Trust your sunscreen with caution: A literature review on the side effects of sunscreen

Sunscreen classification

According to how they are administered, sunscreens can be broadly divided into topical and systemic categories^[1] [Figure 2]. A multi-component sunscreen includes both active chemicals to block UV radiation and common coatings to prevent bleaching and color fading.^[4] The formulation of sunscreen can contain a variety of UV filters. They are divided into two groups: synthetic or organic and inorganic or mineral filters. To maximize sunscreen effectiveness, UV filters should typically stay on the surface or in the stratum corneum upper layers.^[5,6] Organic sunscreens fall roughly into three categories: sunscreens that block UV B (290–320 nm), UV A (320–400 nm), and broad-spectrum sunscreens (290–400 nm).^[1]

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Figure 2:

Classification of sunscreen.

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Aromatic ketones, Benzophenones 1, 2, 3, and 4 are only efficient against short-wave UV A radiation and are the most popular UV A organic filters, while sulfur and sodium atoms are components of the benzophenones 4, 5, and 9. Cinnamates are a class of UV B filters; they are present in 90% of sunscreens. Other significant classes of UV B filters include p-aminobenzoic acids and their derivatives, salicylates, camphor derivatives, octocrylene, ensulizole, and urocanic acid. Other frequently used filters include ecamsule, avobenzone, and meradimate.^[5]

Inorganic sunscreen shields the skin by scattering and reflecting UV rays. The size and dispersion of the particles affect their effectiveness.^[1] Inorganic sunscreen filters that can also be found as nanoparticles include titanium dioxide and zinc oxide. Nanoparticles have photocatalytic characteristics resulting in their photo passivation, which prevents any oxidative stress on the skin or from losing its protective features. Typically, an inert mineral coating of aluminum hydroxide or silica is precipitated on the surface of these nanoparticles. Moreover, sunscreen also has preservatives such as methylisothiazolinone. Systemic sunscreens are rarely used, even though they provide UV protection.^[1,5,7]

Evaluation of a sunscreen’s effectiveness

Sun protection factor, persistent pigment darkening, and immune protection factor are the three basic measures used to assess the efficacy of sunscreen. A sunscreen’s sun protection factor measures how well it can prevent erythema from developing after exposure to UV rays. Sun protection factor ratings measure the effectiveness of protection and specify how long they will shield the user from UV rays. Undoubtedly, the sun protection factor numbers are often between 6 and 10, 15 and 25, and 30 and 50 and 50+, respectively, denoting poor, medium, high, and extremely high protection.^[1,8]

However, the Japan Cosmetic Industry Association developed the in vivo persistent pigment darkening method in 1996 to evaluate the UV A effectiveness of sunscreen. Sunscreens with a PA+ grade offer little protection, especially because they only have two to four UV A filters. PA++-rated sunscreens that display significant UV A blocking have four to eight sunscreen ingredients present in them. On the other hand, the PA+++ and PA++++ classifications signify products with a high level of sunscreen effectiveness and more than eight UV A filters.^[8]

Immune protection factor describes a sunscreen’s capacity to stop UV-induced immunosuppression. It is evaluated using sophisticated techniques such as the capacity of a sunscreen to block either the sensitization or elicitation arm of immediate or delayed-type hypersensitivity reactions to allergens such as nickel and dinitrochlorobenzene, respectively.^[1]

Sunscreen benefits

Sunscreen is essential for reducing the prevalence of UV-induced skin issues in individuals, such as the production of reactive oxygen species, erythema, edema, inflammation, premature skin aging, dryness, sunburn reactions, photosensitivity, pigmentation, skin cancer, and other adverse effects^[3,8-11] [Figure 3].

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Figure 3:

Damage caused by ultraviolet rays on skin.

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UV A is the main cause of photoaging because it has a longer wavelength and hence has deeper dermal penetration than UV B, which is mostly absorbed by the skin’s epidermis. The dermis of the skin is exposed to 9–14% of solar UV B radiation. Skin photoaging, which includes wrinkles, laxity, blister, roughness, and loss of skin tone, is largely caused by radiation^[11,12] [Figure 4]. Two sunscreen components, photolyases, and antioxidants have also been shown to prevent and possibly even reverse the effects of photoaging.

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Figure 4:

Action of ultraviolet rays.

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Sunscreen has been shown to reduce melanoma and nonmelanoma skin cancers. Sunscreens usage evidence also indicates a reversal of extrinsic aging. In comparison, sunscreens’ benefits in preventing skin cancer outweigh any short-term changes to the epidermal barrier.^[2,12,13]

Emerging technologies such as Sunsphere and Microencapsulation have led to further advancement of sunscreen. Sunspheres are sun protection factor enhancing vehicles. They are created using water-filled, UV radiation-resistant styrene/acrylate copolymers. It is a hollow capsule that scatters the light that enters it. It increases the sun protection factor by 50–70% and seemed to have improved spreadability, in vitro sun protection factor, and water resistance.^[10,14]

Microencapsulation helps us to reduce the adverse effects of UV filters by preventing direct contact with skin and transcutaneous entry. By microencapsulating, the organic UV filters like octyl methoxycinnamate and butyl-methoxydibenzoylmethane into a microporous zeolitic imidazole framework were able to produce sunscreens that are long-lasting, safe, fluorescent, and stable. We consider their use to be crucial given all the potential uses mentioned above.^[15]

Sunscreen risks

Despite sunscreen being beneficial, its use poses risk to humans. Some sunscreen ingredients are potential carcinogens and endocrine-disrupting chemicals such as benzophenone-3 which is harmful to developing embryos and fetuses as they can interfere with hormones, neurotransmitters, and growth factors crucial for normal development. It has been found to penetrate the blood-placenta barrier which causes worry in pregnant women. Male fertility may be at risk since it can imitate progesterone’s effect on human spermatozoa. Another ingredient, octocrylene, may operate as a barrier to the calcitriol’s function, leading to abnormal vitamin D production in the body.^[16,17]

There is growing evidence that certain endocrine-disrupting chemicals can affect renal function and cause cumulative renal damage too. In addition, studies have shown that some UV filters can be discovered in urine. Sunscreen compound, octinoxate, has antiandrogenic action, which indicates a risk to reproductive organs exposed in utero. The importance of benefits and risks associated with sunscreen use plays a critical role in creating awareness in the population^[6,18,19] [Figure 5].

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Figure 5:

The risks and benefits of sunscreen.

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Absorption of sunscreen ingredients

The possibility that UV filters could pass through the skin and enter circulation sparked questions about the potential harm that UV filters might do to the human body. Even low penetration rates may result in a significant amount of sunscreen entering the systemic circulation. Benzophenone-3, camphor, and octyl-methoxycinnamate exhibit this effect and could produce allergies or phototoxic results.^[20,21] For instance, clinical trials have shown sunscreen ingredients such as oxybenzone, octocrylene, and ecamsule to have high systemic absorption than advised standards.^[2] 0.5 ng/mL in the blood was approved as the regulatory threshold for sunscreen active ingredients by the Food and Drug Administration.^[22]

Researchers also found that oxybenzone was absorbed at a level of 258.1 ng/mL when it was applied to the skin every 2 h as directed on the bottle, this was 516 times more than the advised limit when it was applied to the skin every 2 h as directed on the bottle.^[6] Bloodstream absorption by ingredients depends on a number of factors, such as the active ingredient’s physicochemical properties, the formulation’s features, and the stratum corneum’s thickness and structure.^[22]

After applying sunscreen containing 4% benzophenone-3 for 48 h, the average amount of benzophenone-3 excreted in urine was 11 mg/mL, demonstrating significant skin permeability. Avobenzone and octocrylene were found in more than 20% of urine samples, and the lipophilic UV filter octocrylene and its metabolite 2-cyano-3, 3-diphenylacrylic acid showed substantially slower clearance.^[22] Physical sunscreens are not absorbed into the body like chemical sunscreen components. Less than 0.03% of zinc nanoparticles, according to an in vitro investigation, entered the stratum corneum’s top layer.^[2] It is vital to consider how encapsulation techniques, in addition to formulation components, may affect how well sun filters are retained and absorbed by the skin.^[23]

Each ingredient and their related adverse reactions

Sunscreens help in protecting our skin, but there are reports of adverse reactions due to certain compounds in them which are being researched. There are concerns about its safety as cellular damage and biological changes challenge its potency on a daily basis. Their toxicities include hormonal imbalances, allergic reactions, increased oxidative stress, and phototoxic events.^[6] These UV filters and their coating compounds have been observed to cause a varying spectrum of clinical manifestations which have been reviewed in this literature review.

Octocrylene – chemical formula: C₂₄H₂₇NO₂

Octocrylene absorbs primarily UV B and short UV A wavelengths. Cutaneous side effects such as skin irritation, sensitization, and photosensitization are seen. However, in humans, the irritant reactions to octocrylene are uncommon, whereas sensitization and photosensitization are more prevalent. Photoallergic contact dermatitis to octocrylene is much more frequent in adults than in children.^[29]

Adverse reactions on use of sunscreen could result in irritant contact dermatitis, allergic contact dermatitis, phototoxic, and photoallergic reactions on the face, anterior neck, and dorsum of hands [Figure 6].^[26] The severity of the clinical reaction depends partly on the area of exposed skin.^[27] A study done by Matta et al., showed that the active constituents (avobenzone, oxybenzone, octocrylene, and ecamsule) of four commercially available sunscreens indicated side effects that were rash, milia, lip swelling, pruritus, chapped lips, and eye irritation.^[29] Since occlusive mask donning for healthcare workers during COVID- 19 was mandatory, a letter to editor, Kaul et al. (2020) have supported the potency of topical applications such as sunscreens to become an irritant to cause side effects such as contact irritant dermatitis due to the chemical agents present in them. Furthermore, it can cause changes in skin flora and potential of hydrogen, which can aggravate preexisting dermatoses such as atopic dermatitis and predispose to bacterial folliculitis.^[30] Sunscreen use is currently widespread to the face on a regular basis and causes sensitivity issues when it comes into contact with the eyes. Furthermore, there is still a scarcity of ocular sunscreen products.^[31] Many natural compounds, such as lignin, flavonoids, aloe vera, shea butter, and others are effective in protecting our skin from these rays. They also have high antioxidant capacities and a variety of other advantages over synthetic ones.^[32] Hence, it is important for us to take the aspects of formulation and effectiveness into account as it holds significant benefits if generated in an optimal manner with organic or low-risk damage-causing ingredients.

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Figure 6:

Side effects of sunscreen.

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Limitation

This overview may be subject to a number of restrictions such as only two main electronic databases, PubMed, and Google Scholar which were used. Hence, further important studies might have gone unnoticed. Second, we considered most of the literature reviews that looked into the adverse reaction, side effect, toxicities, absorption, and safety of sunscreen and took only those that had free full texts that were also available in EN languages. However, papers featuring animal experiments and those without a free full-text option were not included as we have focused on side effects occurring in humans following the sunscreen use. Evidence indicates not many toxicity studies on humans or earlier study investigations on this subject which points to lack of research evidence as well as statistical analysis data not being readily available.