Sunscreen: FDA regulation, and environmental and health impact

Shanthi Narla * and Henry W. Lim
Department of Dermatology, Henry Ford Health System, Detroit, MI 48202, USA. E-mail: shanthi.narla1@gmail.com

Received 3rd September 2019 , Accepted 18th November 2019

First published on 22nd November 2019


Photoprotection, including the use of sunscreen, has been shown to decrease the development of keratinocyte cancers and melanoma. Due to concerns about the environmental effects of some organic UVR filters, several locations across the world have begun to pass legislation banning the use of these ingredients in sunscreens. Furthermore, the health effects of several organic UVR filters have also been called into question and a recent proposal by the US FDA has resulted in public confusion about the safety of sunscreens. The aim of this article is to discuss FDA regulation of sunscreens and to review the environmental and health effects of oxybenzone and octinoxate. Ultimately, as dermatologists, our recommendations are to continue to encourage people to practice proper photoprotection including photoprotective clothing, staying in the shade while outdoors, and applying sunscreen to exposed areas. For those concerned about the potential environmental and health effects of organic UVR filters, inorganic/mineral UVR filter (namely, zinc oxide and titanium dioxide)-based sunscreens can be used.


Introduction

In 2018, Hawaii became the first state in the US to pass the law banning sales of sunscreens containing oxybenzone (benzophenone 3, BP-3) and octinoxate (ethylhexyl methoxycinnamate, EHMC), ultraviolet radiation (UVR) filters found in nearly three-quarters of sunscreens currently on the US market, due to concerns of coral reef bleaching. Similarly, Key West, Florida, has also followed suit making it the first city to ban the sales of such sunscreens. The ban in Hawaii and Key West will become effective starting January 2021. In June 2019, the US Virgin Islands also banned sunscreens containing oxybenzone, octinoxate and octocrylene; the ban will be effective from March 2020. Legislations for similar bans have also been approved in Palau, Bonaire, and the nature reserve areas in Mexico. A similar ban is being actively discussed in Brazil and the European Union (EU).

Because of the extensive use of sunscreens (frequent application covering a large body surface area), the US Food and Drug Administration (FDA) has requested in a proposed rule, released on February 26, 2019, that additional safety studies be conducted on 12 of the commonly used organic UVR filters in the US.1,2 In a recent study by scientists at the US FDA on the percutaneous absorption of 4 UVR filters (avobenzone, oxybenzone, octocrylene, and ecamsule), participants were randomized to 1 of 4 sunscreens: 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. The authors found that these sunscreen ingredients can be detected in serum under maximal use conditions in human subjects.3 It should be emphasized that authors concluded that “these results do not indicate that individuals should refrain from the use of sunscreen”.

Excessive sun exposure has been well-recognized to be associated with development of keratinocyte cancers and melanoma, and the use of sunscreen has been shown to decrease their development.4,5 The above concerns have resulted in public confusion on the use of sunscreen as one of the components of photoprotection strategy. This article will discuss the regulation of sunscreen ingredients in the US and review the effects of oxybenzone and octinoxate on the environment and health.

US FDA regulation of sunscreens

In order to completely understand the current state of sunscreens and their effects, a review of regulation of sunscreens is necessary. The US FDA regulates sunscreens as over the counter (OTC) drugs rather than as cosmetics, in contrast to how they are regulated in many other parts of the world.6 Currently, there are a total of 16 UVR filters that are listed on the FDA monograph; in addition, another UVR filter, ecamsule, is available to be marketed as a specific product as this was approved through a New Drug Application process. The FDA has requested additional data on another 8 filters that have applied for approval through the Time and Extent Application (TEA) process and are still pending the approval of the FDA; it should be noted that many of these are widely used in other parts of the world.7 Therefore, there are fewer filters that are available in the US as compared to those in other countries.

In the new FDA proposed rule, the existing 16 filters are classified into three categories: category I, GRASE (generally recognized as safe and effective), which are zinc oxide and titanium oxide; category II, not GRASE, which are para-aminobenzoic acid and trolamine salicylate; and category III, insufficient safety data to determine GRASE status, which are cinoxate, dioxybenzone, ensulizole, homosalate, meradimate, octinoxate, octisalate, octocrylene, padimate O, sulisobenzone, oxybenzone, and avobenzone. Currently, the FDA is seeking additional safety data on the 12 category III filters, although it does not consider them unsafe at this time. As mandated by the Sunscreen Innovation Act of 2014, the FDA is required to issue a final sunscreen monograph within 5 years (i.e. by November 26, 2019).1,2

Endocrinological concerns of sunscreens

Oxybenzone has been found to have adverse endocrinological (hormonal) effects in fish and rats.8–10 In laboratory fish, it (i.e. oxybenzone) has been shown to have antiandrogenic and antiestrogenic effects resulting in decreased egg production and egg hatchings, but at concentrations significantly higher than those previously measured in the environment.11 In rats, a dose-dependent increase in the weight of the uterus was observed when these animals were given high doses of oxybenzone (≥1500 mg kg−1 d−1) in their powdered feed.10 It should be noted that the estrogenic effect detected in this study was very minimal – less than 1 million-fold of estradiol, the positive control used. Nevertheless, this study performed in rats has resulted in considerable public concern.

A literature review conducted in 2013 examined the theory vs. reality of sunscreen application. Determination of SPF of sunscreens is done using a concentration of 2 mg cm−2. However, investigations showed that sunscreen under real-life conditions was applied with concentrations ranging from approximately 0.39 to 1.0 mg cm−2.12 Studies in an Australian population demonstrated that the median quantity of sunscreen applied was 0.79 mg cm−2,13 whereas sunbathers in Denmark applied on average 0.5 mg cm−2.9,14 Using the above information, a study performed by Wang et al. in 2011 demonstrated that the years of daily sunscreen application required by an average US woman to reach systemic levels of oxybenzone equal to those given to the immature rats per unit of body mass ranged from 34.6 years to 277.0 years, depending on the total body surface area of sunscreen application and concentrations of sunscreen applied; these are clearly unattainable amounts of sunscreen exposure in a person's lifetime.15 Short-term studies that have evaluated topical application of UVR filters including oxybenzone in humans have found no significant UV-filter-related adverse effects on reproductive or thyroid function.15–18

Because of known real-life underapplication of sunscreens, recommendations have been made to use sunscreens with higher than SPF30–50 to provide adequate photoprotection. It should be noted that higher SPF sunscreens contain higher concentrations of UVR filters compared to those with lower SPF. This is a factor that needs to be considered in balancing the photoprotection and concerns for environmental impact.

Environmental concerns of sunscreens

There have also been rising concerns regarding the environmental effects of commonly used organic UVR filters, including oxybenzone, 4-methylbenzylidene camphor (4-MBC), octocrylene, and octinoxate. Many wastewater treatment plants worldwide including Brazil, Switzerland, Korea, China, Japan, Thailand, and the US have demonstrated that it is very difficult to remove organic filters from wastewater due to the low water solubility and high lipophilic properties of UVR filters.19–24 Furthermore, in in vitro studies, oxybenzone has been shown to cause bleaching of coral reef, inducing ossification and the deformation of DNA in the larval stage.25 In the same study, concentrations of oxybenzone in seawater were measured at various locations including Hawaii and the US Virgin Islands; levels ranging from 0.8 μg L−1 to 1.4 mg L−1 were detected. This study also reported that in vitro, the coral cell median lethal concentration of oxybenzone for 7 different coral species ranged from 8 to 340 μg L−1 over 4 hours of exposure.25 These concerns are what led Hawaii to pass legislation against the sale and distribution of sunscreens containing oxybenzone and octinoxate. The bill was signed into law by the governor on July 3, 2018, and will take effect in January 2021.17 Key West (Florida), US Virgin Islands, Palau, Bonaire, and nature reserves sites in Mexico have also passed similar bans. A similar ban is being actively discussed in Brazil and the European Union.

In contrast, recent studies have demonstrated differing results. In a study performed by Mitchelmore et al., the concentrations of 13 UV-filters were measured in surface seawater, sediment, and coral tissues from 19 sites in Oahu, Hawaii. The range of mean surface seawater concentrations for oxybenzone was measured as 0.1 to 136.2 nanograms per L (parts per trillion), compared to the median lethal concentration of oxybenzone in the previously mentioned study ranging from 8 to 340 micrograms per L (parts per billion).26 In a study conducted by Du et al., the acute toxicity and potential ecological risk of UVR filters BP-3 and BP-4 (sulisobenzone) on Chlorella vulgaris, Daphnia magna, and Brachydanio rerio were analyzed. Results showed that the induced predicted no-effect concentrations of BP-3 and BP-4 (1.8 × 10−3 and 0.47 mg L−1) were higher than the concentrations detected in the environment at present (3.63–164 and 62.00–574.00 ng L−1), further suggesting that BP-3 and BP-4 remain low-risk chemicals to aquatic systems.27

It must also be considered that warmer water temperature itself can also result in coral bleaching. Cheng et al. demonstrates that recent observation-based estimates show rapid warming of Earth's oceans over the past few decades, contributing to rising sea levels, destruction of coral reefs, declining ocean oxygen levels, and declining ice sheets.28 When the water becomes too warm, corals will expel their algae causing the coral to turn completely white (hence, the term coral bleaching). In addition, repeated thermal stresses can decrease resiliency resulting in significant bleaching-mediated decline, particularly through the depletion of larval recruitment.29,30 In 2016, a report on the coral bleaching of the Great Barrier Reef demonstrated that this phenomenon occurred in remote areas with infrequent human contact. The warming of the ocean water was determined to be the major cause.31 Central equatorial Pacific has experienced 8 severe (>30% bleaching) and 2 moderate (<30% bleaching) events since 1960, each coinciding with the extreme heat associated with El Niño.32

Other factors that need to be considered are bioaccumulation and biomagnification. Bioaccumulation is a phenomenon by which levels of chemicals become higher in organisms over time through exposure to their environments, whereas biomagnification refers to the idea that chemical levels become higher and more concentrated as one moves up the food chain. In Switzerland, white fish, roach, and perch were found to have low but detectable levels of UVR filters, mostly 4-methylbenzylidene camphor (4-MBC; enzacamene).33 In Norway, cod livers also contained UVR filters with octocrylene being the most commonly identified filter (80% of specimens) followed by oxybenzone (50% of specimens).34 Despite the levels of UVR filters being low in fish, Brausch and Rand examined bioaccumulation and found that oxybenzone levels were actually higher in fish than in water.21 Furthermore, the chemicals found in lower-order organisms are not broken down or removed. Thus, when a higher order animal ingests these lower order organisms, it may demonstrate higher and more concentrated chemical levels, hence the concept of biomagnification, which suggests possible negative implications for humans who ingest seafood. However, no clear adverse effects in humans have been reported so far.35

Safety of inorganic filters

In vitro studies have demonstrated that uncoated zinc oxide (zinc oxide particles are coated in sunscreens) can cause rapid bleaching of coral; in contrast, titanium oxide caused minimal changes.36In vitro studies of zinc oxide and titanium oxide nanoparticles have also shown to generate reactive oxygen species, leading to toxicity of cells.37 Neurotoxicity has been a concern in in vitro and in vivo murine experiments with titanium oxide.38,39 However, it should be stressed that when used in sunscreen products, nanoparticles are coated (usually with silica), preventing the release of reactive oxygen species to the microenvironment. Based on currently available data, inorganic UVR filters have few to no health concerns in humans.40–42

Conclusion

While concerns have been raised about the environmental impact of UVR filters, current data demonstrate that the levels in ocean water are at least a thousand-fold lower than that found to be lethal to coral reefs in vitro.26 It is also important to note that organic UVR filters (e.g. oxybenzone and octinoxate) are used in numerous personal care products such as cosmetic items, fragrances, and flavors and are also used as photostabilizers in plastics. Many of the excellent, photostable broad-band UVR filters available in many parts of the world are not yet approved by the US FDA, making it more challenging for manufacturers to replace oxybenzone for products marketed in the US. It should also be noted that while concerns about endocrinologic/hormonal effects have been raised by in vitro and animal studies, no adverse human systemic effects have been reported with any of the UVR filters, which have been widely used since the 1970s.

The adverse effect of excessive UV exposure is well known. Therefore, photoprotection, which includes staying in the shade while outdoors, wearing photoprotective clothing, wide brimmed hat and sunglasses, and applying sunscreen on exposed areas only should continue to be emphasized. For those who are concerned, the use of inorganic/mineral filter (zinc oxide or titanium dioxide)-based sunscreens can be recommended. Individuals practicing vigorous photoprotection should take vitamin D supplementation (600–800 IU) daily.43

Abbreviations

BP3Benzophenone 3 (oxybenzone)
FDAUS Food and Drug Administration
GRASEGenerally recognized as safe and effective
4-MBC4-Methylbenzylidene-camphor, enzacamene
EUEuropean Union
UVRUltraviolet radiation
EHMCOctinoxate, ethylhexyl methoxycinnamate

Conflicts of interest

HWL is an investigator for L'Oréal, Estee lauder, Ferndale, Unigen, and Incyte, consultant for Pierre Fabre and ISDIN, and has served as a speaker in educational sessions sponsored by Pierre Fabre and Eli Lilly. SN is a sub-investigator for L'Oréal and Incyte.

Acknowledgements

A special thanks to Dr. Alexis B. Lyons for providing the graphical abstract image.

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