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Disadvantages of Organic UV Filters

Conference Paper · October 2014

DOI: 10.13140/2.1.1499.2327

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Jacek Arct Katarzyna Pytkowska

Dr Seidel foundation Warsaw Poland Maria Skłodowska-Curie Medical Academy in Warsaw
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Disadvantages of organic UV filters
Jacek Arct, Katarzyna Pytkowska
Academy of Cosmetics and Health Care, Warsaw

The harmful effect of UV radiation present in the sunlight is obvious for everybody (1). UVB radiation,
which permeates to the basal layer, is absorbed i.a. by the bases of the nucleic acids, which causes
mutations and carcinogenesis. UVA radiation, which permeates deeper, is less absorbed and acts
indirectly via sensitizers (2), (3). Both types of radiation may cause mutations and lead to premature
skin aging. Nowadays, filters are among the most popular cosmetic ingredients, and are added not
only to typical sun-protecting products, but also to many personal care, hygiene and colour cosmetics
(4). Whereas controversies related to mineral filters, including the nanomisation problem, have been
largely resolved (5), (6), (7), nevertheless, organic filters raise multiple considerations due to their
potential ability to penetrate the skin, capability to affect body hormone activity, and photochemical
reactions occurring in the treated skin (8), (9).
It should be emphasized that so far no undisputed adverse activity of sunscreens with organic filters
has been reported, and their regular application is the best method of protecting the skin against
threats posed by UV radiation (8). These cosmetics, as it seems, fail to protect the skin against the
most serious of skin cancers, the melanoma. Considering the unquestioned link between UV activity
and melanoma incidence, is still difficult to find an explanation for this phenomenon (10), (11).
According to one of the theories based on statistical data, an important factor in melanoma genesis
may be side-effects of filter activity or products of their photodegradation (12).
The list of sun filters used in the EU is limited to the products defined in the European Council
Directive, which is in force in Poland.
Due to popularity of sun filters, they pose a hazard to health both in a direct contact with the skin, and
when they are disposed of in the form of sewage, from which they are not removed completely, even
in the countries with a well-developed network of sewage treatment plants (13), (14), (15). It was
established that with big doses applied orally toxic symptoms occurred in laboratory animals which
had been fed with BP-3, 4-MBC and OMC (16), (17). The results are contradictory to those obtained
by other authors (3).
The majority of classic filters penetrate the skin, permeate it, reach the circulatory system and can
have a systemic action on the body (18). The skin treated with filters and subsequently exposed to UV
radiation revealed an exacerbated presence of ROS (19), which points both to the filters’ ability to
penetrate the outermost skin layers, and to the pro-radical effect of some filters. The presence of
filters in urine and milk of the individuals who were applying cosmetics with filters to their skin
confirms the hypothesis about the ability of filters to permeate the skin. The amounts detected in the
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urine and milk of those patients reached 2% of the applied dose (20), (21), (22), (23). The permeation
of filters into the skin was confirmed by Treffel’s studies, revealing that BP-3, Octisalate and OMC
penetrate the skin (24). Also the direct in vitro tests confirm the ability of certain filters, primarily BP-
3, 4-MBC and OMC, to penetrate the epidermis and permeate the skin (25), (21), (26), (13). A method
to reduce filter bioavailability is to encapsulate them in microparticles with low skin-penetration
properties. It is also a method to protect the skin against the products of photoreaction (12).
The second potential threat posed by organic UV filters is their ability to bind and activate estrogen
receptors. This refers both to filter’s activity after its absorption by the skin from a cosmetic product,
and also to environmental interactions (11), (4), (9), (27). It has been established that a number of
filters reveal estrogenic activity (28). These include Benzophenone 3 (BP-3), 3-Benzylidene Camphor
(3-BC), 3-(4-methylbenzylidene Camphor (4-MBC), 2-Ethylhexyl Methoxycinamate (OMC), Homosalate
(HMS), 2-Ethyhexyl-4-dimethylaminobenzoate (OD-PABA), 4-Aminobenzoic Acid (PABA). The impact of
these filters on estrogen receptors α and β (ERα i ERβ) has been tested in vitro (28), (5). The results
differed in filters’ ability to bind with particular receptor types (ERα and ERβ); however, in all cases an
agonistic effect of filters on ER as such was observed. In other studies, an antagonistic effect of the
majority of tested substances on human ERα has been revealed. These findings have been confirmed
by some authors, yet questioned by others (6), (28). For some of the tested filters agonistic activity on
estrogen receptors has been confirmed in vitro during studies conducted on rats (6), (7).
In the case of filters Benzophenone 3 (BP-3), 3-Benzylidene Camphor (3-BC), 3-(4-methylbenzylidene
Camphor (4-MBC), 2-Ethylhexyl Methoxycinamate (OMC), Homosalate (HMS), 2-Ethyhexyl-4-
dimethylaminobenzoate (OD-PABA), in vitro tests revealed a pronounced antagonistic activity against
androgen receptors. Similar findings were obtained in studies on the impact of these compounds on
progesterone receptors, with the exception being 2-ethyhexyl-4-dimethylaminobenzoate (OD-PABA)
(2). Three endocrine-active filters, 3-BC, 4-MBC and OMC, have been tested in vitro on rats. The
findings confirmed reproductive toxicity. In both sexes, changes in biochemical indexes of reproductive
organs were discovered, as well as a certain inhibition of procreative behaviour (3), (16), (29), (30).
The impact of sun filters on hypothalmic-pituitary-thyroid axis has also been tested. In vitro and in vivo
tests revealed that BR-3 acts agonistically on thyroid receptors, and that it inhibits gene expression in
thyroid (31). Also 4-MBC and OMC disturb thyroid hormone production. This activity can be attributed
to the impact of the filters on the enzyme systems which control hormone production and inhibit
iodine absorption (31). Undoubtedly, it is Benzophenone 3 (BP-3) that reveals the best-documented
estrogenic activity. At the same time, it is one of the most frequently used UV filters (present in about
96% of protective cosmetics in the USA) (32)). Pro-estrogen and anti-androgen activity of BP-3 has
been confirmed in vitro in cancer cells (33), (34), (35). At the same time, it should be emphasized that
in studies conducted on humans after BP-3 exposure no hormone imbalance has been observed (25).

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Exposure to filters is not exclusively connected with cosmetic use. They can come from other
consumer goods, such as cleaning products, clothes, etc., protected against UV radiation (36), (23).

One of the basic requirements concerning sun filters is photostability. In practice, when exposed to
radiation, the majority of used filters undergo changes and degradation (37), (38). One of the filters
that are most susceptible to the reactions of this kind is Butyl Methoxydibenzoylmethane (BMDBM,
avobenzone). It is one of the best UV-A filters, (39), (16), (29). Definite instablility when exposed to UV
is revealed by Octyl Methoxycinnamate, which transforms into significantly less active cis-isomer (38).
Instability is also revealed by Ethylhexyl Dimethyl PABA, which undergoes fragmentation (16), and by
Ethylhexyl Triazone (30), (40). Reactions generated by sunlight irradiation are generally very complex.
The already mentioned BMDBM, when exposed to UV, disintegrates after reaching the excited state. It
generates singlet oxygen, which reacts both with the initial BMDM and with other cosmetic
ingredients. As a result, a number of products are formed with the potential irritating and allergenic
properties (37). The situation is even more complex when BMDBM is used in a mixture with a popular
UV-B filter, Octyl Methoxycinnamate. This filter is unstable in the conditions of UV irradiation and
additionally it reacts with singlet oxygen generated by BMDBM, forming with it cycloaddition products
(De Mayo reaction), which on UV exposure, undergo defragmentation, generating further xenobiotics
with an irritant potential (41). Not all filters react in the same manner, leading to the reduction of
protective properties and forming potentially toxic products. In many cases, an additional filter
stabilizes the primary product, prolonging its action. An example of this is a wide-spectrum filter that
belongs to a new generation, Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine (BEMT, Bemotrizinol),
which exquisitely prolongs the action of both, BMDBM and Octyl Methoxycinnamate.

Also other filters reveal similar properties. Depending on the environment, other stabilizing
mechanisms are also possible (41), (37), (40). In such cases, the best method to optimize the effect is
to perform appropriate experiments, parallel to those described in the literature (38), (1), (40).

Other cosmetic ingredients also play an important role in filter stabilisation. Examples are Titanium
Oxide and Zinc Oxide (41), (42), the presence of polar emollients (31), (17), and anti-free radical
substances (32), (35). One of the methods to stabilise filters is to add them to cosmetics in the form of
cyclodextrin complexes. A stabilising action has been observed in the case of Ethylhexyldimethyl PABA
and Butylmethoxy Dibezoylmethane (33), (34), (25). Currently, on the market there are numerous
sunscreens which contain unstable filters. This can be attributed to the fact that so far no appropriate
legal regulations have been devised which would unambiguously address the stability of a given filter
after UV absorption (43).

3
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