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Risques de l'oxybenzone.

Why doesn't Typology use oxybenzone?

It is becoming increasingly common to see sunscreens with claims of being oxybenzone-free or formulated without oxybenzone. Laws prohibiting its use have been adopted in many countries. But why is oxybenzone being excluded from many sunscreen formulas, including those of Typology?

Oxybenzone: What is this popular sunscreen filter?

The benzophenone-3 (2-hydroxy-4-methoxybenzophenone; BP-3), commonly known as oxybenzone, is an organic chemical compound (MW = 228.24 g/mol) that belongs to a large family of natural compounds found in plants, such as the family of tropical shrubs, the Guttiferae. Although it is present in plants, most of the BP-3 used today is synthetically created through the Friedel-Crafts reaction of benzoyl chloride with 3-hydroxyanisole, and it appears in the form of crystals or a white to off-white or light yellow powder that is highly soluble in most organic solvents.

It has been widely used as a broad-spectrum chemical UV filter in sunscreens for over 30 years to protect the skin and hair from damage caused by ultraviolet rays, particularly from UVA-II and UVB (cancer, sun spots, blemishes, wrinkles). In Europe, the authorized concentration of oxybenzone in sunscreens is currently limited to 6% for safe and effective use. It is also approved as a UV filter in the United States, Canada, Australia, and several ASEAN countries. BP-3 can also be used as stabilizers to prevent photodegradation in many products.

Scientifically speaking, BP-3 absorbs both long and short ultraviolet rays from the spectrum, ranging from about 270 to 350 nm, which results in an increased energy state called photochemical excitation due to the presence of several chromophore groups. When returning from this elevated state to its ground state, the absorbed energy results in the emission of a longer wavelength radiation that is less harmful than UV rays. This process reduces the amount of harmful UV rays penetrating the skin, as well as the risk of DNA damage.

Oxybenzone, a risky sunscreen filter?

However, controversies have arisen around this ingredient. It raises two main concerns, besides allergic reactions: the fear that it may be an endocrine disruptor, and that it could be harmful to marine life and coral reefs, even though numerous scientific groups and regulatory bodies, including the FDA and the CIR, have reviewed benzophenone-3 and have asserted that it is safe for human health when used as an ingredient in sunscreens at the mandated concentration.

These controversies stem from concerns that have been raised about the relative ease with which oxybenzone is absorbed by the skin and into the bloodstream, at a rate of 1 to 2%, following topical application. Similarly, traces of oxybenzone have been found in urine samples, with quantities ranging between 0.4% and 2%. But does finding a measurable amount of BP-3 in urine mean that BP-3 levels have a detrimental effect on health? In light of such findings, countless studies on the potential dangers of benzophenone-3 have emerged.

After being applied topically, this compound is absorbed by the skin, metabolized and/or excreted. According to a study based on oral and cutaneous administration of oxybenzone to laboratory rats, followed by blood, urine, fecal matter, and tissue sample analyses, this product is transformed within the body into three distinct metabolites: 2,4-dihydroxybenzophenone (DHB), 2,2-dihydroxy-4-methoxybenzophenone (DHMB), and 2,3,4-trihydroxybenzophenone (THB).

Oxybenzone declared as a contact allergen.

Benzophenone-3 has been linked to allergic contact dermatitis and photocontact dermatitis. Indeed, products containing oxybenzone can cause redness, swelling, itching, and fluid-filled blisters. In severe cases, anaphylaxis can occur. In a study involving 82 patients suffering from photodermatitis, more than a quarter showed a photoallergic reaction to oxybenzone.

Oxybenzone considered as ecotoxic.

BP-3 also has an unfavorable environmental profile. It is considered an environmental contaminant and is suspected of being a threat to coral reefs, being linked to bleaching phenomena and massive coral mortality. Apparently, numerous cases of coral bleaching have been recorded following the presence of sunscreen residues in the sea. Due to these constraints, some states such as Hawaii and the Palau Islands have reacted and banned the use of sunscreens containing benzophenone-3. However, this ban is somewhat controversial and criticized by many scientific experts. The various studies were conducted with very high concentrations, higher than those found in the environment, or direct application, either on isolated coral samples.

Similarly, other factors must be considered: the actual amount of sunscreen applied, the vastness of the ocean, and marine currents. The most severe threats to the marine ecosystem are, for example, climate change with an increase in water temperature. Several researchers thus state that the damage caused by sunscreens to corals is negligible. The available studies on the impact of oxybenzone on coral decline are limited and non-repetitive. Benzophenone-3 would also harm the growth and ongoing photosynthetic processes of green algae, and its presence could also threaten the health of aquatic fauna.

Oxybenzone, an endocrine disruptor?

Recent studies have reported estrogen-like activity in vitro on cells and in vivo on rats/zebrafish of BP-3. Apparently, it would have an acute effect on the levels of endogenous reproductive hormones in humans and would interfere with the functioning of the endocrine system (hypothalamic-pituitary-gonadal axis), thus potentially affecting human health, after a topical application.

This potential biological effect was first published in a study by LICHTENSTEIGER W. & al., where they demonstrated a 23% increase in the size of the uterus in immature rats following oral administration of oxybenzone. Subsequent studies were conducted to determine the equivalent amount of BP-3 to be used topically in humans to achieve the cumulative amount of orally administered oxybenzone in immature rats and reproduce the observed systemic estrogenic effect.

However, while some studies have concluded that BP-3 has potential hormone-disrupting power, others have observed no biologically significant effect on hormone levels, indicating that the amount of BP-3 absorbed is not capable of disrupting the homeostasis of endogenous reproductive hormones in humans, even with the application of a formulation containing 10% oxybenzone.

Indeed, the minor differences observed in the levels of testosterone, estradiol, and inhibin B do not seem to be linked to exposure to benzophenone-3. Given such contradictory results, the current data are not sufficiently legitimate to extrapolate to humans, and oxybenzone requires further in-depth studies.

Note : A study revealed that plasma concentrations of BP-3, 24 and 96 hours after the first application of a sunscreen formula, were not significantly different, neither in men nor in women, indicating that there is no accumulation, even after several days of topical application.

Oxybenzone, an aggravating factor or a promoter of cancer development?

Recently, studies have reported the potentiating effects of exposure to BP-3 in the progression of cancer. A 2008 report revealed that exposing human lung cancer cells to non-toxic concentrations of oxybenzone could confer a behavioral change in the cells towards mesenchymal phenotypes (epithelial-mesenchymal transition). This is a process that facilitates the formation of metastases, or the ability of anoikis-resistant tumor cells to migrate and invade surrounding tissues to form secondary tumors.

Other studies have reportedly identified effects of BP-3 on mammary tumorigenesis in female mice. In other words, oxybenzone would cause an increased proliferation of tumor cells and a reduced apoptosis of tumor cells through alterations in the immune cell populations of the tumor microenvironment. In conclusion, BP-3 would have the ability to potentiate the "aggressive" behaviors of cancer cells. However, further research is necessary to confirm this effect of benzophenone-3 in humans.

What are the conclusions?

The CSSC has concluded that the use of oxybenzone as a UV filter at concentrations up to 6% in sunscreen products does not pose a health risk, except as a potential contact allergen. Further investigations are necessary to assess the effects of BP-3 exposure on human health and the environment, in order to have conclusive evidence.

What we do know is that benzophenone-3 provides good sun protection, and helps prevent skin cancers, skin lesions, as well as the risk of sunburns. However, in light of these results, which are somewhat inconclusive, we prefer to err on the side of caution and have decided to exclude it from the formulation of our sunscreens as a precautionary principle, until further studies provide more clarity.

Sources

  • LARKÖ O. & al. Percutaneous absorption of benzophenone-3, a common component of topical sunscreens. Clinical and Experimental Dermatology (2002).

  • WULF H. C. & al. Systemic absorption of the sunscreens benzophenone-3, octyl-methoxycinnamate, and 3-(4-methyl-benzylidene) camphor after whole-body topical application and reproductive hormone levels in humans. Journal of Investigative Dermatology (2004).

  • PUSCEDDU A. & al. Sunscreens cause coral bleaching by promoting viral infections. Environmental Health Perspectives (2008).

  • LIM H. W. & al. Safety of oxybenzone: Putting numbers into perspective. Archives of Dermatology (2011).

  • CHOI K. & al. Effects of benzophenone-3 exposure on endocrine disruption and reproduction of Japanese medaka (Oryzias latipes) — A two generation exposure study. Aquatic Toxicology (2014).

  • BJERREGAARD P. & al. Endocrine-disrupting effect of the ultraviolet filter benzophenone-3 in zebrafish, Danio rerio. Environmental Toxicology and Chemistry (2015).

  • CHANVORACHOTE P. & al. Benzophenone-3 increases metastasis potential in lung cancer cells via epithelial to mesenchymal transition. Cell Biology and Toxicology (2016).

  • LOYA Y. & al. Toxicopathological effects of the sunscreen UV filter, oxybenzone (benzophenone-3), on coral planulae and cultured primary cells and its environmental contamination in Hawaii and the U.S. Virgin Islands. Archives of Environmental Contamination and Toxicology (2016).

  • MESINKOVSKA N. A. & al. The banned sunscreen ingredients and their impact on human health: A systematic review. International Journal of Dermatology (2020).

  • SCHWARTZ R. C. & al. Benzophenone-3 promotion of mammary tumorigenesis is diet-dependent. Oncotarget (2020).

  • DAVIES I. A. & al. A critical review of organic ultraviolet filter exposure, hazard, and risk to corals. Environmental Toxicology and Chemistry (2021).

  • PAWLAK K. & al. Benzophenone-3, a chemical UV-filter in cosmetics- is it really safe for children and pregnant women? Advances in Dermatology and Allergology (2022).

  • ANDERSSON A.-N. & al. Benzophenone-3- Comprehensive review of the toxicological and human evidence with meta-analysis of human biomonitoring studies. Environment International (2023).

  • SCHNEIDER S. S. & al. Benzophenone-3 exposure alters composition of tumor infiltrating immune cells and increases lung seeding of 4T1 breast cancer cells. Advances in Cancer Biology (2023).

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