Sunscreens and Photoaging: A Review of Current Literature

Linna L. Guan; Henry W. Lim; Tasneem F. Mohammad

Disclosures

Am J Clin Dermatol. 2021;22(6):819-828. 

In This Article

Challenges and Limitations of Current Sunscreens

Sunscreen technology has made great advancements in accessibility, consumer acceptability, and overall safety and efficacy over the years. However, the challenges and limitations of current sunscreens leave room for further research and innovation. In the evaluation of sunscreens available for US consumers today, FDA regulations, safety in humans, and safety for the environment must be carefully considered.

In the 2019 proposed rule on sunscreens, the FDA proposed to categorize sunscreen filters as category I—"GRASE" (Generally Recognized as Safe and Effective), category II—non GRASE, or category III—requires further evaluation (Table 1).[41] Currently, only two UV filters are category I: titanium dioxide and zinc oxide.[42] Both of these inorganic filters work by scattering, reflecting, and absorbing UV. The aggregation of these particles on the skin means they tend to leave a whitish hue on the skin that is unacceptable for many consumers, especially those with skin of color.[43,44]

In the 2019 FDA-proposed rule, two ingredients, paraaminobenzoic acid (PABA) and trolamine salicylate, were classified as category II and banned from products marketed in the USA given their safety concerns. PABA has been linked to cases of allergic and photoallergic dermatitis and is a cross-sensitizer to sulfonamide antibiotics, thiazide diuretics, local anesthetics, and dyes.[42] Trolamine salicylate is a salicylate class of UV filters and has been linked to systemic absorption and increased risk of bleeding and salicylate toxicity.[42] It should be noted that neither of these has been used in the US market for years, so this categorization does not affect the US market.

Organic UV filters, dioxybenzone, sulisobenzone, oxybenzone, avobenzone, cinoxate, octinoxate, octisalate, homosalate, padimate O, ensulizole, meradimate, and octocrylene have now been categorized as category III, which means that additional data to determine the general recognition of safety is needed.[42] Organic UV filters absorb the higher energy of UV rays and emit a lower thermal energy.[41,45] It should be noted that the FDA is only requesting safety data for these 12 filters and did not question the efficacy of UV filters. None of the 12 category III UV filters offer effective visible light protection, and only meradimate and avobenzone offer partial UVA1 protection.[41]

The organic UV filters can be categorized into cinnamates, benzophenones, salicylates, PABA derivatives, and others. Octinoxate, a cinnamate, is the most common sunscreen ingredient in the USA. It is photolabile and is often combined with other UVB absorbers to increase both its final SPF and its photostability.[46]

The benzophenones include dioxybenzone, sulisobenzone, oxybenzone, and avobenzone, with oxybenzone the most commonly used agent in the group.[46] Although benzophenones have been shown to be effective UVA filters, their lack of photostability requires them to be compounded with other filters such as octocrylene, salicylates, micronized zinc oxide, and titanium dioxide to improve their photostability.[44,46,47] Additionally, oxybenzone is the most common photoallergen of the UV filters.

The salicylates octisalate and homosalate are only weak UVB absorbers and are mainly used in sunscreens as photostabilizers in combination with other organic filters.[46] Padimate O is a PABA derivative; like its predecessor, it has potent UVB filtration but is rarely used.[44,46] Ensulizole is primarily a UVB filter with minimal UVA2 activity.[48] Meradimate is a weak UVA blocker and has no activity against UVB.[41,46] Octocrylene is a photostable UVB and UVA2 filter primarily used as a photostabilizer in conjunction with other filters.[46] Ecamsule (Mexoryl SX) is an effective UVA filter that has been shown to be effective against photoaging when combined with UVB filters.[49] It has been approved via the new drug application process, with its use as an active ingredient permitted only in certain products under specific concentrations.[41,43,44]

Although other photostable and more effective broad-spectrum UV filters, including bemotrizinol, bisoctrizole, and drometrizole trisiloxane, are available in other countries, these agents—along with many other UV filters available in other countries—are still pending FDA approval in the USA.[27,41] In over a decade, no new UV filters have been approved by the FDA to be added to the 16 currently approved filters. In contrast, the European Commission currently has 27 approved UV filters.[27] However, with the Coronavirus Aid, Relief, and Economic Security (CARES) Act signed into law in March 2020, the FDA has been mandated to move from a laborious rulemaking process to an administrative order process, which means it should not take as long to implement a monograph. The FDA is to issue a new proposed administrative order by 27 September 2021. Once the final administrative order has been enacted, industry has 12 months to comply. In addition, the CARES Act also incentivizes innovation by providing an 18-month exclusivity period to the requesting manufacturer of a new filter.[50]

Controversy regarding organic sunscreen safety in humans has increasingly been a topic of discussion after studies showed systemic absorption of six commonly used sunscreen active ingredients.[51,52] This 2020 study of 48 randomized participants applying 2 mg/cm2 of sunscreen product to 75% of body surface areas between one and four times per day for 4 days demonstrated systemic absorption of avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate.[51] However, a systematic review of 29 studies looking at the effects of two of the most commonly studied sunscreen ingredients—oxybenzone and octinoxate—demonstrated that oxybenzone had no adverse effects on male and female fertility, female reproductive hormone levels, adiposity, fetal growth, childhood neurodevelopment, or sexual maturation, and octinoxate had no effect on thyroid and reproductive hormone levels.[53] Although the review recommended further research into the effects of oxybenzone levels on thyroid hormone, testosterone level, kidney function, and pubertal timing, the evidence is not yet sufficient to support a causal relationship between the elevated systemic levels of oxybenzone or octinoxate and adverse health outcomes. Further longitudinal randomized controlled studies should be performed before factoring the biological effects of systemically absorbed agents into clinical and practical guidelines.[54,55] A recent report by Valisure LLC, an independent laboratory, also raised safety concerns regarding benzene in sunscreen products. After testing multiple batches of 69 brands of sunscreen and after-sun skincare products, they found that 78 batches contained elevated levels of benzene, a carcinogen known to cause leukemia and lymphoma.[56] It is important to note that both organic and inorganic sunscreens and some cosmetic products that did not contain any UV filters were among the contaminated products. In addition, many sunscreen products tested did not contain benzene. The report concluded that the contamination was due to supply chain issues in the manufacturing process rather than degradation of sunscreen filters. These findings led to an FDA citizen petition for the recall of identified batches of sunscreen with elevated levels of benzene and further investigation into these products and their manufacturing processes. A full report, including a list of products tested, can be found on the Valisure website.[57]

Additionally, the National Oceanic and Atmospheric Administration identified ten sunscreen ingredients as being toxic to coral and marine life: oxybenzone, benzophenone-1, benzophenone-8, PABA, 4-methylbenzylidene camphor, 3-benzylidene camphor, nano-titanium dioxide, nano-zinc oxide, octinoxate, and octocrylene.[58] Studies that demonstrated marine toxicity were performed in vitro with high concentrations of sunscreen ingredients.[44,55,59] In a review looking at all 32 published studies until June 2020, 14 different organic UV filters in seawater near coral reefs were detected in the nanograms per liter range, in contrast to toxic levels in the micrograms per liter to milligrams per liter range reported in nine papers.[60] This puts the toxic levels of organic UV filters at 1000- to 1 million-fold higher concentrations than currently reported. Although 27 of the 32 reviewed studies showed no risk of UV filters to coral reefs, three studies of oxybenzone and octinoxate demonstrated a few data points where some risk was present.[54] This reflects the major data gaps that immediately need to be addressed with high-quality monitoring and toxicity studies applicable to the real world. To address this issue, on 9 February 2021, the National Academies formed a committee sponsored by the Environmental Protection Agency to study the environmental and health impacts of sunscreens. Although data supporting that the coral reefs are adversely impacted by environmental exposure to UV filters are limited, the state of Hawaii banned sunscreens containing oxybenzone and octinoxate in 2018, and Key West, Florida, USA, did the same in 2019.[59]

Although FDA guidelines aim to protect US consumers from harm, it has also greatly diminished the variety of UV filters available to consumers. Newer and more effective broad-spectrum UV filters are available in other countries but are not currently FDA approved.[41] With the new proposed administrative order under the CARES Act and careful consideration of human safety, environmental safety, photostability, and consumer cosmesis, the development and approval of new sunscreens that are effective against UVA, UVB, and VL must be considered for protection against photoaging.

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