanium dioxide, and a trimethylol hexyllactone crosspolymer that acts as a blue light blocking ingredient itself. In vivo, this formulation reduces immediate and persistent hyperpigmentation induced by 415 nm blue light.

Methylene bis-benzotriazolyl tetramethylbutylphenol (Parsol ® Max, DSM) [ 37 ] is a broad-spectrum photostable filter that has also been shown to provide protection in the blue light range.

Bis-(diethylaminohydroxybenzoyl)piperazine (BDBP) is another modern organic candidate blue light filter with an absorption band of 350–425 nm, and combined with classical filters has been shown to improve in vivo photoprotection of human volunteers against pigmentation [ 38 ].

4 Inorganic filters

Inorganic filters appear much less frequently than organic filters on the approved sunscreen lists of various international institutions, and until now have been based mainly on two elements used cosmetically since ancient times: titanium dioxide and zinc oxide [ 39 ]. Due to their low cosmeticity, their use had been relegated to a secondary role, i.e., to accompany other combinations of organic filters or for use alone for infant photoprotection or in patients with photosensitivity to organic filters. However, these mineral filters have recently got an important new status for their incorporation alone or combined with other organic filters. FDA (in its 2019 document) [ 27 ] recognized 22 UVF compounds in use in sunscreen products and classified them as Generally Recognized As Safe and Effective (GRASE) (Category I), those that are Non-GRASE (Category II), and those that require further evaluation (Category III). Titanium dioxide and zinc oxide were designated as GRASE-Category I (Federal Register 84FR6204-6275, 2019-03019). Regarding the ecological aspects of sunscreens, in spite of not really safe UV filter for the nature at all, both TiO2 and ZnO in the non-nano forms (over 100 nm) are mainly recommended and they are extensively included as part of “ocean safe” and “reef safe” sunscreens. [ 40 , 41 , 42 ]. Since the 1990s, they have been used in nano form and recent EU regulations [ 43 ] establish a minimum particle size (nano forms) and prohibit their use in aerosols. Their use is widespread and they will undoubtedly constitute fundamental components of future sunscreen formulations. Their broad absorption spectrum is another feature that makes mineral filters candidates for extensive use: their combination with classical organic filters can achieve an absorption spectrum that includes both visible and UV light. While the nano and micro forms of titanium dioxide offer reduced photoprotection in the UVA1 and visible light spectra, nano forms of zinc oxide are not affected in this way [ 44 ].

As mentioned above, photoprotection against light in the visible spectrum is a current goal of new sunscreens, as a large sector of the population is particularly affected by photoaging and unaesthetic hyperpigmentation, and these issues are exacerbated by HEVR, which has led to an increase in the use of tinted sunscreens [ 45 ]. These formulations consist of a blend of iron oxides (Fe 2 O 3 ) and TiO 2 , molecules that function as VL and UV filters, and different skin colors are mimicked using a combination of different oxidation states of iron oxide, which range from yellow to red or even very dark brown. Currently, tinted SPF 50 + photoprotective formulations can achieve sun protection factors for visible light above 10, based on their wavelength absorption potential against hyperpigmentation in the visible range [ 46 ]. There are very few reports of skin photosensitivity caused by iron oxide, [ 47 ] and tinted formulations have become popular not only as outdoor sunscreens but also as indoor sunscreens to protect against blue light from different electronic devices and artificial light. However, the real effect of these artificial light sources on the skin is minimal compared to sun exposure, [ 48 ] and photoprotection is only justified in cases of indoor exposure combined with sun exposure.

5 New technologies applied to sunscreens to improve efficacy and safety

Organic and inorganic filters are used not only to protect against UV and visible light, but also the effects of IR radiation. The photoaging effect of near-infrared radiation (NIR) on skin has been known for years. [ 49 , 50 ]Tinted sunscreens are very effective against UV and visible radiation: their absorption spectrum reaches wavelengths up to 1300 nm, decreasing by 40–50% the average transmittance of radiation in the 760–1300 nm range (in measurements carried out by our research group following ISO protocols for measuring the UVA protection factor in vitro) [ 51 ]. However, growing alarm around the effects of climate change and increases in mean summer temperatures has increased interest in photoprotection against wavelengths with higher calorific value (e.g., IRB). Thus, new filters called cooling filters have been developed [ 52 ]. These consist of hydrogels with a three-dimensional network structure and high water content, containing hyaluronic acid and tannic acid with a broad-UV spectrum protection (280–360 nm). Adding polyols such as xylitol (2.0 wt%) decreases skin temperature by 6.6 ℃ after 5 min, an effect maintained for a long duration. In addition, these hydrogels have a high moisture content and show excellent adhesion to the skin, antioxidant activity, and a cooling effect.

One of the most important challenges in developing sunscreens is human safety, avoiding penetration through the skin. Thus, the development of appropriate vehicles has major implications for stability, as well as reducing skin permeability and ensuring homogeneous UV filter distribution to ensure optimal performance. The use of polysaccharide structures to form hydrogels increases filter safety by preventing crossing of the skin barrier. Another approach is the use of nanotechnology to generate hydrogels derived from benzofuroazepine to envelop molecules [ 53 ]. The use of cellulose nanocrystals has been shown to increase the efficacy of filters by minimizing their penetration [ 54 ]. Alginate microparticles are effective in increasing the photostability of 2-ethylhexyl 4-methoxycinnamate [ 55 ]. Cyclodextrins are polysaccharides used as inclusion complexes to increase sunscreen efficiency and safety [ 56 ]. These encapsulation techniques are providing novel, safe, and more eco-friendly sunscreens, and can be added to the encapsulation techniques used in many formulations that already are on the market, such as methacrylate polymers (PMMA) [ 57 , 58 ]. Another technique used to prevent filter penetration is the creation of new crystalline structures through the melting and emulsification of filter agglomerates [ 59 ]. Technologies based on semi-crystalline polymers, such as the combination of alkyl acrylate/hydroxyethylacrylate copolymer (netlock technology), can stabilize filters in the formulation, ensuring prolonged permanence on the skin [ 60 ].

6 Natural sources of sunscreens against solar UV and visible light

“Green” approaches to the development topical photoprotectants have produced promising findings in recent years, with researchers and cosmetic developers recognizing the potential of photoprotective products based on natural products. No natural organic sunscreens are currently included in the lists of approved sunscreen filters of the different international regulatory agencies. Most of these substances are considered additives, and act as boosters in the formula, although several such compounds are potential sunscreen candidates owing to their high photoprotective efficacy [ 61 ]. Mycosporine-like amino acids (MAAs) are currently considered promising sunscreen candidates, given the large body of data generated over the last 20 years demonstrating a high degree of photoprotective efficacy [ 62 ]. MAAs are a family of low-molecular-weight molecules isolated from fungi and a variety of marine organisms, and are soluble in aqueous media, showing varying degrees of hydrophobicity. There are different types of MAAs with absorption maxima ranging from 310 nm (MAA-glycine) to 362 nm (usurijene). They have a high molar extinction coefficient, very similar to that of octinoxate and avobenzone, are thermally stable under different conditions, and are photostable at very high UV radiation doses. MAAs cause neither phototoxic nor photoallergy reactions. In addition, some have high antioxidant activity [ 63 , 64 ], and therefore have been incorporated into various photoprotective formulas on the market as extracts or in combination with classic filters [ 65 ]. The main limitation to the use of natural MAAs is the amount of purified substance necessary: several grams are required in each formulation. To overcome this limitation, analogs have been synthesized in the laboratory. Following a simple process, Losantos et al. [ 65 ] developed a group of MAAs similar to natural MAAs, with different maximum wavelengths, very high molar extinction coefficients, and very high photostability. Genetic engineering approaches have also been applied to shinorin, which has been incorporated into the genome of the cyanobacterium Fischerela sp. for mass production [ 66 ].

Scytonemin, a very abundant pigment in Cyanobacteria, is a dimeric compound composed of indolic and phenolic subunits linked with an olefinic carbon atom, and has a maximum absorption spectrum of 386 nm. It is currently being studied for potential use as a UV filter to protect against very long UVA wavelengths and HEVR [ 67 ]. Scytonemin-3a-imine, derived from Scytonema hoffmani after exposure to high doses of solar radiation, shows absorption maxima at 366 and 437 nm [ 68 ]. Currently, its biotechnological production for commercial use is booming. [ 69 ].

Flavonoids are a second group of polyphenol molecules that are promising natural sunscreen candidates. Their molecular structure features aromatic rings and double bonds, conferring absorption across the entire UV spectrum. Among the ideal candidates, quercetin and especially rutin offer both high antioxidant activity and, crucially, high UV absorption potential, reaching SPFs above 35, [ 70 ] although total polyphenols extracted from some leaves and plants can achieve SPF values above 20 [ 71 ]. The traditional herbal formulation, Ubtan, based on different plant seeds (mainly flavonoids), can reach SPF values above 30 [ 72 ].

Lignin, the most abundant flavonoid in nature, is another candidate green sunscreen owing to its high UV absorption capacity (maximum absorption, 283 nm) and its antioxidant activity and biocompatibility. [ 73 ]. The low solubility and dark color of lignin are the main factors limiting its cosmetic use [ 74 ] . However, this limitation has been resolved by self-assembly of the native polymer into highly ordered lignin nanoparticles (LNPs) [ 75 ] and the development of a method to prevent darkening of lignin during the process of delignification for use in sunscreen [ 76 ].

Silymarin, a polyphenol obtained from the milk thistle plant Silybum marianum, is composed of different flavonoids such as silybin, silydianin, and silychristin. This molecule is well known for its antioxidant activity, and has been shown to absorb UVR, with a SPF up to 9 when formulated at 10%, [ 77 ] increasing further when combined with titanium dioxide and zinc oxides [ 78 ]. Again, its transformation into nanoparticles, which increase its solubility, makes it a strong candidate as a UV blocker [ 79 ].

One of the natural substances with potential as a booster, for both oral and topical applications, is the extract of the fern Polypodium leucotomos , which is rich in non-flavonoid catecholic compounds (benzoates and cinnamates such as caffeic acid and its derivative ferulic acid). This phenolic extract has been extensively studied for multiple properties that protect the skin against damage caused by UV and visible solar radiation, mainly due to its high antioxidant activity [ 80 , 81 ]. It also protects against immunosuppression and hyperpigmentation caused by HEVR [ 82 ].

Finally, other natural products include fungal or bacterial melanins, which are potential biocompatible broad-spectrum sunscreens with high antioxidant activity. The addition of melanin derived from Amorphotheca resinae (5%) to sunscreen was shown to increase the SPF from 1 to 2.5, resulting in a critical wavelength of 388 nm and a UVA:UVB ratio of more than 0.81. Moreover, this compound showed antioxidant activity similar to that of ascorbic acid but greater than that of reduced glutathione [ 83 ]. Bacterial melanins such as DHICA from Pseudomonas sp. contains 5,6-dihydroxy indole 2-carboxyc acid (DHICA), which possesses typical eumelanin properties, exerting a photoprotective effect against UVB radiation in mouse fibroblast cells [ 84 ]. In their in vitro study, Kurian et al. demonstrated an increase in the SPF of a commercially available sunscreen following addition of bacterial melanin [ 85 ].

7 Conclusion

The sunscreen field is constantly evolving, with the development of novel compounds and formulations to increase both safety and efficacy. The last year alone has seen many innovations, with many promising molecules still under investigation (summarized in Table 1 ). New filters that provide balanced photoprotection against all forms of harmful solar radiations are already included in available sunscreens, improving their protection against hyperpigmentation, immunosuppression, and photoaging, while new vehicles provide greater protection against filter penetration of the skin. Finally, natural products, mainly derived from marine and terrestrial plants, hold great promise for future methods of skin damage prevention, and have produced a range of promising photoprotective molecules that can be used either alone or combined with sunscreens of mineral origin.

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Aguilera, J., Gracia-Cazaña, T. & Gilaberte, Y. New developments in sunscreens. Photochem Photobiol Sci 22 , 2473–2482 (2023). https://doi.org/10.1007/s43630-023-00453-x

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Sunscreen products: Rationale for use, formulation development and regulatory considerations

Kiriiri geoffrey.

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Received 2019 Feb 28; Accepted 2019 Aug 13; Issue date 2019 Nov.

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Graphical abstract

Keywords: Sunscreens, Photoprotection, Ultraviolet rays, UVA, UVB, Sun protection factor (SPF), Water resistance, Minimum erythemal dose (MED)

The association of sunrays with skin damage have been known since medieval times. The description of the electromagnetic spectrum facilitated the identification of the ultraviolet light spectrum as being responsible for skin damage resulting from prolonged skin exposure. Sunscreens have been used since ancient civilizations with various measures to limit exposure to sun exposure being employed. Awareness of the risks associated with sunrays has been increasing in the last century, and as a result, the science, technologies, and formulation have advanced significantly. The use of sunscreen products continues rising as government health agencies seek to contain increasing cases of UV induced melanomas. Recreational sunbathing and artificial tanning have increased the risk for these diseases significantly. This review article sought to expound the scientific basis of sunscreen use, the classification, formulation, quality control and regulation across the different countries around the world. The literature review was conducted on Google scholar, PubMed, SCOPUS, Cochrane, BMJ, SCIELO among others.

1. Introduction

Repeated exposure of the skin to the sun has the potential to cause both short-term and long-term changes in the structure of the skin. In the short term, repeated exposure results in erythema (reddening) of the skin commonly referred to as sunburns ( Moore, 2013 ). The erythema is followed by activation of melanocytes which increase their rate of melanin production (increased melanization) which darkens the skin appearance otherwise referred to as tanning. Long term effects of repeated exposure include irreversible loss of skin elasticity and may lead to the development of skin cancers, both melanomas and non-melanomas ( Harrison and Bergfeld, 2009 ). The extent of skin damage depends on the duration of exposure, seasonal variations in incident sunrays intensity, geographical location, and host-dependent factors including age, skin color, behavioral factors, immune status among others ( Jou and Tomecki, 2014 , Rigel, 2008 , Harrison and Bergfeld, 2009 ).

The utilization of sunscreens (also referred to as sunprotectants) for protection against the harmful effects of the sun rays has been increasing over the last few decades. This may have resulted from increased awareness about the potentially harmful effects that arise from repeated exposure to the sun. Increased awareness campaigns by the government(s) have also played a role in the increased uptake ( Albert and Ostheimer, 2003 ). Repeated sun exposure increases the risk of three types of cancer: melanoma, basal cell carcinoma, and squamous cell carcinoma with melanomas causing higher mortality while the non- melanoma skin cancers are associated with higher morbidity and aesthetic skin damage ( Schüz and Eid, 2015 , Armstrong and Cust, 2017 , Craythorne and Al-Niami, 2017 ). Different clinical studies have shown that regular use of sunscreens can promote skin cancer reduction, especially melanoma and squamous cell carcinoma ( Green et al., 2011 ). Evidence towards the protective role of sunscreens against photoaging has also been established ( Hughes et al., 2013 ).

The formulation and science of sunscreens have also evolved along with improvements in the scientific knowledge and technologies to improve the formulation characteristics in both efficacy, safety and aesthetic appeal. Increased incidence of skin melanomas has attracted regulatory concerns on the quality of sunscreens resulting in higher demands from the authorities regarding the quality of sunscreen products ( Jansen et al., 2013 ). There are also immense economic gains to be realized given the expensive costs of treatment and loss of economic productivity occasioned by individuals suffering from skin cancers ( U.D. of H. and H. Services, 2014 ). The financial burden of non-melanoma in Australia was projected to surpass 700 million dollars highlighting the huge financial burden skin cancers have on the healthcare systems ( Gordon and Rowell, 2015 ).

This article reviews the science behind the use of sunscreens, the historical perspective of sunscreen use, nature and classification of sunscreens, dosage forms and incidental formulation challenges. The science of ultraviolet light and its inherent potential to cause skin damage is discussed. Determination of product effectiveness, regulatory aspects of sunscreen manufacturing and marketing are also discussed.

The use of sunscreens as photoprotectants has evolved significantly over the last few decades. With increasing awareness of the protection afforded by sunscreens against sunburns, skin aging and melanomas, the demand for sunscreen formulations will invariably increase, and there exists a significant opportunity for pharmaceutical industries to fulfill this demand by manufacturing quality, efficacious, safe and aesthetically appealing sunscreen formulations ( Svarc, 2015 , Tuchinda et al., 2006 ).

1.1. The basis of sunscreen use

Cosmetics are defined as “articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance” ( FDA, 2018a ). Among the commonly used cosmetics are sunscreens. These are formulations that are applied onto the skin surface to protect it from the harmful effects of ultraviolet (UV) light. Repeated exposure of the skin has been associated with a high risk of developing skin cancers. According to cancer research USA, 8 out of 10 cases of melanoma could be prevented through an understanding of the harmful effects of sunlight and how to protect oneself from the harmful rays ( Jou and Tomecki, 2014 ). Of concerns to health agencies around the world is the increase in vacation sunbathing as well as the use of artificial UV sources to induce skin tanning among young whites seeking a darker skin ( WHO, 2017 ).

Sunrays consist of an array of wavelengths ranges that vary in frequency and their energy profiles. The suns electromagnetic spectrum consists of cosmic rays, gamma rays, X-rays, UV rays, microwaves, and radio waves in decreasing order of energy. Among these cosmic, gamma and X rays are effectively filtered out of the earth by the atmosphere and therefore present no potential for causing harm. It is, however, noteworthy that they are the most lethal and exposure would lead to disasters of epic proportions. The UV rays can penetrate the earth' atmosphere as can the rest of the lower energy spectrums. Microwaves and radio waves are not of medical importance as relates to causing skin damage. The focus of this article is thus the UV spectrum of light ( Rezende et al., 2014 ).

The UV light is part of the visible light and spans the wavelength from 100 to 400 nm as shown in Fig. 1 below. The UV spectrum is further divided into three; 290–320 nm (UVB) and 320–400 nm (UVA) ( Moyal and Fourtanier, 2008 , Matts, 2006 ). UVC occupies 100–290 nm of the spectrum; however, it is of no medical importance since it is entirely filtered out by the ozone layer. UVB triggers the production of melanin pigment and stimulates the skin cells to produce a thicker epidermis, resulting in a long-lasting tan. It is also the primary cause of sunburns. The UVA light activates melanin already on the epidermis to produce a short-term tan. It penetrates much deeper into the skin than UVB and can cause long term damage to the skin as well as skin aging characterized by loss of elasticity and wrinkling. Its effects manifest much later compared to the effects of UVB which are acute. UVA light also reacts with skin cells to produce free radicals that are highly active and may indirectly lead to DNA mutations which if unrepaired may lead to cancer ( D’Orazio et al., 2013 ). Individuals with light skin pigmentation suffer comparatively more skin damage from UV because it is relatively easy for UV rays to penetrate the epidermis to damage both keratinocytes and melanocytes in the deeper layers of the epidermis ( Harrison and Bergfeld, 2009 , D’Orazio et al., 2013 , Matsumura and Ananthaswamy, 2004 ).

The electromagnetic spectrum for ultraviolet light. Reproduced from Svobodova et al. (2006) . *Wavelength in nm.

Ultraviolet filters also referred to as sunscreens, are the elements present in photo-protector formulas that interfere directly with the incident solar radiation through absorption, reflection or dispersion of energy ( Schalka et al., 2014 ). They are classified into two categories based on their mechanism of action; Chemical or organic sunscreens and mineral-based or inorganic sunscreens. Chemical sunscreens absorb UV light and convert it into heat energy that is then released from the skin. Typical examples of chemical sunscreens include octisalate and avobenzone ( Gasparro et al., 1998 ). The organic sunscreens afford better aesthetics upon application and are therefore more widely accepted, however they carry the potential for systemic absorption therefore sensitivity and untoward effects are more common with this group of sunscreens. Mineral sunscreens also referred to as sunblocks act by reflecting and scattering the UV light thereby protecting the skin. Common examples of mineral sunscreens include titanium dioxide and zinc oxide. Inorganic filters present a minimum potential for allergic sensitization and high photostability and are therefore more appropriate for people with sensitive skin ( Chen and Wang, 2016 ). However, their reflective properties may cause excessive shine and a whitish aspect, limiting their exclusive use to formulas due to low cosmetic acceptance. The efficiency of inorganic filters is related to the size and dispersion of their particles. Currently, existing formulations frequently contain both chemical and mineral sunscreens. Different formulations exist including creams, gels, sprays, and oils. The choice of which is dependent on individual requirements and preferences ( Schalka et al., 2014 , Robinson, 2017 ).

1.2. Historical perspective of sunscreen use

There is little literature on the way ancient societies used to shield themselves from the sun. However, sunscreens have been used to mitigate the harmful effects of the sun on the skin since medieval time. In ancient Egypt, women applied various natural products as sunscreens. These include; tirmis, yasmeen, zaytoon, sobar, aquatic lotus oil, almond oil, calcite powder and clay, rice bran extracts among many others. The Greek and other communities living in the Mediterranean, having discovered the harmful effects of the sun, designed special hats to shield themselves from the harmful rays ( Trivedi et al., 2017 ). There is documentary evidence of the use of oil using the Greek Olympics ( Cosentino, 2000 ). Other numerous writings indicate a society well aware of the association of extended skin exposure to the sun and the aging or physical changes. Acidified quinine was used in the 1880s to protect a patient with eczema from harmful UV rays ( Urbach, 2001 ).

Clothing in medieval societies was mainly designed to suit the climatic conditions in which the societies dwelt in. Cave drawings in tropical zones indicate that ancient Egyptians used to cover only certain parts of the body while leaving others exposed. Over time the culture evolved to cover the entire body. These ancient beings must have realized that the warmth of the sun was followed by pain inflamed skin. The Indian and Chinese societies are credited with having invented the umbrella which also dates back to medieval times ( Urbach, 2001 ). The legendary King Arthur is pictured with women covered in wimples. The Tibetans used to smear their skin with tar and herbs while the red Indians covered themselves with red ochre for cosmetic reasons probably unaware of the protective effects against the sun. The Burmese society also used plant extracts as cosmetics way back in 2000 BCE ( Goldsberry et al., 2014 ). In East Africa, the Masai community has a long tradition of smearing red ochre on their hair and face for aesthetic appeal but are oblivious of the protection afforded to their skin. Folklore has it that the Kikuyu community in Kenya used to smear clay over their exposed body parts to shield them from the destructive effects of sunrays as they went about their peasantry farming activities ( Ambrose et al., 2016 ).

In modern times commercial use of sunscreens was first reported in 1928 in the USA following the introduction of an emulsion containing benzyl cinnamate and benzyl salicylate. Formulations containing phenyl salicylate appeared in Australia in the early 1930s. Quinine oleate was used in the USA in the mid-1930s. P- Aminobenzoic acid (PABA) was patented in 1943, and numerous sunscreens containing PABA followed this. The US army developed specifications for sunscreens in the 1950s ( Kwan et al., 2014 ).

1.3. Effects of UV exposure on the skin

Ultraviolet (UV) radiation causes both beneficial and undesirable effects on the skin ( Svobodova et al., 2006 ). The purpose of sun protection is to minimize unwanted effects without affecting the beneficial ones. The effects may present acutely while others develop over prolonged periods ( Matsumura and Ananthaswamy, 2004 , Soter, 1990 ). They include tanning, sunburns, photoaging and skin cancer. Tanning refers to the delayed pigmentation of the skin which is considered desirable in many cultures. The practice of cosmetic tanning has gained prominence among young Caucasians with the trend has been increasing with advancements in technologies that make it possible to produce artificial UV light. The WHO has raised the alarm over this practice as it predisposes to skin cancer in the long term ( WHO, 2017 , O’Sullivan and Tait, 2014 ). Sunburns refers to dermal erythema arising due to dilatation of superficial blood vessels is a common occurrence following exposure to UV rays. Extreme exposure causes the skin to become painful and edematous with or without blistering ( Gilchrest et al., 1981 ). The most common forms of skin cancer are; basal cell carcinoma, squamous cell carcinoma, and cutaneous malignant melanoma. The first two are grouped together as non-melanomas and are associated with higher morbidity and cause more extensive aesthetic changes on the skin while higher mortality occurs in the malignant melanoma ( Madan et al., 2010 , Fransen et al., 2012 ). Exposure to UV radiation is considered to be a significant etiological factor for most forms of cancer ( Matts, 2006 , Fartasch et al., 2012 , Surdu et al., 2013 ). Photoaging which includes irreversible changes to the skin has been associated with chronic exposure to the sun. It presents as dry skin, rugged furrows, sagging and loss of skin elasticity ( Cavinato et al., 2017 ). This is in contrast to intrinsically aged skin that is pale, finely wrinkled and appears smooth ( Farage et al., 2008 ).

1.4. Use of sunscreens for protection against ultraviolet-induced skin damage

With the advancements in the medical field as well as science in general that came about in the 20th century, it was demonstrated that the UV section of light contributes significantly towards skin damage. Studies in laboratory rodents enabled greater understanding of UV-induced immune depression, carcinogenesis, photodamage and photoaging ( Gonzaga, 2009 ). Animals irradiated with UV demonstrated lesser hypersensitivity, and they failed to reject organ implants, unlike the controls which were not irradiated indicating a reduction in the immunological capacities of the irradiated animals ( Schalka et al., 2014 ). Scientists also observed that the incidence of melanoma was higher in populations where sunbathing is common. More intensive studies confirmed that those who used sunscreens on a routine basis suffered skin damage to a much lesser extent ( Soter, 1990 ). Widespread research has further characterized the causes of skin cancers, and the numerous cancer agencies have included UV rays as one of the significant human carcinogens ( El Ghissassi et al., 2009 ; Newton-Bishop et al., 2011 ). Public awareness campaigns have since led to greater acceptance and usage of sunscreens. Initial efforts were developed to produce anti UVA products specifically; recently most sunscreens formulations contain both anti-UVA and anti UVB agents ( WHO, 2006 ).

2. Classification of sunscreens and the mechanism of photoprotection

Broadly, sunscreens are classified as either topical or systemic based on the route of administration. Topical sunscreens are further divided into two classes; Organic and inorganic substances based on their mechanism of protection. Inorganic sunscreens are sometimes referred to as sunblocks ( Rigel, 2014 ).

2.1. Organic sunscreens

These are generally aromatic compounds linked with a carbonyl group. They are broadly classified into three categories based on the range of protection; UVB (290–320 nm) and UVA (320–400 nm) and broad-spectrum sunscreens that cover the entire spectrum (290–400 nm) ( Gabard, 2009 ). Examples of organic sunscreens covering UVB include (PABA) and its derivative padimate O. salicylates including octisalate and homosalate, cinnamates including octinoxate and cinoxate, octocrylate, benzsulidone and dibenzoylmenthanes. UVA filters include benzophenones; oxybenzone and sulisobenzone, avobenzone and meradimate, Methyl anthranilanate and ecamsule. Broad spectrum organic filters that cover both UVA and UVB include besoctrizole, silatriazole among others ( Tuchinda et al., 2006 , Serpone et al., 2007 ).

2.2. Inorganic sunscreens

These are particles that scatter and reflect UV rays back to the environment. They act as a physical barrier to indent ultraviolet and UV light. The most commonly used particulate sunscreens are titanium dioxide and zinc oxide ( Serpone et al., 2007 , Dransfield, 2000 ). They are considered broad spectrum as they cover the entire ultraviolet spectrum. The inorganic sunscreens are also referred to as sunblocks, a term coined from their mechanism of photoprotection ( Dransfield, 2000 ).

2.3. Systemic sunscreens

These are sunscreens that are absorbed into the body and accumulate in the skin affording protection from the UV rays. Common examples under this category are shown in Fig. 2 ( Latha et al., 2013 ). The use of systemic sunscreens for daily routine is minimal, as such the focus of this article ison topical sunscreens as these predominate in the market.

Classification of sunscreens. It is adapted from Latha et al. (2013) .

2.4. Mechanism of photoprotection

Sunscreens act by preventing and minimizing the damaging effects of the ultraviolet sun rays following exposure to the sun. Sunscreens have been demonstrated to increase the tolerance of the skin to UV exposure. They primarily work through two mechanisms as detailed below. Fig. 3 gives a pictorial perspective of the mechanisms of action stated.

Scattering and reflection of UV energy from the skin surface. Mineral based (Inorganic sunscreens work primarily through this mechanism. They provide a coating that blocks sun rays from penetrating through the skin ( Dransfield, 2000 ).

Absorption of the UV energy by converting it to heat energy thus reducing its harmful effects and reduce the depth through which it can penetrate the skin. Organic sunscreens work primarily through this mechanism ( Dransfield, 2000 , Lademann et al., 2005 , Manaia et al., 2013 ).

Mechanism of action of organic and inorganic sunscreens. Adapted from Manaia et al. (2013) .

Multiple organic compounds are usually incorporated into chemical sunscreen agents to achieve protection against a range of the UV spectrum. Inorganic particulates may scatter the microparticles in the upper layers of skin, thereby increasing the optical pathway of photons, leading to absorption of more photons and enhancing the sun protection factor (SPF), this results in high efficiency of the compound ( Trivedi et al., 2017 ).

3. Development of sunscreens

The development of sunscreens requires a thorough understanding of the anatomy and physiology of the skin as well as the physical-chemical properties of the substances that one intends to include in the formulation. The stability of the organic substances and the excipients need to be examined as some exhibit instability on exposure to the UV. Inorganic sunscreens generally have limited stability issues as well as limited toxicity ( Tuchinda et al., 2006 , Urbach, 2001 ). The aesthetic appeal of the product must be taken into consideration to promote consumer compliance.

3.1. Properties of an ideal sunscreen

Desirable chemical attributes include; inertness, nonirritant, photostability, and compatibility with other ingredients. Physical characteristics include low viscosity to promote good spreadability, aesthetic appeal, small particle size, waterproof capability, appropriate solubility and non-odorous. Functional attributes include the ability to afford protection across a wide range of wavelength and limited systemic absorption through the skin to minimize sensitization. The products should also be readily available, inexpensive and contaminant free ( Manikrao Donglikar and Laxman Deore, 2016 ).

3.2. Formulation

Formulation of sunscreen involves four critical steps; selection of the target product design, choice of active ingredients and the delivery vehicle followed by product optimization as shown in Fig. 4 . The primary objective of the formulation expert is to develop a product that forms a continuous film on the skin. Penetration of the organic ingredients into the skin should be minimized ( Tanner, 2006 ). Organic sunscreens are formulated as lotions and light ointments. On application, they form a thin film on the skin surface that affords UV protection. Other formulations include oils, gels, emulsions, mousses (fluid emulsions), aerosols, sticks, and powders. Inorganic sunscreens are more difficult to formulate due to their particulate nature. Traditionally, they were formulated as creams that were sticky, oily and unpleasant to use. Nanomization has allowed spray formulations that form a translucent layer on the skin that affords protection while maintaining the aesthetics of the product. Currently no nanomized spray formulations of sunscreens have been approved for registration owing to safety concerns as these nanoparticles may be inhaled and therefore cause system toxicities. Inorganic sunscreens are formulated as pastes, emulsions, sprays, and ointments. Particle engineering approaches including micronization and nanomization of the particles are done to increase the aesthetic value of the products ( Nesseem, 2011 ). The safety and convenience of the user guide the formulation approach. Any substance with potential skin irritancy and potential allergens must be avoided. Like other skin products, formulation requires the inclusion of adhering agents to promote skin adsorption as well as an appropriate vehicle into which the active substance is dispersed. Patents play an essential role in the development process, and careful consideration must be taken before embarking on product development ( Aikens and Dayan, 2016 ).

The process of formulating sunscreen products.

Among the challenges and concerns associated with topical sunscreens formulations involve the photostability of organic filters, broadening the effectiveness spectrum and parameters, incorporating active ingredients, improving cosmetic and sensory aspects, individualizing vehicles. The ideal sunscreen formulation should take into consideration aspects including efficiency for the intended use, the scope of protection spectrum (UVA and UVB), safety and tolerability for topical use, stability, no staining of clothes, adequate cosmetics, pleasant fragrance, resistance to water, spread-ability, high extinction coefficient, and affordable cost. Sunscreen formulations include the main sunscreen agents, excipients specific to the formulation type including an appropriate solvent or vehicle systems. The contents selection is determined by the intended use and the physicochemical nature of the ingredients. Purified water used in product formulation is prepared through reverse osmosis and other established methods of purifying water for industrial use ( Tanner, 2006 , Nesseem, 2011 , Aikens and Dayan, 2016 ).

The most common sunscreen actives; titanium dioxide, zinc oxide, avobenzone, benzophenone 8, octocrylene, and oxybenzone are used. To vary the amount of sun protection, the level of the active ingredient is adjusted. Lademan and group established synergy between organic and organic sunscreens and demonstrated superior efficacy of products comprising of the two compared to those containing only organic or inorganic sunscreens ( Lademann et al., 2005 ). The FDA prescribes the maximum allowable concentration of each ingredient as well as the impurity content. It is common to find sunscreen being co-formulated with other skin products for value addition ( Tanner, 2006 ). A rationally designed and developed product enhances the compliance of the users while affording the necessary protection against the ultraviolet-induced skin damage ( Xu et al., 2016 ).

In the last two decades the adoption of the Quality by Design (QbD) concept has been advocated by the leading regulatory authorities. Embracing this approach includes a scrupulous scientific design of the product, careful selection of materials and process parameters to ensure the achievement of a predefined product quality profile ( Mishra et al., 2018 ). The formulator develops a Quality Target Product Profile (QTTP) that specifies the desired physicochemical and performance attributes of the sunscreen. They then proceed to define the Critical Material Attributes (CMAs) and process parameters required to achieve the QTTP so defined ( Fukuda et al., 2018 ). Risk assessment is conducted to profile areas that may prevent achievement of the desired product quality and appropriate measures are undertaken to address these potential risks. To supplement achievement of the desired product quality, use of design of experiment (DoE) tools could be a valuable guide in optimizing the desirable attributes of the sunscreens ( Peres et al., 2017 ).

3.3. Analysis of the final product

Physicochemical and microbiological characterization of the final product is required to establish its compliance with required quality parameters. The specific tests include the visual analysis, stability testing, pH determination, SPF evaluation, determination of water resistance and its microbiological evaluation.

Physical analysis : Includes organoleptic tests to observe changes in the color, and presence of phase separation in the product.

Stability tests : Colour, phase separation and liquefaction. There should be no color changes nor separation of phases in sunscreen formulations in the stability tests if they are to pass the quality tests. The absence of liquefaction provides strong evidence for the stability of the emulsions ( Abdassah et al., 2015 ). These tests should ascribe to the International Committee on Harmonization (ICH) Q1A-Q1F ( Abraham, 2009 ).

PH determination over time: The pH value of sunscreen stored at different conditions is determined using a digital pH Meter. The pH tests are repeated for multiple emulsions or formulations after a defined period of storage. Ideal pH is around 6.0 which approximates the average PH of the skin. pH changes indicate the occurrence of chemical reactions that indicate the quality of the final product ( Smaoui et al., 2017 ).

Determination of SPF in vitro using spectrophotometry : The in vitro methods are in general of two types. Methods which involve the measurement of absorption or the transmission of UV radiation through sunscreen product films in quartz plates or biomembranes, and methods in which the absorption characteristics of the sunscreens agents are determined based on spectrophotometric analysis of dilute solutions ( Mpiana, 2014 ). A detailed description is given in Section 4.1 below.

Level of water resistance for UVB : This test is conducted by immersion of a volunteer subject in a pool or spa for 40 min with a five-minute rest in between (20-5-20). The procedure is done immediately after the application step described in the SPF determination. To obtain a water resistance label claim of 80 min, four immersions -drying cycles are thus required. After the immersion drying cycles, the SPF determination is then done as per the guidelines. The sunscreen product is considered to be water resistant if it retains no less than 50% of its SPF following immersion ( Patrician Poh Agin, 2006 ).

Microbiological stability : Sunscreens like other topical formulations must be free from any microbial contamination that may render them deleterious to the users ( Smaoui, 2012 ). Common microbiological stability tests for sunscreen products include tests for Streptococcus aureus, Pseudomonas aeroginosa, yeast, and mold. Solutions of the sunscreen product are made an inoculated into the propagation media appropriate for the specific organism being tested, the media is incubated in the at room temperature (25 °C) for specified period after which the number of colonies are enumerated ( Smaoui et al., 2017 ). Preservation systems and strict compliance with good manufacturing practices can mitigate against the introduction of harmful microbes ( Smaoui et al., 2017 ).

Other general quality parameters are formulation type specific and include spreadability, extrudability, texture, viscosity and firmness of gels, creams and lotions, spray characteristics including the spray rate, pattern and droplet sizes, actuation force, spray can leakage among others ( Baki and Alexander, 2015 ).

4. Measurement of the effectiveness of a sunscreen

The effectiveness of a sunscreen is determined by various indices including; Sun protection factor, persistent pigment darkening, immune protection factor among others.

4.1. Sun protection factor

Sun Protection Factor (SPF) refers to the ability of the sunscreen to prevent the development of erythema upon exposure to UV radiation ( Mpiana, 2014 , SPF, 2017 ). The SPF value is mainly determined using in vivo approaches but may also employ in vitro spectrophotometric methods as well as in silico ones that employ computer models to predict the SPF value ( Osterwalder and Herzog, 2009 ). Traditionally in vitro test for SPF determination used excised skin from cadavers or laboratory animals, usually albino hairless mice. SPF can also be determined using spectrophotometric methods ( Mbanga et al., xxxx , Nobre and Fonseca, 2016 , Dutra et al., 2004 ). Current guidelines prescribe use of human volunteers for in-vivo SPF determination. The sunscreen is carefully applied at the rate 2 mg/cm 2 and allowed to dry gradually. The skin areas commonly used are the lower back specifically areas that have not had previous exposure to sunscreens. It is recommended that careful selection of subjects be done with a requirement that they should ideally haven’t had sun exposure or had their skins tanned for at least 90 days prior to enrollment. Other key requirements is lack of skin sensitivity, a Flitzpatrick skin types II, III and IV and who agree to sign an informed consent ( D’Orazio et al., 2013 , Moyal et al., 2006 ). Other elements of inclusion and exclusion criterion follow the guidelines for clinical trials ( Bayer Inc, 2009 , GSK, 2017 ). Detailed guidelines for the in-vivo SPF determination is outlined in the International sun protection Test Method ( ISO, 2010 ). SPF is expressed as the ratio of the minimal erythemal dose (MED) required to induce erythema on the protected skin and that dose required to induce the same on unprotected skin on the same individual ( Osterwalder and Herzog, 2009 ). The mathematical expression is shown in Formula (1) .

Formula 1. Calculation of SPF.

There is a global shift to minimize animal testing in the development of medicines and related products with recent guidelines prohibiting use of animals in experimental studies ( Smith, 2015 ). Notably it has been established that there is a strong in-vitro in-vivo correlation in SPF determination therefore obviating the need for animal studies ( Dimitrovska Cvetkovska et al., 2017 ). As such scientists have developed in vitro techniques that determine SPF. Two approaches have been developed and validated; Measurement of absorption or the transmission of UV radiation through sunscreen product films in quartz plates or membranes and methods in which the absorption characteristics of the sunscreens agents are determined based on spectrophotometric analysis ( Dutra et al., 2004 , Walters et al., 1997 ). The tests are relatively inexpensive and rapid to conduct ( Sudhahar and Balasubramanian, 2013 ). The SPF is related to absorbance as per Formula (2) ;

Formula 2. The relationship between absorbance and SPF ( Walters et al., 1997 ).

Other methods proposed by Mansur et al in 1986 involve spectrophotometric measurement of the absorption characteristics of the sunscreen products may be used with accurate SPF determination ( Dutra et al., 2004 ).

The magnitude of the SPF required for a specific individual is determined by knowledge of the UV climatology, the user’s behavior outdoors and their susceptibility to sunburns ( Autier et al., 1999 ). Different regions have different UV radiation exposures based on their latitudes with the tropics having the highest with the extreme north and south having the least ( D’Orazio et al., 2013 ). The SPF only measures the protection against UVB light. Grading system for SPF ranges from low to high: Low: (SPF 2–15), Medium: (SPF 15–30) High: (SPF 30–50), Highest: (SPF > 50) ( Osterwalder and Herzog, 2009 ). The protection afforded by the sunscreens is usually much less than the SPF indicated due to limited knowledge of their use therefore inaccurate, insufficient and non-uniform application. Recommendations for ideal use include; avoiding sunscreens during the autumn and winter months as there is limited UV exposure. Using sunscreens with SPF above 30 during summer and sunny days is recommended ( Draelos, 2006 ).

4.2. Persistent pigment darkening (PPD)

This measure establishes the ability of the sunscreen to protect against UVA light. The method of determination is similar to that of establishing SPF detailed above ( Moyal et al., 2000 , Matts et al., 2010 , Nash et al., 2006 ). The level of protection is expressed as the UVA protection factor and expressed as the ratio between the minimal dose required to induce pigmentation (MPD) in the protected skin and the MPD observed on the unprotected skin and is calculated as given below. A consistent study protocol is required to minimize the variability of results across multisite laboratories ( Moyal et al., 2006 ). The mathematical expression for PPD determination is shown in Formula (3) below.

Formula 3. Calculation of UVA protection factor.

Subscript p and u indicate the protected and unprotected skin respectively.

4.3. Immune protection factor

The term immune protection factor (IPF) refers to the ability of sunscreen products to prevent UV-induced immunosuppression. IPF is assessed by complex methods such as the ability of a sunscreen to inhibit either the sensitization or elicitation arm of contact or delayed-type hypersensitivity reactions to allergens such as dinitrochlorobenzene (DNCB) and nickel, respectively. IPF is considered to correlate better with the UVA-protectiveness of sunscreen than with its SPF ( Fourtanier et al., 2005 ).

5. Regulatory requirements

Regulatory agencies seek to safeguard the safety and welfare of consumers using cosmetic products based on sound science. Different jurisdictions classify sunscreens as either therapeutic or cosmetic products. The USA, Australia, and Japan consider sunscreen as medicinal products subject to the strict requirement of manufacture under GMP conditions like other drugs. In the USA, cosmetic manufacturers are required to demonstrate the safety of each of the ingredients incorporated into their final products. The regulations also prescribe the maximum amounts of specific ingredients that have known toxicities while also providing a comprehensive list of substances that should not be included in the formulation ( Pirotta, 2015 , Benson, 2017 ). Cosmetic regulation is guided by the federal food drugs and cosmetic act of 1938 ( Pirotta, 2015 , Cavers, 1939 ). The sunscreen innovation act is the latest guide guiding the production of sunscreens and established the framework for approval of the next generation of sunscreens. ( FDA, 2016 ) In the European Union (EU), cosmetic products are regulated under the Cosmetic Regulation (EC) No 1223/2009 which came into implementation in July 2013. The EU regulations are the first in the world to impose a complete ban on testing of cosmetic products on animals. Further the regulations proscribe the marketing of cosmetic products containing ingredient(s) tested on animals ( Pirotta, 2015 ). Sunscreens are considered cosmetic products in the EU; however, the quality requirements are equally high. Regulation in emerging markets and developing countries is variable ( Kaimal and Abraham, 2011 ).

5.1. Safety assessment

Before approval is granted for any sunscreen product, evidence towards its safe use must be established. The safety testing of sunscreen products is included in the laws regulating cosmetic products in general for the respective countries or regional jurisdictions where applicable. Cosmetic safety assessment takes into consideration the physicochemical properties of each ingredient included in the sunscreen formulation, as well as its potential to cause harmful effects over short-term, medium-term and long-term use. The toxicological studies aim to investigate both local and systemic effects. The endpoints generally considered include acute toxicity, repeated dose toxicity, skin and eye irritation, skin sensitization, mutagenicity, carcinogenicity, and effects on the reproductive system. Chemicals that may bear potential carcinogenic, mutagenic, or reproductive toxicity (CMR) or those that may persist and accumulate in the body over time are particularly excluded from use in cosmetic products ( Smith, 2015 ). The US food and cosmetic act CFR 21 which is implemented by the Food and Drugs Administration (FDA) declares that cosmetic products whose safety has not be substantiated prior to marketing be deemed misbranded unless the warning that the safety of the product has not been determined be conspicuously included on the principal display panel ( Benson, xxxx ).

5.2. Labeling requirement

The labeling requirements for sunscreens must comply with the guidelines issued by the specific regulatory authority. Labeling should include the following; Identity of the product and the key ingredients, excipients and their percentage composition. The list of ingredients should be in the order of predominance from the highest to the lowest ( Mancebo et al., 2014 ). The label should include a statement on the name and location of the manufacturer or distributor of the product, cautionary warnings in case a patient is allergic to any of the formulation constituents, optimal storage conditions, appropriate use, frequency, SPF value and Water resistance ( Draelos, 2006 ). The EU cosmetic regulations require that certain ingredients such as nanomaterials to be included in the sunscreen products labelling ( Smith, 2015 ). The EU and the Australia Therapeutics Goods Agency (TGA) do require the inclusion of the products shelf life in the packaging label ( Smith, 2015 , O’Sullivan and Tait, 2014 ). In the USA some sunscreen products do not require expiration dating, this is in circumstances where the manufacturer provides documented evidence demonstrating that the product is stable for no less than 3 years ( FDA, 2018b , Bergeson, 2019 ). The FDA does requires the labelling to include the expiration date for sunscreens where the manufacturer cannot provide the stability data to this effect. A monograph reviewing the regulation of sunscreens comes into effect in the year 2019 ( FDA, 2018b , Food and Drug Administration, 1999 , Sunscreen Drug Products for Pver-the-Counter Human Use, 2001 ).

6. Controversies associated with sunscreens

Oxybenzone is absorbed systemically following topical application as a component of sunscreens. It is excreted in feces and in urine ( Mancebo et al., 2014 ). Studies have demonstrated that oxybenzone has estrogenic and antiandrogenic activity in laboratory animals therefore potential endocrine disorders for long term usage. The dosage units used for these tests were extremely high and the exposure in humans is significantly much lower. Sunscreens have been associated with environmental contamination with oxybenzone, octocrylene, octinoxate being identified in fresh water. Of major concern is the damage caused to coral reefs with oxybenzone being implicated in coral reef bleaching ( Schneider and Lim, 2019 ). Inorganic sunscreens though considered to be relatively safe can pose potential health risks due to their formulation as nanoparticles which may potentially be absorbed systemically. The inhibitory effect of sunscreen on vitamin D synthesis have also been described ( Libon et al., 2017 ). Other studies show that sunscreen use has no effect on the synthesis of Vitamin D ( Hansen et al., 2016 ). More comprehensive studies are required to establish the accurate association between sunscreen use and vitamin D status.

7. Conclusion

Sunscreens are critical products employed as photoprotectants against the harmful UV rays. Increased awareness about the risk of continuous exposure to the sun and its relation to cancer has increased the demand for sunscreens. Health agencies around the world have taken up the interest in advocating for the appropriate use of sunscreens as this has been demonstrated to afford protection against skin aging, tanning, and melanomas. Regulatory agencies across the world are also coming up with the requisite policies to enhance the oversight on manufacture of quality sunscreen product consistent with emerging scientific knowledge.

Pharmaceutical scientists understand the scientific principles of topical drugs and can formulate sunscreens that comply with all requirements for safety, quality efficacy, and consumer acceptance. The formulation of sunscreen continues to evolve with new technologies enhancing product design and efficacy. Incorporation of quality by design concepts in the manufacture of sunscreen products is being embraced as regulatory authorities reassign the classification of sunscreen from general cosmetics to therapeutic drugs.

Peer review under responsibility of King Saud University.

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How does sunscreen work?

Published: 22 October 2024

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https://www.health.qld.gov.au/newsroom/features/how-does-sunscreen-work

You know that sunscreen can help to protect your skin from damage and cancer, but do you know how it actually works and how to find one that works best?

What is a burn?

First things first: to understand how to protect yourself, you need to know what’s burning you and damaging your skin.

It’s not actually the sunlight you can see with your eyes that’s the problem. Instead, ultraviolet (UV) radiation, a type of light humans can’t see, is what damages your skin.

That’s why you can get sunburned on a cloudy day: the visible light might be lessened by the clouds, but some UV radiation can pass right through.

Humans can’t see or feel different levels UV radiation, so it’s not possible to look out the window and decide if today is a day you’ll need sunscreen. You can look up the UV Index on the weather report, but because Queensland’s UV levels are often high year-round, it’s wise to always be sun safe.

UV comes in three types: UVA, UVB and UVC . UVA penetrates deeply into the skin and can cause both DNA damage and premature aging of the skin, including wrinkling and pigmentation changes. UVA can pass right through the ozone layer and through some types of glass .

UVB rays penetrate the top level of skin, called the epidermis. It causes sunburn and can also cause cell damage. Exposure to UVB is a significant risk factor for skin cancer, particularly melanoma. UVB can pass partially through the ozone layer.

When you’re buying a sunscreen, look for a ‘broad spectrum’ sunscreen, which will provide you with protection from UVA and UVB.

UVC is completely blocked by the ozone layer.

How does sunscreen protect your skin?

Sunscreen is more complex than it looks. It’s made up of different ingredients that all protect your skin in different ways. Some reflect the UV rays, so they don’t penetrate your skin, while others scatter them off your skin or absorb the radiation.

The SPF label on your sunscreen bottle gives you an indication of how well the ingredients in that product protect your skin. SPF stands for ‘sun protection factor’ and is a measure of how much protection is offered by the sunscreen. SPF 30+ sunscreen filters 96.7% of UVB rays, while SPF 50+ filters 98%.

Of course, sunscreen will only protect you if you use it correctly: applying it liberally (1 teaspoon per limb or 7 teaspoons for a full body application) on all exposed skin and reapplying every 2 hours.

Why is some sunscreen so sticky or slippery?

Sunscreen needs to stay on your skin to do its job, particularly if you’re swimming or getting sweaty. So, sunscreens, especially water-resistant ones, might feel tacky or filmy on your skin.

There are a range of sunscreens available, some with a ‘non-greasy’ or ‘dry touch’ feel. If the feeling of sunscreen on your skin is going to put you off wearing it, try different options until you meet a product that’s your match, rather than not wearing sunscreen at all.

Make sure you rub sunscreen in well when you apply it, so it can’t just come off if you hit the water or your clothing brushes up against it. Apply sunscreen 20 minutes before you go outside to give it time to bind to your skin.

How do I know if my sunscreen is legit?

There are a lot of different sunscreen products available, so how do you know which ones will protect your skin the best? And more importantly, how do you know which products won’t provide you with proper protection?

The Therapeutic Goods Administration regulates sunscreens that are used as a sunscreen only, and products that have sunscreen in them, like insect repellents or moisturisers. If you want to know if your product has been registered by the TGA, you can search the Australian Register of Therapeutic Goods (ARTG) .

Products included in the ARTG will also have an AUST L number on their label. This label shows that the ingredients used in the sunscreen are all pre-approved, low-risk ingredients.

Cancer Council Queensland recommends using a broad spectrum, water-resistant sunscreen labelled SPF30 or higher, as well as other forms of protection like a broad-brimmed hat, long sleeves, wraparound sunglasses and staying in the shade as much as possible.

How to use sunscreen properly

Start off by reading the instructions on the bottle, as some sunscreens might have different requirements, such as needing to be shaken well before you use them.

Apply at least a teaspoon of sunscreen to each limb, and make sure you rub it in all over.

Have someone help you if you can’t reach spots like your back or shoulders, and make sure you rub sunscreen in places where your clothes might shift, like along the small of your back where it meets your swimmers.

Reapply your sunscreen every two hours, or after each swim, and wait 20 minutes before you jump back in the water.

If you’ve been out in the sun and you’re reconsidering whether you’ll bother to be sun safe, keep in mind that sunburn doesn’t show up straight away . In fact, it can take 4-6 hours for sunburned skin to turn red. So, it’s no use looking in the mirror and thinking, ‘Hey, I’m not red yet, let’s go back out!’ The fact that you don’t look burned yet doesn’t mean your skin hasn’t already copped some damage, and that there won’t be more to come if you’re not practising your Slip, Slop, Slap, Seek and Slide !

This page is tagged in the following topics

• Men's health
• Women's Health
• Children's health

Last updated: 22 October 2024