Photochemistry and Photobiology, 2020, 96: 779–797

Invited Review
Materials Science Challenges in Skin UV Protection: A Review
Orielia Pria Egambaram1,2 , Sreejarani Kesavan Pillai*2 and Suprakas Sinha Ray1,2
1
Centre for Nanostructures and Advanced Materials, DSI/CSIR Nanotechnology Innovation Centre, Council for Scientific and
Industrial Research, Pretoria, South Africa
2
Department of Chemical Sciences, University of Johannesburg, Doornfontein, Johannesburg, South Africa
Received 7 July 2019, accepted 11 December 2019, DOI: 10.1111/php.13208

ABSTRACT degenerative changes, such as diverse types of skin cancer. As

our skin is the first line of defense of our immune system, in
UV radiation is one of the critical environmental stress fac- regard to overexposure to UVR, this may even lead to adverse
tors for human skin, which can trigger various problems effects on the immune system (1). The incidence rates for ker-
such as pruritus, burning, erythema, premature skin aging atinocyte (basal cell and squamous cell carcinoma) and mela-
and skin cancer. Hence, UV protection has become an indis- noma have been rapidly increasing over the past few decades. It
pensable daily routine and the use of topical sunscreen prod- has been found that solar UVR is the leading cause of this, lead-
ucts is rapidly increasing. However, there are emerging ing to 50–70% of all squamous cell carcinomas and 50–90% of
concerns over the efficiency and safety of existing chemical all basal cell carcinomas (2). Statistics provided by the World
and physical UV filters used in consumer products. Further- Health Organization (WHO) indicate that as of 2018 there was a
more, there is no universally approved method for assessing global incidence rate of 2–3 million keratinocyte skin cancers
sun protection efficiency regardless of the immediate end user and 132 000 melanoma skin cancers. The WHO has further sta-
need to develop safer sunscreen products that afford broad- ted that one in every three cancers, which are diagnosed, are
spectrum photoprotection. It is evident that the current some form of skin cancer (3). Furthermore, it is widely reported
organic and inorganic UV filters have significant unfavorable that lighter-skinned populations are more susceptible to develop-
impacts on human, environmental, and marine safety. There- ing nonmelanoma skin cancer due to increased exposure to UVB
fore, effective alternative UV filters should be established. radiation (4). The lower incident rate of skin cancers in popula-
This article comprehensively reviews the properties, safety, tions with darker skin is attributed to the presence of melanin,
health and ecological concerns of various UV filters including which provides the skin with natural UVR filtering and photo-
TiO2 and ZnO nanoparticles as well as the limitations of the protection (5). According to a study conducted by D. Fajuyigbe
testing protocols and guidelines provided by major regula- et al. (6), the occurrence of DNA photodamage, which leads to
tory bodies. The photoreactivity of UV filters used in sun- keratinocyte skin cancer, is reduced 10-fold in individuals with
screen remains a major challenge, and it is crucial to develop higher pigmented skin (West African SPT VI skin) when com-
new sunscreen ingredients, which not only protect the con- pared to light colour skin (SPT I and II skin). Recent statistics
sumer, but also the environment. obtained from the United States and South Africa have also
demonstrated the higher incidence of keratinocyte cancer in indi-
INTRODUCTION viduals with lighter skin compared with those with darker skin
(7). According to the Cancer Association of South Africa
As humans, we cannot deny the fact that sunlight is of the (CANSA), South Africa has the second highest skin cancer inci-
utmost importance for our existence. Quite simply put, without dence rate in the world, after Australia, with an increasing num-
sunlight, life on this planet would cease to exist. Sunlight con- ber of melanoma cases being reported over recent years. Despite
sists of a wide range of electromagnetic radiation including infra- the reduced vulnerability of some groups of the population, they
red, visible and ultraviolet light. Sunlight is the only natural are still prone to photodamage, which may present as wrinkles,
source of ultraviolet radiation (UVR) and cutaneous exposure to pigmentation and, in some cases, sunburn (7).
UVR is necessary for the endogenous production of vitamin D3, The Earth’s ozone layer is a layer above the earth containing
which also aids skeletal growth and development (1). high levels of ozone (O3) that can absorb ~99% of all harmful
However, research indicates that overexposure to UVR leads UVR from sunlight, which is known to be damaging to both
to more significant damage to skin rather than providing addi- plants and animals (5). Therefore, this layer is highly beneficial
tional benefits. The consequences of UVR overexposure on the to human life and the depletion or damage thereof will have sev-
skin may be classified into two different categories: acute and ere detrimental effects. Ozone is a natural gas and is present in
chronic. Chronic UVR overexposure leads to potential average amounts of 300–350 Dobson units (D.U.). With the
depletion of the ozone layer over time, more UVR can reach the
*Corresponding author email: [email protected] (Sreejarani Kesavan Pillai) earth’s surface thereby evoking damage that is more significant.
© 2019 American Society for Photobiology

779
780 Orielia Pria Egambaram et al.

It is estimated that a 10% depletion of the ozone layer may result of high energy and may be absorbed directly by the DNA bases,
in an increase in keratinocyte and melanoma cancers by 300 000 which will lead to the development of mutagenic lesions and
and 4500, respectively.(4) skin cancer (1,5).
Sunburn is identified as a common after effect of overexpo- Shorter wavelength UVC radiation is typically neglected as it
sure to sunlight. However, premature skin aging, skin cancer, only accounts for 5% of the overall electromagnetic spectrum
erythema and pruritus are some of the significant environmental with most of it attenuated by the ozone layer and atmospheric
stress agents for human skin, which are caused by UVR. These gases (10). UVC has a lower probability of penetrating the skin
environmental stress agents, which currently pose a threat, are when compared to UVA and UVB due to its complete absorp-
capable of affecting individuals of any age or race. Thus, photo- tion by skin chromophores. Skin chromophores such as DNA,
protection has become an increasingly important topic, which urocanic acid, amino acids and melanin can fully absorb UVC
has subsequently led to the widespread use of sunscreen agents. radiation, thereby performing the function of a UV filter (12).
However, the efficacy as well as safety of sunscreen agents, However, there have been a few reports on the possible carcino-
especially organic UV filters, has been recently brought into genic and mutagenic properties of this radiation. On the other
question. Specific allergic reactions or toxic degradation products hand, UVC radiation is known to exhibit germicidal activity,
may arise when sunlight transforms UV filters into reactive inter- which is beneficial to humans (13).
mediates. Such intermediates may even penetrate the skin caus- The intensity of radiation reaching the earth’s surface may be
ing further stress on the skin (8). In 2014, an article by Nash influenced by an array of factors including environmental pollu-
and Tanner (9) evaluated the photostability of sunscreen products tants, cloud cover, ozone levels, altitude, longitude and latitude,
and its subsequent impact on human health. The article critically and seasonal changes. The ozone layer plays a pivotal role in fil-
discussed the issue of photostability at length and highlighted tering the amount of UVR that ultimately reaches the earth’s sur-
that this issue has existed since the initial development of sun- face by means of photoabsorption (13). Man-made
shielding agents. Despite the prior occurrence of photo-unstable chlorofluorocarbons (CFCs), which are present in aerosols,
sun-shielding agents, the article highlighted the importance of refrigerators and air-conditioning units, are known to deplete the
understanding the effects of different combinations of UV filters ozone layer (1,10,13). Depletion of the ozone layer poses grave
so as not to create a worse effect. consequences for human life as less and less UVR will be fil-
In this review, we have carried out an extensive literature sur- tered. However, according to the 2015 United Nations Environ-
vey with respect to the emerging concerns over the efficiency ment Programme report (5), the stratospheric ozone layer has
and safety of existing chemical and physical UV filters, and recovered over the last few years with a forecast of a slow return
nanomaterials used in current topical sunscreen products. This to pre-1980 levels in the coming decades. The stratospheric
article comprehensively reviews the properties, safety, and health ozone layer efficiently screens nearly all UVC radiation before
and environmental concerns of various UV filters as well as the reaching the earth’s surface. All UVA radiation passes through,
limitations of the testing protocols and guidelines provided by while 90% of UVB and 100% of UVC are filtered, as reported
major regulatory bodies, which make it unique from previously by Wang et al. (14) Although incident UV radiation is no longer
published review articles on this topic. increasing due to depletion, environmental factors such as ice,
snow and cloud cover, and precipitation levels as well as the
effects of climate change ultimately modify the overall exposure
TYPES OF RADIATION AND THEIR EFFECTS
of organisms to UVB, UVA and visible light radiation (5).
ON SKIN
Quite possibly the most alarming development to date with
While we are exposed to a wide range of radiation, both visible regard to UVR and skin damage is the fact that visible and infra-
and invisible, it is our excessive exposure to UVR that is most red radiation may also be harmful to human skin. Visible light,
detrimental to human skin. Thus, UVR has the most considerable which makes up approximately half of the electromagnetic spec-
medical importance, particularly in regard to sun-protective trum, can penetrate deep into the biologic tissues and up to 20%
agents. UVR may be initially split into UVA (315–400 nm), of this radiation may even reach the level of the hypodermis. A
UVB (280–315 nm) and UVC (200–280 nm) (Fig. 1). Long- study has been conducted to determine the relative contribution
wave UVA [UVA II (315–340 nm) and UVA I (340–400 nm)] from different kinds of radiation made toward the formation of
is known to penetrate deeper into the skin and may reach the ROS and thereby quantify, which was the most harmful. The
level of the dermis. It is believed that the damage caused by results indicated that when the skin was irradiated with visible
UVA is less severe when compared to that by UVB. However, light, an estimated 50% ROS generation occurred, while UVB
recent studies have proven that UVA generates reactive oxygen and UVA exhibited 4% and 46% ROS generation, respectively.
and nitrogen species (ROS and RNS), which may lead to Furthermore, it was found that visible light may even affect the
changes in the DNA, lipids and proteins present in the body. structure of DNA via the formation of oxidized DNA bases.
Furthermore, oxidative damage may lead to premature skin aging Even though visible light can change the structure of DNA, it
and excessive skin wrinkling (10,11). has been reported that only ~10% of DNA damage may be
UVB radiation accounts for a smaller portion of the electro- caused by exposure to solar radiation (10,15).
magnetic spectrum when compared to UVA, but it is more likely Infrared (IR) radiation with the lowest energy can be divided
to cause skin redness due to its significant absorption by skin into three types: IRA (700–1400 nm), IRB (1400–3000 nm) and
chromophores, such as DNA (12). When compared to UVA, it IRC (3000 nm–1 mm). While IRC and IRB cannot penetrate
has lower skin penetration capabilities, but it can penetrate down deeply into the skin, IRA can trigger the formation of ROS
to the epidermal layer of the skin. At this level, it can generate within the skin. IRA may also lead to an unbalanced gene
ROS and RNS, which ultimately lead to an inflammatory expression of matrix metalloproteinase (MMP), which is the
response, sunburn and premature skin aging. UVB photons are main group of enzymes responsible for collagen and other
 Photochemistry and Photobiology, 2020, 96 781

Figure 1. The electromagnetic spectrum including UVA, UVB and UVC.

protein degradation processes occurring in the extracellular increased. Sunscreen products usually contain ingredients that
matrix (ECM) (10). These effects may ultimately influence the can effectively absorb or scatter UVR. However, the UV filters
integrity of the mitochondria present within the cells. IRA makes included in sunscreens need to be nonirritant, nonsensitizing and
up ~30% of all infrared radiation; however, only 65% and 10% nonphototoxic and should remain stable on human skin when
of this radiation reaches the dermis and hypodermis, respectively. exposed to sunlight (11).
Ultimately, the formation of wrinkles due to photoaging results UV filters are constituents present in topical formulations that
from stimulated collagen degradation and reduced collagen have the capacity to interact with UVR via three fundamental
renewal, which is caused by an increase in MMP and a decrease mechanisms: reflection, scattering and absorption (Fig. 3).
in COLIA1 expression (16). IR radiation is typically poorly UV filters are generally classified into inorganic or organic fil-
absorbed by skin chromophores, such as melanin, and thus, it ters, according to their physicochemical properties. Inorganic fil-
has been proposed that the mode of action for the damage occurs ters can reflect or scatter incident UVR via an optical
via the mitochondria and cytochrome C oxidase (10). The skin mechanism. The main feature of an inorganic filter is its struc-
penetration levels of various types of solar radiation are depicted tural stability to maintain photoprotection even after long periods
in Fig. 2. of UVR exposure, whereas organic filters obstruct the UVR via
absorption (17,18). The classification of the topical sunscreen
ingredients currently available is given in Fig. 4. As the focus of
UV FILTERS
this review is mostly on the UV filters used in topical sunscreen
Given the increasing dangers associated with exposure to UVR, formulations, systemic sunscreen agents have not been compre-
the use of sunscreen agents in various topical formulations has hensively reviewed.

Figure 2. Skin penetration levels of ultraviolet (UVA and UVB) and infrared (IRA, IRB and IRC) radiation (adapted from Ref (10)).
782 Orielia Pria Egambaram et al.

Figure 3. Mode of action of (a) organic and (b) inorganic UV filters on the epidermis.

Figure 4. Classification of the various topical sunscreen agents currently available.

A list of approved UV filters and their maximum allowed

concentrations in commercial cosmetic products has been set by ORGANIC UV FILTERS
the EU. Table 1 shows 28 EU approved UV filters and their Many sunscreens contain synthetic organic chemicals known as UV
maximum allowed concentration. filters. Organic UV filters are often termed chemical UV filters as
 Photochemistry and Photobiology, 2020, 96 783

Table 1. List of organic UV filters permitted in cosmetic products according to the current EU legislation, EC 2009.
Maximum allowed
Chemical name/Common name INCI concentration (%)

N,N,N-Trimethyl-4-(2-oxoborn-3-ylidenemethyl) anilinium methyl sulfate Camphor benzalkonium methosulfate 6%

Benzoic acid, 2-hydroxy-, 3,3,5-trimethylcyclohexyl ester/homosalate Homosalate 10%
2-Hydroxy-4-methoxybenzophenone/oxybenzone Benzophenone-3 6%
2-Phenylbenzimidazole-5-sulfonic acid and its potassium, sodium and Phenylbenzimidazole sulfonic acid 8% (as acid)
triethanolamine salts/ensulizole
3,3’-(1,4-Phenylenedimethylene)bis(7,7-dimethyl-2-oxobicyclo-[2.2.1] Terephthalylidene dicamphor sulfonic acid 10% (as acid)
hept-1-ylmethanesulfonic acid) and its salts/ecamsule
1-(4-tert-Butylphenyl)-3-(4-methoxyphenyl) propane-1,3-dione/ Butyl methoxydibenzoylmethane 5%
avobenzone
Alpha-(2-Oxoborn-3-ylidene)toluene-4 sulfonic acid and its salts Benzylidene camphor sulfonic acid 6% (as acid)
2-Cyano-3,3-diphenyl acrylic acid 2-ethylhexyl ester/octocrilene Octocrylene 10% (as acid)
Polymer of N-{(2 and 4)-[(2-oxoborn-3-ylidene)methyl]benzyl} Polyacrylamidomethyl benzylidene 6%
acrylamide camphor
2-Ethylhexyl 4-methoxycinnamate/octinoxate Ethylhexyl methoxycinnamate 10%
Ethoxylated ethyl-4-aminobenzoate PEG-25 PABA 10%
Isopentyl-4-methoxycinnamate/amiloxate Isoamyl p-methoxycinnamate 10%
2,4,6-Trianilino-(p-carbo-2’-ethylhexyl-1’-oxy)-1,3,5-triazine Ethylhexyl triazone 5%
Phenol, 2-(2H-Benzotriazol-2-yl)-4-methyl-6-(2-methyl-3-(1,3,3,3- Drometrizole trisiloxane 15%
tetramethyl-1-(trimethylsilyl)oxy)-disiloxanyl)propyl
Benzoic acid, 4,4-{[6-[[[(1,1-dimethylethyl)amino]carbonyl]phenyl] Diethylhexyl butamido triazone 10%
amino]-1,3-5-triazine-2,4-diyl]diimino}bis-,bis(2-ethylhexyl)ester/
iscotrizinol
3-(4’-Methylbenzylidene)-dl-camphor/enzacamene 4-Methylbenzylidene camphor 4%
2 -Ethylhexyl salicylate/octisalate) Ethylhexyl salicylate 5%
2-Ethylhexyl 4-(dimethylamino)benzoate/padimate O Ethylhexyl dimethyl PABA 8%
2-Hydroxy-4-methoxybenzophenone-5-sulfonic acid (benzophenone-5) Benzophenone-4; benzophenone-5 5% (as acid)
and its sodium salt/sulisobenzone
2,2’-Methylene bis(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl) Methylene bis-benzotriazolyl 10%
phenol)/bisoctrizole tetramethylbutylphenol
Sodium salt of 2,2’-bis(1,4-phenylene)-1H-benzimidazole-4,6-disulfonic Disodium phenyl dibenzimidazole 10% (as acid)
acid/bisdisulizole disodium tetrasulfonate
2,2’-(6-(4-Methoxyphenyl)-1,3,5-triazine-2,4-diyl)bis(5-((2-ethylhexyl) Bis-ethylhexyloxyphenol methoxyphenyl 10%
oxy)phenol)/bemotrizinol triazine
Dimethicodiethylbenzalmalonate Polysilicone-15 10%
Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexylester Diethylamino hydroxybenzoyl hexyl 10%
benzoate
2,4,6-Tris(1,1’-biphenyl)-4-yl-1,3,5-triazine including its nanomaterial Tris-biphenyl triazine/tris-biphenyl triazine 10%
(nano)
3,3’-(1,4-Phenylene)bis(5,6-diphenyl-1,2,4-triazine) Phenylene bis-diphenyltriazine -
Titanium dioxide Titanium dioxide 25%*
Titanium dioxide (nano)
Zinc oxide Zinc oxide 25%*
Zinc oxide (nano)

*In case of the combined use of zinc oxide and zinc oxide (nano), the sum shall not exceed 25%.

their method of action is to absorb UVR to prevent it from reaching process of both organic filters. Sayre et al. (22) conducted a study
the skin, which involves a series of chemical changes in these mole- using thin films of sunscreen product containing avobenzone/oxy-
cules. These filters are typically aromatic compounds containing a benzone/OMC in a molar ratio of 1:1:2. The study revealed that
carbonyl group, such as salicylates, cinnamates and benzophenones after 90 min of UVA exposure, the components did not degrade at
(Table 1) (19). An example of a widely used organic UV filter is octyl the same rate: 20% of avobenzone and 40% of OMC remained,
methoxycinnamate (OMC). These organic filters have three different while the oxybenzone concentration was unaffected. Overall, the
ways in which they react when they encounter UVR: releasing inci- results indicated that the photodegradation of OMC increased sig-
dent energy as heat, undergoing changes in their molecular conforma- nificantly due to the decomposition products (free radical frag-
tion and emitting radiation at a higher wavelength. Combining ments) of avobenzone and its lack of photostability under UVA
several organic UV filters is common practice to achieve broad-spec- radiation. Another study by Freitas et al. (23) on the photostability
trum UV protection (UVA and UVB) and the required sun protection of five commonly used UV filters in three different combinations
factor (SPF) value for a sunscreen formulation. However, it has been also concluded that the formulations containing avobenzone dis-
noted that the photostability of organic UV filters may decrease when played a higher rate of photodegradation, which was only decreased
combining several organic filters (20). when antioxidants were included in the formulation (23).
Studies have shown that certain combinations of organic UV fil-
ters become undesirable as they are known to increase the competi-
tive photodegradation process. Kim et al. (21) observed that a
SAFETY OF ORGANIC UV FILTERS
formulation containing OMC and avobenzone exhibits elevated When organic UV filters encounter UVR, the filters may release
levels of photodegradation attributed to the competitive degradation ROS/free radicals, which may cause damage to collagen, elastin
784 Orielia Pria Egambaram et al.

and DNA (24). Furthermore, it has been reported that there are understand the mechanisms of action and role of OMC in endo-
other crucial issues associated with the use of organic UV filters: crine, reproductive, cardiovascular and neurodegenerative disor-
absorption through the skin leading to systemic exposure to the ders in humans (32).
filters, which may act as endocrine disruptors, and degradation Although it is expected that these filters should be stable,
by UVR exposure, which renders them photo-unstable and especially under UVR, due to their close contact with human
unable to protect from UVR (25). skin, this is, unfortunately, not the case for organic UV filters.
Organic UV filters have been reported to exhibit adverse cuta- Research has shown that upon the absorption of UVR, organic
neous adsorption, which can be categorized into three stages: penetra- UV filters change on a molecular level, which leads to the for-
tion, permeation and resorption. During penetration, the filter enters mation of chemically reactive species. Being photo-unstable
the stratum corneum, the uppermost layer of skin. After that, it means the filters are unable to resist the permanent effects of
undergoes permeation, moving from one layer of skin to the other. UVR in terms of their structure and function. The reactive spe-
Finally, resorption takes place, wherein the filter is taken up into the cies generated ultimately allow photo-oxidation to occur, which
vascular system via either blood or lymph vessels (25). A study con- leads to the generation of free radicals. The lack of photostability
ducted by Toutiou and Godin in 2008 revealed that benzophenone- is also related to the decreased efficiency of the UV filter as a
3 (BP-3) and octyl salicylate (OS) can potentially penetrate the epi- sun-screening ingredient because they undergo changes that
dermis and be absorbed into deeper layers (26). cause a reduced ability to absorb UVR, which decreases the pho-
Humans are exposed to organic UV filters via topical cosmetic toprotection provided by the filter (25).
applications, which allow for the filter to penetrate the skin For example, OMC, a commonly used organic UV filter, is
directly without undergoing metabolism by the liver (25). Possible known to undergo isomerization, degradation and dimerization
estrogenic effects are also associated with the use of organic UV via direct (in the presence of natural sunlight) and indirect (in
filters, which are attributed to the endocrine disrupting potential presence of dissolved organic matter) photolysis in nonpolar as
displayed by organic filters. It was only in 2001 that researchers well as aqueous solutions despite being designed with photosta-
discovered the adverse effects of organic UV filters on the endo- bility, which results in the formation of dimers and cyclodimer
crine gland, and since then, several studies have been conducted isomers (41). In water bodies such as swimming pools, organic
to investigate the probable impairment of the endocrine system UV filters can be further degraded through exposure to sunlight
caused by these filters (25). Endocrine disruptors are compounds and their reaction with disinfectant products, such as chlorine
that are known to cause severe effects on a developmental, repro- (42). Organic filters such as ethylhexyl dimethyl PABA have
ductive and neurological level caused by the disruption of the been reported to rapidly react with free chlorine leading to
body’s’ endocrine system (27). For example, a study by Durrer mono- and dichlorinated by-products, which may affect human
et al. (28) has shown that prolonged exposure to 4-methylbenzyli- health causing respiratory and bladder diseases (41).
dene camphor (4-MBC) and 3-benzylidene camphor (3-BC) led to Octocrylene (OC) may be classified as one of the most pho-
a delay in the onset of male puberty as well as a reduction in the toallergic filters. Similar to other organic UV filters, OC has a
prostrate weight when Long Evans rats were orally exposed to relatively low molecular weight and lipophilic character, which
these filters (28). 3-BC and 4-MBC were also used in several allows it to permit through the intercellular spaces between the
developmental studies wherein it was found that the filters affect stratum corneum (43). A report by Hanson et al. (44) in 2006
proteins, insulin-like growth factor I (IGF-1), nuclear receptor revealed that OC was able to produce ROS in living human epi-
corepressor (N-Cor) and steroid receptor coactivator 1 (SRC-1) in dermis cell layers following UVR exposure. Given its structure,
the uterus and prostrate of adult oophorectomized rats (29). Many it was found using two-photon fluorescence microscopy that OC
benzophenone-based UV filters have been identified as endocrine is also able to generate ROS in the cytoplasm of human epider-
disruptors and are involved in the disruption of the hypothalamic– mis nucleated keratinocytes after exposure to UVR (43).
pituitary–gonadal system (30). Similarly, it is shown that OMC BP-3 is known to exhibit a vast array of toxicological effects
exerts estrogenic, antiprogestenic and antithyroid activity in ani- and has the highest incidence rate of photoallergic contact der-
mals and humans whereas the antiandrogenic activity is reported matitis. Studies involving the topical application of sunscreen on
only in animals (31,32). Based on the studies carried out in ani- human volunteers conducted from 1997 and 2002 have shown
mals (both in vitro and in vivo), it is understood that OMC may that 1–3% of the total amount of BP-3 applied is present in the
interfere with the synthesis, metabolism, distribution and action of urine samples collected. They also conducted a whole-body topi-
thyroid hormones by multiple targets and interferes with the cal application study, which showed BP-3 was detected in
hypothalamus–pituitary–thyroid axis at different levels (33,34). It human blood plasma 4 days after the study. The amount of sun-
was also established that OMC exerts estrogenic activity by a screen applied was in accordance with the maximum allowed
mechanism different from the classic estrogen receptor mechanism concentration as per European Union standards. There were also
(35,36). The androgenic and progestenic activities of OMC trace amounts of BP-3 found in breastmilk following topical
showed an antagonist action (35–37). Moreover, increased expo- application (43). Other studies have revealed the reproductive
sure to OMC is also shown to increase infertility, or changes of toxicity of BP-3, wherein it has been observed to induce unex-
reproductive hormone levels, leading to a decrease of the repro- plainable mortality in lactating mothers, as seen in a mice. In
ductive success in animals (38). other mammals, BP-3 exhibits endocrine disrupting functions,
Most of the studies on effect of OMC in humans were done mainly by controlling estrogen receptor signaling pathways,
in vitro and the results prove estrogenic, antiprogestenic and reducing reproductive fitness and inducing reproductive patholo-
antithyroid activities (39,40). However, the androgenic activity gies. In fish, it was found that chronic exposure to BP-3 resulted
was not observed in human cells. The reported results are based in the reduced production of eggs and induced vitellogenin pro-
on exposure to a single concentration and for a short interval of tein in males, which prompted researchers to question the proba-
time which indicates the need for more comprehensive studies to bility of “gender shifts” due to BP-3 exposure (45).
 Photochemistry and Photobiology, 2020, 96 785

Camphor derivatives, such as 4-methyl benzylidene (4-MBC) become transparent, while still absorbing UVR, resulting in a
camphor and 3-benzylidene (3-BC), are also widely used as substantial aesthetic enhancement. However, small-sized particles
organic UV filters as they exhibit UVR protective capabilities. tend to have decreased efficacy and are often more photoreactive
A study conducted using a porcine skin model revealed that 4- (46). Moreover, several studies indicate that there are certain
MBC can bind competitively to estrogen receptors in rats, instances whereby ZnO and TiO2 nanoparticles have been able
which then leads to the transactivation of these receptors (31). to penetrate the skin and cause toxic effects.
A further study, which was also carried out in a rat model in A particular study of interest was conducted in 2004 by
2005, revealed that ingestion of 4-MBC may result in a change Menzel et al. (47). A pig skin model was used to test the pen-
in the expression of estrogen-regulated genes in the uterus. etration ability of TiO2 nanoparticles (45–105 nm long and 17–
Both 4-MBC and 3-BC can elicit estrogenic activity on human 35 nm wide) from four different sunscreens, which were avail-
tumor mammary cells in vitro, which lead to their proliferation. able in the market. The results showed that some TiO2
On a global scale, it was found that exposure to 0.7 mg kg 1 nanoparticles were able to penetrate the intracellular spaces of
of 4-MBC during an early developmental stage can lead to the stratum corneum and potentially reach living tissue. How-
changes in the expression of estrogen receptor nuclear receptor ever, a major downfall was that the methods used to test the
coregulators and estrogen target genes within the rat uterus toxicity, as well as the models themselves, vary between each
(43). The adverse effects of other organic UV filters have been of the studies conducted, thus making the studies somewhat
reported. Octyl-triazone has been reported to act as a potent controversial (25). Considering all these studies, it appears that
sensitizer, which can cause allergic contact dermatitis in chil- ZnO and TiO2 nanoparticles can evoke certain deleterious dam-
dren and photoallergic contact dermatitis in adults. Salicylate age in living skin cells.
compounds are shown to penetrate the human epidermis by
tape stripping experiments and they have also been noted to
TiO2
enhance the in vivo proliferation of human tumor mammary
cells (43). TiO2 is a metal oxide with a high refractive index, which is
A combination of organic UV filters has been used in an available in three different crystalline forms: rutile, anatase and
attempt to decrease the adverse effects experienced. However, brookite (43). However, for application in sunscreen, it has been
not all combinations are suitable, and some may even evoke a found that rutile and anatase are relevant due to their low band
higher degree of damage than the individual components alone. gap energy of 3.0 and 3.2 eV, respectively. An average refractive
Most studies have confirmed the potential of organic UV filters index of 4.0 has been reported for rutile films and 3.6 for anatase
to penetrate the skin and cause adverse effects due to the forma- films (48). One of the substantial differences between the rutile
tion of ROS. The evidence described beforehand supports and anatase is the fact that anatase is more photoactive (13).
that the use of organic UV filters in sunscreen formulations can As with all inorganic UV filters, TiO2 acts by reflecting or
cause adverse effects on human health. It is due to such findings scattering UVR. For an inorganic filter in sunscreens, it has been
that the use of organic filters has been questioned extensively, declared that the safety threshold is up to 25% of the concentra-
which has resulted in the increased preference for the use of tion of the formulation by weight. As a result of the catalytic
inorganic UV filters in sunscreens. activity that the metal oxide has, it has been noted that it is cap-
able of forming superoxide and hydroxyl radicals upon the irra-
INORGANIC UV FILTERS diation with UVR. These ROS are known to cause DNA damage
and potentially cell death (13).
Inorganic UV filters are physical filters because their mode of
action refers to the scattering and reflection of light, which is a
physical phenomenon. Examples of inorganic UV filters include ZnO
ZnO, TiO2, kaolin and ichthammol, where ZnO and TiO2 are Similar to TiO2, the mode of action of ZnO is to either scatter or
the most commonly used. These inorganic filters have several reflect UVR. This particular property allows for an increase in
advantages over their organic counterparts, such as providing the optical pathway of the photons, which enhances the SPF and
UV protection from both UVA and UVB (broad-spectrum cov- thus increases the efficacy of the product. ZnO typically protects
erage). They are also photostable, while organic filters are not within the UVA region, whereas TiO2 covers UVB and part of
always photostable and may lead to allergic skin reactions (13). the UVA region (13). Sun and Kwok (49) reported refractive
There has been an increase in the use of inorganic UV filters index values between 2.3 and 2.4, and hence, comparable with
rather than organic UV filters specifically in products for chil- TiO2, the whitening effect of ZnO is lower. ZnO also has a rela-
dren and people with sensitive skin because they have a lower tively small band gap (3.37 eV), making it favorable for use in
potential for producing irritant reactions (20). Various inorganic sunscreen formulations.
filters such as ZnO and TiO2 have been used in sunscreens for
decades because they are active broad-spectrum sunscreen
agents. ZnO typically provides protection within the UVA Photochemistry and photophysics of ZnO and TiO2
range, whereas TiO2 covers the UVB region and part of the When semiconductors are exposed to UVR with an energy value
UVA range (13). greater than their band gap, a photocatalytic reaction occurs at an
Although the larger particles of TiO2 and ZnO adequately orbital level. The absorption of light excites a valence electron
reflect UVR in specific ranges, their higher refractive index and (e ) from the valence band of the material (lower energy level)
larger size make the formulation opaque and leave white residues to the conduction band, which is at a higher energy level. This
on the skin. If the particles are prepared on the nanoscale, they excitation results in a hole (h+) being formed in the valence
will be too small to scatter or reflect visible light and thus band, which represents a highly localized electron vacancy (50).
786 Orielia Pria Egambaram et al.

When TiO2 absorbs UVR, an electron from the O-2p orbi-

tal is excited to the conduction band, which is made up by
the Ti-3d orbital, thereby forming a hole in the valence band.
[15] A superoxide radical anion (O2
) is formed when pread-
sorbed molecular oxygen takes up the free electrons. The
holes produced then oxidize the surface hydroxyl groups and
generate hydroxyl radicals (OH
), which then initiate the oxi-
dation process. If the medium is acidic, the superoxide anion
will then be protonated to yield the hydroperoxyl radical
(HO2
), which ultimately produces hydrogen peroxide (H2O2)
(20).
After the electron and hole have been separated, there are two
charge carriers that move to the surface and then initiate redox
chemistry with available donor and acceptor molecules. A series
of recombination events may then yield emissions, which are
radiative or nonradiative, and the carriers may then be trapped
into lattice sites (20). Scheme 1 depicts a simplified version of
the events that occur after irradiation with UVR.
ZnO is direct band gap semiconductor, which absorbs in the
low energy UVA region, unlike the direct-forbidden band gap
TiO2 semiconductor. ZnO has a band gap of ~3.2 eV, while
TiO2 has a band gap of ~3.1 eV. Despite the proximity between
their band gaps, TiO2 can absorb more UVB radiation, while
ZnO absorbs more UVA radiation, which is due to the densely
packed electron states of TiO2 that allow for many absorption Scheme 1. The photochemical and photo-physical events that occur on
possibilities (50). The attenuation of UVR by these particles is metal oxide semiconductors after UV irradiation. [Color figure can be
also partly due to their scattering and reflecting mechanisms. viewed at wileyonlinelibrary.com]
Nanosized particles exhibit an enhancement in their light absorp-
tion due to the enhanced number of surface atoms. In direct-for-
bidden gap semiconductors, such as TiO2, direct electrons found on the skin barrier or in the tissues reached by systemic
transmissions are determined by the symmetry of the crystal circulation.
structure. Therefore, when absorption occurs at the crystal sur- In 1997, Dunford et al. (51) showed that when plasmid DNA
face, the intake amount is enhanced (50). was exposed to simulated sunlight containing UVA and UVB
rays in the presence of TiO2 particles, the resulting hydroxyl rad-
icals accelerated the cleavage of the DNA strands. As a result of
SAFETY OF INORGANIC UV FILTERS this finding, it was then assumed that should TiO2 enter viable
cells it would pose a severe health hazard. This study was car-
Skin penetration ried out in vitro on human fibroblasts. However, it was not stated
Research indicates that there are several downfalls to the use of whether the study used nanosized particles.
inorganic UV filters. In particular, the fact that such agents may Penetration of TiO2 microparticles into the horny layer of skin
be absorbed by the skin and are quite photoreactive may lead to was studied by Lademann et al. in 1999 (52). This study focused
the formation of ROS on the skin, which is harmful. on the possibility that TiO2 may be localized in the orifices of
Numerous studies have been conducted to determine the effi- hair follicles, which reach down into the dermis. A tape stripping
cacy of current sunscreen formulations, particularly investigating method was used to remove layers of skin following the deposi-
their cytotoxicity and phototoxicity. The information obtained tion of sunscreen containing TiO2 on the specified area. Biopsies
from certain cell experiments indicates that ZnO and TiO2 may were also carried out to determine whether there had been deeper
induce free radical formation when irradiated with UVR, which penetration. The results revealed that no TiO2 was found in the
may lead to cell damage and mutagenic effects. These effects deeper layers of the stratum corneum. It was also found that as
are, however, only possible if the nanoparticles penetrate the s- the depth of the stratum corneum increased, the concentration of
tratum corneum and reach viable cells. To date, the weight of TiO2 decreased. Furthermore, there was no penetration of TiO2
the information available indicates that these nanoparticles into viable cells. However, this study did not discuss whether it
remain on the surface of the skin and are not able to penetrate was possible for TiO2 to move out of the follicles and move into
and reach viable cells. Various reviews have been published over viable tissues.
the years giving an indication of the safety of inorganic UV fil- Merely two years later, the group published an article outlin-
ters. These reviews all tend to follow the same path and con- ing the follicular penetration of substances applied topically. This
clude that the nanoparticles are safe and are preferred over study focused solely on TiO2 microparticles, which revealed that
organic UV filters (19,43). there were trace amounts of TiO2 located in the deeper parts of
However, given the structure of nanoparticles, they can exhi- the stratum corneum in the follicle orifices. The surrounding
bit a greater surface area and are thus thought to be more areas were found to be free of TiO2. TiO2 penetrated the acroin-
likely to produce ROS in comparison with their bulk materials. fundibulum of the follicles, but had not reached the layer of
The toxicity of nanoparticles may be due to cells, which are viable cells. Furthermore, it was noted that TiO2 was not found
 Photochemistry and Photobiology, 2020, 96 787

consistently throughout the hair follicles, but rather as 1 in every management and wastewater treatment. The effects of the photo-
10 follicles (53). catalytic activity are usually characterized by the production of
To study the possible penetration of ZnO nanoparticles in various radical species, such as hydroxyl radicals, superoxide
human skin in vitro and in vivo, Zvyagin et al. (54) focused on anion radicals and, in some instances, the production of a singlet
the use of imaging techniques. These imaging techniques oxygen anions (50).
allowed the visualization of the distribution of ZnO nanoparticles It has been observed that the anatase form of TiO2 exhibits
within the skins’ substructures. This study used a commercial the highest photoreactivity between the two forms. Uchino et al.
sunscreen product wherein the ZnO nanoparticles had a mean (56) irradiated anatase and rutile TiO2 with UVR and observed
size of 26 nm. The overall results showed that the ZnO nanopar- the higher formation of OH radicals with the anatase form of
ticles remained on the stratum corneum and were collected TiO2. Furthermore, the anatase form exhibited higher levels of
within the folds of skin or hair follicles. There was no penetra- cytotoxicity toward Chinese hamster ovary cells (50,57). Similar
tion of ZnO into viable skin cells. These results correlated well results were also observed by Sayes et al. (58) in 2006 when
with the results obtained by Cross et al. (46), which revealed that they evaluated the effect of nanoscale TiO2 on its cytotoxic and
ZnO particles were located on the outer surface of the stratum genotoxic effects. The photoreactivity of 10-nm spherical TiO2
corneum with no evidence of penetration to the lower stratum was measured by observing the photodegradation of Congo red
corneum layers. dye under UVR at a wavelength of 365 nm.
A review article by Nohynek et al. (55) provides a holistic In 2006, Hidaka et al. (59) conducted a study on the damage
view with regard to the possible risks of nanotechnology within caused to DNA as a result of UVR exposure on TiO2 and ZnO,
cosmetics. One of the main concerns, as described previously, is wherein it was found that supercoiled DNA contained an
whether the nanomaterials are absorbed and if absorbed, whether increased number of nicks. These plasmids then formed relaxed
they are they toxic. The article reviewed at length various toxicity and linear DNA due to hydroxyl radicals, which were generated
tests and found that as a result of in vivo testing, TiO2 and ZnO following irradiation of ZnO and TiO2. This mechanism revealed
nanoparticles were mostly nontoxic. There were certain in vitro that the hydroxyl radicals attack vital components of DNA,
studies reporting that there was a certain uptake of nanoparticles, which ultimately leads to the rapid degeneration of the DNA
but it was suggested that this is may be secondary to the phago- strand.
cytosis of cells, which had been exposed to a significant concen- The contribution from the photoreactivity of ZnO and TiO2
tration of the nanoparticles. It was found that nanoparticles are toward the genotoxicity of these particles is still not fully under-
most effective as UV filters when they are between 60 and stood. However, several reports indicate strong correlations
120 nm. Typically, TiO2 nanoparticles currently contained within between them. Hirakawa et al. (60) irradiated anatase and rutile
sunscreen formulations have an average size of 14 nm. It must be TiO2 nanoparticles within the range of 50–300 nm to understand
noted that dermal penetration varies significantly between the var- the mechanism of DNA damage. This study revealed that most
ious test subjects with pig and rat skin being 4 and 9 times more DNA damage mediated by anatase TiO2 at a concentration of 4–
permeable than human skin, respectively. The authors further 16 µg/mL was revoked due to the formation of hydrogen perox-
expressed that the toxicity of these nanoparticles should be based ide rather than the formation of OH radicals.
on their in vivo toxicity rather than in vitro assays. However, little Reports have mentioned that ZnO, although less photocat-
evidence exists depicting that compromised skin may be more alytic than TiO2, exhibits lower levels of stability during UV
susceptible to the penetration of nanoparticles. irradiation. This finding was confirmed by Mahalakshmi et al.
ZnO was first approved by the FDA in 1999 for SPFs. How- (61) who investigated the photocatalytic activity of Degussa P-25
ever, in 2003 the Scientific Committee reviewed the use of ZnO (commercial TiO2) and ZnO particles by observing the pho-
in cosmetic products and nonfood products intended for cus- todegradation of carbofuran. They believed that the increased
tomers (SCCNNFP) and concluded that there was a lack of reli- surface activity of TiO2 was responsible for the increased levels
able data on the percutaneous absorption of micronized ZnO and of photocatalytic activity observed.
that the possibility of inhalation of the particles had not yet been There are two main methods employed to prevent this photo-
considered. To date, many investigations have been carried out catalytic activity. The first method is to encapsulate the synthe-
to address these issues. A study from 2015 found that neither sized nanoparticles into a chemically stable shell. Secondly, the
TiO2 or ZnO penetrate the epidermis, and as a result, the public nanoparticles may be doped with other elements such as man-
health benefits of these nanoparticles were higher than their out- ganese, gallium or cobalt, which will then deactivate the elec-
lined risks. Furthermore, the adverse effects of nanoparticles may trons that have been excited upon UV irradiation (19).
not be attributed to their skin penetration (19). The coating or encapsulation method is based on a protective
film consisting of organic or inorganic material. This protective
film is meant to effectively contain the nanoparticles and thus
Photoreactivity
prevent direct contact between the generated free radicals and
Metal oxides are usually valued for their photocatalytic activity. skin cells. However, in the majority of the organic film-based
However, in the specific case of sunscreens, this particular prop- encapsulation technologies, dangers exist as damage to the film
erty is undesirable. It has been found that the reactive species can occur from external influences such as UVR, environmental
produced due to the photocatalytic activity of metal oxides may hazards and the formulation itself. Inorganic coatings other than
lead to the decomposition of other materials. metal oxides are a viable solution, but their effectiveness can
The photoactivity of TiO2 and ZnO nanoparticles is usually vary based on the thickness of the metal oxide layer. The best
linked to their cytotoxicity and genotoxicity, and both are well- option seems to be doping the crystal lattice with other metals or
known photocatalysts. The photocatalytic activity of TiO2 has the surface with free radical scavenging moieties to reduce the
proved to be useful in the field of environmental waste photoreactivity. However, these are not cost-effective solutions.
788 Orielia Pria Egambaram et al.

The encapsulation of inorganic filters, particularly ZnO and poly(methacrylic acid)-coated particles was more elevated than
TiO2, may be carried out using compounds such as oleic acid or the uncoated nanoparticles and oleic acid-coated ZnO nanoparti-
hexadecylamine, which are both hydrophobic and soluble in cles.
organic solvents (62). It has also been observed that silicon diox- A study by Virkutyte et al. (67) indicated that an increase in
ide acts as a chemically stable shell as it is not able to absorb the chlorine concentration in swimming pools is capable of
light in the visible light region, it is both physically and chemi- depleting the aluminum hydroxide coating found in TiO2-based
cally stable, and it has no toxicological threat (19). There is also sunscreen formulations. It was found that an increased chlorine
information regarding the encapsulation of inorganic filters with concentration shifted the zeta potential from 64 to 8 mV,
polymers, such as PABA, and it was found that these did not which resulted in the formation of unstable TiO2 nanoparticles.
induce the generation of ROS (43). Although designed with good intentions in mind and the
A study in 2007 by Rampaul et al. (63) revealed that TiO2 desire to correct the preexisting issues with sunscreen formula-
nanoparticles doped with manganese or aluminum can provide tions, it has been found that there are drawbacks to coatings and
better skin protection when incorporated into sunscreen. Further formulations as outlined above. To ensure that an even bigger
studies showed that alumina/manganese, alumina/dimethicone problem is not created, cosmetic companies and relevant parties
and aluminum hydroxide coatings are well suited for the use in must ensure that the coatings and formulations are designed to
sunscreen as they can prevent the phototoxicity of TiO2 nanopar- provide a synergistic effect toward protecting the consumer
ticles (43). rather than increasing the amount of harm that they may invoke.
Mitchnick et al. (64) also observed lower levels of photocat-
alytic activity for ZnO nanoparticles when compared to TiO2. In ENVIRONMENTAL IMPACT OF UV FILTERS
this study, the photodegradation of dimethicone, silica coated
and uncoated ZnO and TiO2 nanoparticles was analyzed by test- While the effects of UV filters on the health and safety of the
ing the rate of isopropanol oxidation. The results revealed ele- consumer have been extensively studied, the effect that these fil-
vated photocatalytic levels for the coated TiO2 nanoparticles in ters have on the environment is not as widely researched for the
comparison with the uncoated nanoparticles. In regard ZnO, the simple reason that the environment cannot advocate for itself.
coated and uncoated particles exhibited meager rates of iso- However, given the nature of these filters, it is evident that there
propanol oxidation. The same group in another study also will be some environmental impact created as a result of their
observed more moderate levels of photocatalytic activity for ZnO use by humans.
nanoparticles when compared to TiO2. In seawater samples, UV filters are usually present in a dis-
Formulations, encapsulations, coatings and any other methods solved liquid phase or they may be adsorbed onto particulate
used to decrease the photoreactivity of UV filters need to be able matter present in the sample. Benzophenone-3 (BP3) and 4-
to prevent adverse effects rather than promote them. As such, methylbenzylidene camphor (4-MBC) have lipophilic characteris-
some of the specific characteristics of an ideal formulation are as tics and due to this they are often found on the surface micro-
follows: Prevent nanoparticle aggregation, enhance the photosta- layer in concentrated amounts or accumulated in the soil and
bility of the sunscreen, increase the efficacy of the sunscreen and particulate matter (68).
decrease the cutaneous permeability. Creating a suitable formula- A study by Langford et al. (69) focused on the effect of four
tion is vital because the long-term effects of even a small per- organic UV filters and four organic UV stabilizers on aquatic life
centage of nanoparticle penetration into the skin barrier may in various water systems, wastewater sludge, landfill leachate,
result in significantly larger consequences (50). sediments, marine and freshwater biota. The marine life selected
Coatings can decrease the relative photoreactivity of nanopar- for the analysis included prawn, crab, cod, perch, whitefish and
ticles by isolating it from the skin and thereby minimize the burbot. BP3 was found in 40% of the cod livers in the range of
interactions between the nanoparticles and the skin. Unfortu- 30–1037 ng g 1, while it was present in 53% of prawns within
nately, although providing decreased photoreactivity, these coat- the range of 30–69 ng g 1. 10% Octocrylene (OC) was most
ings cannot completely prevent all photoreactivity. Carlotti et al. prevalent in cod livers with 80% of the cod livers containing this
(65) investigated the overall photoreactivity of coated and UV filter. These results indicate the difference in sensitivity that
uncoated TiO2 nanoparticles. Both forms of TiO2 were present in exists at the different trophic levels. Overall, the results showed
the formulations studied with diameters ranging between 15 and that organic UV filters may pose a risk under low flow condi-
100 nm. Two of the coated compositions were found to have tions. However, there was a minimal risk detected under the con-
induced significant peroxidation. The level of peroxidation was ditions analyzed.
comparable to a commercial brand of uncoated TiO2 (Aeroxide A similar study was conducted in 2015 by Sanchez et al. (68)
P25). Overall, it was found that silica was the most stable and in the Canary Islands, which is a budding tourist attraction year-
efficient coating. round due to the favorable weather conditions. The study
In 2010, Yin et al. (66) investigated the effects of the surface focused on eight common organic UV filters. The aim was to
chemistry of ZnO nanoparticles on the cytotoxicity, genotoxicity determine the content of UV filters in seawater samples collected
and generation of ROS. During this study, they used ZnO from six different beaches and compare the quantities. The study
nanoparticles with diameters of ~30 nm and an array of coatings. revealed that 99% of the samples contained UV filters at relative
After 24 h, they found that the viability of human lymphoblas- quantities which present an overall risk quotient of >10. The
toid cells had decreased substantially and these results were simi- results showed that all six beaches had similar profiles with BP3,
lar to the results obtained for the uncoated particles. OC and butyl methoxy dibenzoyl methane (BMDBM) present in
Furthermore, they found that the oleic acid-coated particles exhi- the highest quantities. Ultimately, the results showed that the use
bit higher levels of cytotoxicity and ROS generation when com- of sunscreen directly linked to high tourist influx posed signifi-
pared to the uncoated ZnO nanoparticles. The genotoxicity of cant potential for adverse effects on the aquatic life.
 Photochemistry and Photobiology, 2020, 96 789

There is an astounding amount of evidence present to suggest is no surprise that coral is most susceptible to global change and
that the bioaccumulation of organic UV filters is occurring within anthropogenic impacts. The effect of inorganic UV filters,
food webs. These organic filters have been found in several namely ZnO and TiO2, on coral reefs is observed mainly through
aquatic organisms such as mussels, crustaceans, fishes and mar- their symbiotic microalgae (75). It has been found that uncoated
ine mammals. Organic filters are lipophilic and thus collect ZnO nanoparticles can permanently bleach corals, which ulti-
within the adipose tissue and muscles of these animals. A partic- mately results in the widespread mortality of the zooxanthellae
ular example includes traces of octocrylene (OC), which were of stony corals. This, in turn, promotes the microbial enrichment
discovered in the liver of a dolphin species off the Spanish coast. around the coral. It is believed that this bleaching is due to
Furthermore, there has been the discovery of up to 7112 ng g 1 changes in the cellular membrane lipid of the corals.
dry weight (d.w.) OC present in mussels, which were retrieved In comparison, manganese-modified TiO2 has a significantly
off of the French coast (70). lower effect on coral and this may be due to the reduction in the
A recent study in Brazil by Mollins-Delgado et al. (71) reactivity of TiO2 due to its coating (76). Ultimately, the use of
focused on the presence of UV filters within Mugil liza, a popu- sunscreens containing UV filters affects stony coral.
lar fish species found in Brazil with grave economic importance. An environmental risk review published in 2015 indicated that
The study analyzed various parts of the fish including the mus- the generation of ROS by inorganic UV filters such as TiO2 has
cle, gills and liver tissue, which were all analyzed separately. a toxic effect on marine phytoplankton, which is usually the case
Overall, the total accumulation value of the UV filters within the for uncoated TiO2. However, even though some TiO2 may be
fish was between 176 and 631 ng g 1. It was found that the fil- coated, the coating may be dissolved in an aquatic environment
ters were mostly accumulated within the liver, which exhibited rendering photoactive TiO2 nanoparticles, which can evoke toxi-
eleven times higher accumulation than the muscle and five times cological effects in a marine environment (70). It has been found
higher accumulation than in the gills. This particular fish species that the specific phototoxicity of nanosized TiO2 is specifically
is often preyed on by predators such as dolphins, and thus, the toxic toward the crustacean, Cladocera. This study employed a
biomagnification and overall impact on the food web are inde- phototoxicity ratio wherein the experiments were performed in
scribable. Mugil liza may be consumed up to 25 g per capita in the presence and absence of sunlight.
Brazil. Assuming a 68 kg person were to eat this stipulated In 2005, the United States Environmental Protection Agency
amount of fish, he/she may be susceptible to a daily intake (EDI) estimated that the amount of nano-TiO2 produced globally was
of 0.3–15.2 ng/(kg body weight) of UV filters from fish muscle 2000 tons (30). Based on an industry survey carried out in 2012,
and an EDI of 9.2–64 ng/(kg body weight) from the consump- an estimation by Piccinno et al. (77) was that between 2006–
tion of 25 g of liver. 2010, 550–5500 tons of nano-TiO2 was produced per year. This
Coral reefs in particular are the most susceptible to the effects group also estimated that approximately 55–550 tons of nano-
of sunscreens and their degradable by-products. As of 1 January ZnO particles were produced per year. It is believed that 60% of
2021, all sunscreen products containing oxybenzone and OMC nano-TiO2 and up to 80% of nano-ZnO were used in cosmetic
will be banned in the state of Hawaii. This has come after several formulations, namely sunscreens. These nanoparticles can infil-
studies and investigations on the long-term effects of sunscreens trate the marine environment at any point during their production
on coral reefs. Oxybenzone and OMC are the main ingredients in life cycle, including air deposition (70). Once they reach the
up to 80% of all sunscreen and personal care products sold world- marine environment, they can induce severe damage to marine
wide (72). Evidence to support the legislation regarding the ban- life including an endocrine disrupting function and the overregu-
ning of sunscreen can be found in three main studies: lation of specific genes.
The Old Danube Lake in Vienna is ~1.6 km2 and a favorite place
• Several species of coral around the world were studied by
for water sports and recreational activities. Gondikas et al. (78)
Danovaro et al. (73), and it was found that all of the sampling
speculated that due to the high influx of recreational activities, an
sites contained traces of sunscreens, which were responsible
estimated 8.1 tons per year of sunscreen is used at the lake resulting
for dose-related (≥10 µL L 1) and temperature-related
in ~94.5 kg of TiO2 being deposited into the lake annually. Given
(≥30°C) bleaching of the corals (70). Bleaching is the process
the bioaccumulation over time in sedimentation and aquatic life, the
of expelling algae from the coral and is a clear indicator that
long-term effect on the overall ecosystem may be severe.
the coral is under stress and in impending danger of dying.
• In 2017, Stein et al. (74) published a study based on the cellu-
In 2010, Miller et al. (79) investigated the effects of inorganic
UV filters on phytoplankton. The group found that nano-ZnO
lar toxicity of OMC, mainly focusing on the major photo-in-
present at 0.5–1.0 mg L 1 was able to inhibit the growth of four
duced products of this UV filter. It was found that when
phytoplankton species. Nanosized TiO2 was also analyzed at this
exposed to UVR, OMC degrades rapidly to produce two
concentration and exhibited no effects. Simulated solar exposure
major cyclodimers (d-truxinate and a-truxillate). The study
of nano-TiO2 increased the phototoxicity of the particles up to
revealed that the parent compound, OMC, as well as the two
four times as per a study by Ma et al. (80), ultimately rendering
cyclodimers was highly toxic.
• The effects of oxybenzone on the larval form of various coral
D. Magna 100 times more sensitive to nano-TiO2 than Oryzias
latipes. Jacobasch et al. (81) studied the effects of long-term
species were studied by Downs et al. (45) The group also
exposure to uncoated nano-TiO2 on cladoceran D. magna and
investigated the overall toxicity in vitro on six other species of
found that chronic exposure up to 1.78 mg L 1 resulted in com-
coral. The median lethal concentration (LC50) values for the
plete mortality over a 6-generation case study. Chen et al. (82)
larval form that were exposed to oxybenzone for 24 h ranged
conducted a similar study in D. rerio (zebrafish) over six
from 139 to 779 µL L 1.
months. It was found that nano-TiO2 resulted in organ injury and
The role of our coral reefs in balancing our ecosystem often mortality due to the bioaccumulation of nano-TiO2 in the brain,
goes unmentioned until these reefs are under threat. However, it gills, liver and heart.
790 Orielia Pria Egambaram et al.

Very recently, the European Commission also raised concerns Despite the SPF reading, sunscreens must be reapplied
over the UV filters from personal care products that are toxic, throughout the day to provide maximum protection. The reappli-
persist in the environment and accumulate in the bodies of cation of sunscreen will replenish the sunscreen, which may have
organisms that take them in (83). UV filters are now considered been lost during swimming and sweating, and even wiped off by
as important organic contaminants in the aquatic environment clothing or a towel. Dr K. Mallet, a clinical director for skin can-
due to the bioaccumulation and proven/potential endocrine dis- cer and alcohol projects and a research associate in the Preven-
rupting effects on some species and humans (84). The European tion Research Center in the College of Health and Human
Chemicals Agency (ECHA) has included oxybenzone in its com- Development, stated that sunscreen should be applied in decent
munity rolling action plan (CoRAP) because of its potential amounts at least 30 min prior to going into the sun. Sunscreen
harmful effects, while OMC has recently been removed from a should then be reapplied every 1–2 h throughout the day, or dur-
watch list of potential water pollutants, as sufficiently high-qual- ing sun exposure to compensate for the sunscreen layer having
ity monitoring data are now available (85). In a study, seven UV been washed off or depleted (88).
filters including oxybenzone and OMC with potential endocrine Research indicates that in reality, most people use
disrupting properties were found at low levels in the eggs of <2 mg cm 2, which is the stipulated amount used during the
seven wild bird species in the national park, Spain, highlighting SPF testing of sunscreens. In New England, a study was con-
the need for a risk assessment regarding the bioaccumulation and ducted on beachgoers, which indicated that on average
biomagnification of UV filters in the environment leading to the 0.5 g cm 2 was applied and areas such as the back, sides of the
exposure of wildlife and humans (86). neck, and ear often have little to no sunscreen applied. Usually,
The overall effect of UV filters on the environment is hard to inorganic sunscreens are used less frequently and in lower
quantify. Once they are released from sunscreen products, these amounts due to the whitening effect caused by the presence of
filters may be distributed into different facets within the environ- ZnO and TiO2. A study showed that 66% less inorganic sun-
ment such as wastewater, seawater, biota and sediments. Given screen was applied than organic sunscreen in a group of 25 vol-
the limited understanding of the impact of these filters, we can- unteers. It has thus been found that the daily application of
not conclude that there are no long-term effects on the food web sunscreen is more effective in protecting the consumer than inter-
due to bioaccumulation. More studies must be carried out to mittent applications. Individuals who are expected to have multi-
ensure that the agents aimed to protect humans are not, in turn, day sun exposure should use higher SPF sunscreens because this
degrading our environment. has been found to decrease the sun sensitivity to UVB (17).
The literature describes SPF as the time is taken for one to
burn without sunscreen divided by the time it takes to burn with
UV FILTERS EFFICACY AND ADAPTED
sunscreen, given that all other factors remain constant. Therefore,
TESTING METHODS FOR SUNSCREENS SPF = minimal erythemal dose of protected skin/minimal erythe-
The SPF mainly determines the efficacy of sunscreen agents. mal dose of unprotected skin. Typically, it may be assumed that
This concept was introduced in the 1960s by Franz Greiter an SPF 50 sunscreen will provide 50 times more protection than
from Switzerland, and the value indicates the number of multi- with no sunscreen at all. A sunscreen with an SPF of 30 typi-
ples of the minimal amount of UV radiation that you can cally allows 3.33% of erythemally effective UVR to pass through
absorb while using the sunscreen before becoming sunburned the sunscreen layer and cause sunburn, while SPF 50 is expected
(10). He proposed a way to measure a sunscreens’ efficacy in only to allow 1.67% to pass through the thickness of sunscreen
suppressing sunburn, which is usually brought on by overexpo- and evoke sunburn. Overall, the effectiveness of sunscreen
sure to UVB radiation by determining the ratio between the agents is measured using the SPF and substantivity. The substan-
amount of UVR required to cause the protected skin to burn to tivity is the property of continued remedial action despite the
the amount of UVR required to burn unprotected skin, while vehicle responsible being removed (11).
all other factors remain constant. The SPF typically evaluates Most of the published test methods adopt an in vivo method
the protection against sun damage mainly caused by UVB based on measuring the MED on human skin, which is very
(280–315 nm) and UVA2 (315–340 nm) (87), and the higher time-consuming and expensive. The International SPF test
the SPF value, the greater the protection against the hazardous method 2006 (COLIPA CTFA CTFA-SA-JCIA U.S.), ISO
effects of sunlight on the skin. Unfortunately, the SPF value 24444:2010 (E), FDA Final Rule 2011 and AS/NZS 2604 are
does not indicate the degree of protection that the product globally established methods in the field of SPF in vivo testing,
offers against UVA1 (340–400 nm). Given that the effects of which use the same general approach. However, two widely
UVA are known to be harmful, the need for a UVA protection accepted standard methods currently used for SPF determination
factor is apparent. are ISO 24444:2010 and US FDA 2011. The slight differences
To obtain the desired SPF value to offer maximum sun pro- between the ISO and FDA methods have no influence on the
tection to the consumer, formulators often combine a variety of results, and hence, the SPF values obtained using the two meth-
inorganic and organic UV filters. An example of the active ods are comparable (89).
agents present in a popular sunscreen brand in Europe used in There are currently three methods available used for in vivo
the 1990s was as follows: 4-methylbenzylidine camphor (6%), UVA protection evaluation: immediate pigment darkening (IPD),
avobenzone (2%), ecamsule (2%) and TiO2 (5%) (20). The com- persistent pigment darkening (PPD), and UVA protection factor
bination of filters may influence various factors, such as the pen- (UVA-PF). IPD and PPD are only based on the immediate
etration of UV filters in the stratum corneum, and this may also changes in pigmentation, which is caused by UVA irradiation.
affect the photoreactivity of the particles within the formulation, UVA-PF evaluates the minimal erythematous response and per-
which are not reflected in the SPF value. manent pigmentation, which is caused by UVA irradiation (87).
 Photochemistry and Photobiology, 2020, 96 791

Persistent pigment darkening, which was developed in Japan, obtained results, which therefore makes the reliability of these
is usually used to measure the protection that the sunscreen pro- results questionable (87).
vides against radiation within the UVA range. There are certain Another SPF in vitro method used for sunscreen testing is a
drawbacks to this technique though. It is often not carried out on method developed by the National Institute of Public Health
skin types which are more susceptible to damage by UVR: skin (NIPH). This method employs the use of artificial substrates and
type 1. The clinical impact of PDD below 320 nm is indistinct a double beam UV spectrophotometer. Here, the attenuation of
(11). the UVB intensity is measured on a sheet of Mikelanta covering
Immediate pigment darkening focuses on the pigmentation the paper with 2 mg cm 2 of the desired sunscreen applied to
changes that occur within 2–24 h following UVA irradiation. the paper. The irradiation source used during this method is a
Here, the measurement of the lowest UVA dose required to pro- UVA/UVB source (87).
duce a darkening of the skin upon UVA irradiation (87). Unfor- Limitations of in vitro methods include the lack of standard-
tunately, this method lacks accuracy as it is difficult to obtain ized international agreed testing protocols, difficulty in evaluating
highly reproducible results and the obtained results have a high the water resistance of sunscreen formulations, inconsistencies
degree of variation between them. The results obtained are for that can arise upon applying the formulations on the substrate, as
low doses of UVA irradiation and the test is usually conducted well as the fact that it works only for formulation containing fil-
on skin types III and IV (11). Furthermore, in vivo testing does ters with UVR absorption properties as the principle is based on
not factor in the effect of visible light, which is much higher the % transmittance of UVR.
than that of solar UVR in producing skin erythema.
Although widely accepted and used, there can be interlabora- REGULATIONS AND SAFETY PROTOCOLS
tory SPF variability in in vivo testing that must be related to
uncontrolled testing variables such as the technique used to Several sunscreen labels have been known to have misguided
spread the product on the skin (pressure and duration variables), information, which is ultimately detrimental to the consumer.
test subject sensitivity, and variability in the observation and Therefore, the need for specific guidelines to assist consumers is
determination of the biologic endpoint, MED response. Genetic of paramount importance. These guidelines are specific to certain
variability in the test subjects across the globe is also factors countries, but the main aim is to protect the consumer and the
contributing to this problem (90). general public.
With regard to in vitro evaluation, three methods are widely In the United States, the use of sunscreens and the regulation
employed: the FDA method, COLIPA method (European Union) surrounding them is governed by the FDA. Sunscreens in the
and Boot star method (United Kingdom). The FDA method United States are classified as “over the counter drugs” (OTC)
employs the use of a critical wavelength method by which the and thus may only be purchased from “drugs stores” or pharma-
UV transmittance through a sunscreen film is measured. The crit- cies with the correct prescription. In this way, there is greater
ical wavelength is a measure of the absorbance across the entire control on the release of these products into the market and pro-
UV spectrum (UVA & UVB). For a particular product, the criti- tects consumers from misguided information, which may have
cal wavelength is defined as “the wavelength where the area been on the product. By labeling sunscreens as OTC products,
under the absorbance spectrum for the irradiated product from there has been a higher demand for safety data, which has ulti-
290 nm to the critical wavelength is 90% of the integral of the mately resulted in the banning of certain products due to the lack
absorbance spectrum from 290–400 nm”. Hence, the critical of such information. Furthermore, the Sunscreen Innovation Act
wavelength for a UVB sunscreen will be <320 nm, while a established in 2014 focuses on the properties of UV filters,
UVA & UVB sunscreen would have a critical wavelength including their safety data and ultimately determines whether
between 320–400 nm (87). they are permitted for the US market (91,92).
The Boots star rating was established in 2011. This method According to FDA guidelines, both UVA and UVB protec-
measures the UVR transmittance through a film of sunscreen and tion must be tested before the protection factors are reported.
the measurement is performed using polymethylacrylate Hence, to be labeled as a “broad-spectrum” sun protecting
(PMMA) plates. The absorption of a 1 mg cm 2 film is mea- agent, the product must possess a critical wavelength of at least
sured between 290 and 400 nm. The samples must be preirradi- 370 nm. However, the critical wavelength and the SPF value
ated. This measurement provides the ratio between the average are not sufficient to provide a full measure of the products
UVA and UVB absorbance, and this is measured pre- and postir- broad-spectrum sunscreen capabilities. As a result, the European
radiation (87). Commission recommended that all sunscreen products have a
The FDA method is currently the proposed method for testing SPF/UVA-PF ratio of ≤3 and their critical wavelength needs to
within the United States. This method involves the transmittance be at least 370 nm to exhibit an adequate level of protection
of UVR through a sunscreen film (0.75 mg cm 2) and the mea- (87,90,93).
surement is recorded between 290 and 400 nm. The critical In the European Union the overall safety is governed by the
wavelength method is used. The samples require preirradiation EU Scientific Committee on Cosmetic and Non-Food Products
for this measurement (87). intended for Consumers (SCCNFP). As per the current EU regu-
The SONING method was introduced in 2001. This method is lations, sunscreens are considered cosmetics as they are placed in
widely used and involves the use of tracing paper, a UVB source contact with external body parts to protect the skin from damage
and PMMA plates. 2 mg cm 2 of the sunscreen product is due to overexposure to sunlight. As a cosmetic, sunscreens in
placed on a roughened PMMA plate, which is then exposed to a the EU are evaluated by the Scientific Committee on Consumer
UVB source. There have been recent discoveries that the indices Safety (SCCS), which provides recommendations regarding the
obtained from the UVA to UVB ratio as well as the critical health and safety risks that these products may pose to
wavelength contain high amounts of variation between the consumers (91,93).
792 Orielia Pria Egambaram et al.

As per the commission recommendations, testing and labeling To the average consumer, the method of SPF determination
of sunscreen products within the EU are governed by stringent and scientific detail is irrelevant and most certainly not common
guidelines. These guidelines are focused on specific labeling knowledge. The labeled SPF value is determined as per FDA
warnings, the ratio of UVA and UVB protection, and the catego- standards due to the application of a 2 mg cm 2 layer of sun-
rization of products as per the range of protection offered. Some screen. However, it has been found that the average consumer
of the guidelines include the following: a minimum SPF value of only applies a thickness of ~0.5 mg cm 2 and the sunscreen is
6, UVB protection must be three times UVA protection, the criti- not applied frequently enough to elicit adequate protection (95).
cal wavelength used for testing must be greater than 370 nm, Furthermore, a study in 2002 conducted in Queensland, Aus-
and the testing of the product must have been according to an tralia, sought to better understand the sunscreen application pat-
approved in vitro SPF/UVA method. Only once the product has terns of a randomized group of participants in the area in an
complied with all the guidelines will they be provided with the attempt to further assist skin cancer prevention strategies. There
UVA seal (91,93). was no simulated situation, and each participant was instructed
Australia has the highest incident levels of skin cancer in the to apply sunscreen daily regardless of the weather conditions or
world, and thus, the use of sun protection agents is quite wide- the activities they had planned for the day. It was found that
spread. As a result, the sunscreen regulations in Australia are approximately 1.5 g of sunscreen was applied per day with an
quite stringent. Sunscreens in Australia are classified as either average of 0.79 g cm 2 applied to the skin. It was discovered
cosmetic or therapeutic goods. Cosmetic sunscreens, which are that ~50% of participants did not believe that it was necessary to
typically secondary sunscreen (up to SPF 15), contain ingredients use sunscreen daily despite the harsh weather conditions and
that can provide sun protection, but the main claim is not to pro- high skin cancer prevalence in their area (96).
vide sun protection. Examples of cosmetic sunscreens include The SPF reading of a sunscreen is mainly focused on the pro-
lipsticks which provide UVR protection, moisturizers containing tection from UVB although some protection from UVA is also
sunscreens with an SPF up to 15, or products containing sun- provided. It is known that UVB is more carcinogenic than UVA,
screen agents as a secondary function. The purpose of formula- and as a result, an increase in protection against UVA may lead
tions which have an SPF of >15 (primary sunscreens) is to to a reduction in protection against skin cancer. As the SPF is a
protect from UVR (93,94). measure using solar simulated radiation rather than natural solar
The Therapeutic Goods Administration (TGA) classifies thera- radiation, in addition to the poor coverage of sunscreen, the sta-
peutic sunscreens. Therapeutic sunscreens with an SPF value of ted SPF may offer less protection than anticipated by the con-
>30 may have an array of indications on their label, which may sumer (5). Consumers are misinformed or often under informed,
include; “can aid in the prevention of sunspots” and “may reduce and they are usually unaware that a specific amount of sunscreen
the risk of some skin cancers.” For sunscreens with an SPF of must be applied to provide adequate protection, which usually
<15, they must be able to claim broad-spectrum protection. The renders consumers vulnerable and unfortunately sunburnt even
use of nanosized zinc oxide and titanium dioxide in sunscreens after the application of sunscreen. As sunscreens do not often
is common, and in Australia, the particle size specifications are provide any moisturizing benefits, consumers should always be
not required for labeling (94). Furthermore, UVA protection in advised to apply sunscreen on top of a moisturizer to prevent
Australia is defined as a compound that can transmit <10% of dehydration of the skin due to UVR exposure.
sunlight between 280 and 320 nm. SPF 50+ is the benchmark for As mentioned previously, each country has a specific author-
sunscreen in Australia, and there are very high restrictions in ity and set of regulations governing the use of sunscreen prod-
regard to the term “water resistant,” if this is stated on a sun- ucts. Although in vitro evaluation for the determination of the
screen product, it must be accompanied by strict guidelines SPF is internationally preferred, the specifics of the methods
regarding the lifestyle use thereof (11). used differ between countries. Therefore, it is hard to place a
In Japan, the Ministry of Health approves the sunscreens definitive mark on the specific way in which sunscreens will be
available. The UV filters used in sunscreens are subject to strin- tested. As a result, the data obtained from studies in different
gent scrutiny, and only after specific bodies have approved them, countries differ significantly, which makes the overall study con-
are they available to consumers. The regulatory guidelines moni- troversial.
tor the amount of product that must be applied, the time required The reports regarding penetration, photostability and photore-
to measure the minimal persistent pigment darkening, and the activity are quite controversial, and therefore, it is not quite pos-
dose of radiation (91,93). sible to make a definitive conclusion regarding the overall safety
Similarly, in Taiwan, sunscreens are considered to be medi- of specific sunscreen active agents or UV filters. The difference
cated cosmetics, and they must have specific registration and in the results reported is often due to the lack of standardized
labeling. As per South African legislation, sunscreens are consid- testing methods. There is also a lack of full physiochemical char-
ered as cosmetic products and they must comply with ISO acterization of commercially available nanoparticles and this neg-
24443 for UVA photostability testing (93). atively influences any experimental design which may be created
for the testing of the nanoparticles in the future.
To date, there have been no new developments toward the
CHALLENGES
formation of an internationally accepted sunscreen regulatory
The effects of overexposure to sunlight, which may lead to sun- method, which will be employed in all countries globally. With-
burn, photoaging and skin cancer are widely known, and the reg- out a validated method, which is consistent throughout the coun-
ulatory authorities are doing their best to improve awareness. tries, the safety of sunscreen products is still subjective. Further
However, there is still some skepticism about the use of sun- research should be conducted on the size optimization of
screens due to the health risks associated with them and the nanoparticles to prevent skin penetration and the prevention of
actual efficacy of the products. the formation of ROS.
 Photochemistry and Photobiology, 2020, 96 793

Sunscreens and sun care products are highly expensive, espe- (Hedera helix) showed active UVR extinction and excellent visi-
cially in developing and underdeveloped countries. As a result, ble transparency along with significantly lower toxicity than
sunscreen is not used regularly enough and when used it is used TiO2 and ZnO nanoparticles (109). The prospects of natural clay
sparingly, which may not even provide adequate protection. minerals in UVR protection and synthetic clay minerals with
reduced photocatalytic activity for sunscreen application have
been highlighted recently (109,110).
NEW DEVELOPMENTS
In summary, many achievements have been reported towards
Addressing the materials science challenges in sunscreen devel- the development of new inorganic filters to overcome aesthetic
opment for topical application, a lot of research has been focused drawbacks, skin penetration and photoreactivity. However,
toward advanced physical filters that are more efficient and safer despite all these efforts, TiO2 and ZnO remain the industry
not only for the health of users, but also for the environment, favorites, which may be due to their acceptance by the regulatory
which can be used as a substitute for TiO2 or ZnO in future anti- bodies, cost-effectiveness, and nonirritant nature.
UVR formulations.
Recently, natural sunscreens have been of particular interest
CONCLUDING REMARKS
as they may provide protection from solar radiation without
compromising the safety of the consumer. Baker et al. (97) Given the heightened warnings from dermatologists globally on
evaluated the topic of photoprotection looking at natural sun- the dangers of overexposure to UVR, it is evident that we
screens and the design of certain artificial sunscreen con- require sun protection for our skin. The question then becomes
stituents. Organisms are known to contain natural sunscreen whether we should opt for sunscreens containing organic or inor-
molecules, which are often found close to the surface, protect- ganic filters, which is safer, and which is more effective?
ing vital organs. These molecules can provide protection by Organic UV filters are chemical substances that protect by
exhibiting the high absorption of incident UVR and are able to absorbing UVR, but several studies have shown that due to their
dissipate absorbed photon energy without compromising the low lipophilicity, they can cross the skin barrier, which then ren-
molecular integrity of the organism. One such molecule is lig- ders them able to penetrate viable skin cells and cause deleteri-
nin, which is found in most vascular plants and occurs abun- ous effects.
dantly throughout the earth. Mammalian DNA/RNA With regard to inorganic filters, the concerns regarding the
components such as adenine, thymine, guanine, cytosine and use of inorganic nanoparticles as filters are legitimate. A substan-
uracil are all photostable and can provide protection similar to tial number of tests have been conducted to determine the effi-
that of a sunscreen. cacy and toxicity of these particles. The downfall to this is that
Mycosporine-like amino acids (MAAs) have also sparked the tests were not conducted under standardized conditions,
recent interest for their potential use as a natural sunscreen. which mean that they may not be comparable. Furthermore, with
Their mechanism of protection against photo-induced aging on regard to the use of in vivo testing, it was found that the tests
mice was investigated by Ying et al. (98). It was found that were conducted on different species, each with varying degrees
MAAs were able to inhibit the reduction of endogenous antiox- of penetration for these nanoparticles. However, despite the dif-
idant enzymes, which in turn suppressed UV-induced photoag- ferences in the species used, it was found that none of the tests
ing. reported traces of nanoparticles in viable cells. The current
Hydroxyapatite, one of the components of bone tissue, has weight of evidence shows that nanoparticles remain on the sur-
been found to be a highly effective physical UVR screening face of the skin and on the stratum corneum, which poses no
agent. Its function as a SPF booster, which reduces the concen- toxicological threat to anyone using these sunscreens. To date,
tration of chemical UV filters, has been reported (99). It is also few studies have been able to simulate a real-life scenario for the
suggested that the UVR absorption of hydroxyapatite can be fur- application of sunscreen. Unfortunately, due to differences in
ther enhanced upon doping with Zn2+ and Mn2+ ions (100). Tri- UVR intensity as per geographical locations, there is no standard
calcium phosphate Ca3(PO4)2 is another promising material, protocol for the testing of sunscreens using natural solar radia-
which is nontoxic, nonmutagenic and nonirritating (101). How- tion. The photoreactivity of nanoparticles used in sunscreen
ever, it has a limited UVR absorption capacity unless doped with remains a significant cause for concern. Till the development of
metal ions such as Fe3+ (102). CeO2 nanoparticles appear to be such, and furthermore the standardization of testing of these fil-
another inorganic UV filter. Although CeO2 manifests inferior ters, it may be concluded that the currently available organic and
photocatalytic activity when compared to zinc and titanium inorganic UV filters have safety concerns and more effective
oxide, it still has considerable catalytic behavior toward the oxi- options in UV filters should be developed. There is a high
dation of organic compounds, which make it incompatible with demand for new inorganic UV filters from the personal care
cosmetic products (103). The reduced photocatalytic activity of industry that better address broad spectrum UV protection,
CeO2 doped with cations such as Ca2+, Sr2+, Ba2+, Mg2+, Zn2+ increase the photostability, provide safety with fewer side effects
has been demonstrated (104,105), of which Ca2+ exhibited and no skin permeability.
improved UVR screening along with nearly no photoreactivity With regard to the effects on the environment, it is quite
(106). CePO4 with excellent morphological characteristics, high challenging to provide a final conclusion. There is no doubt
UVR absorption features, low toxicity, low photocatalytic activ- that the use of sunscreens containing UV filters does indeed
ity and ideal particle size for application in sunscreen formula- affect the environment, from the coral reefs to marine life, we
tions that can substitute the currently employed inorganic UV so dearly love. Further studies must be conducted to accurately
filters ZnO and TiO2 have also been reported (107,108). determine the impact that we, as consumers, have on our beau-
Nanoparticles extracted from the hairy rootlets of English ivy tiful planet.
794 Orielia Pria Egambaram et al.

19. Fajzulin, I., X. Zhu and M. M€oller (2015) Nanoparticulate inorganic

Acknowledgements—This work was supported by the National Research UV absorbers: a review. J. Coatings Technol. Res. 12, 617–632.
Foundation (Grant No. 100849) in collaboration with the Department of 20. Serpone, N., D. Dondi and A. Albini (2007) Inorganic and organic
Science and Technology, and Council for Scientific and Industrial UV filters: Their role and efficacy in sunscreens and suncare prod-
Research (National Centre for Nanostructured Materials), Project ucts. Inorganica Chim. Acta. 360, 794–802.
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 Photochemistry and Photobiology, 2020, 96 797

AUTHOR BIOGRAPHIES
Suprakas Sinha Ray is
Orielia Pria Egambaram Chief Researcher in Poly-
received her Bachelor of mer Nanocomposites at
Science Degree and Hon- the Council for Scientific
ours degree from the and Industrial Research
University of Pretoria in (CSIR), Pretoria, South
2014 and 2015, respec- Africa. He was awarded a
tively. She completed her PhD in physical chemistry
MSc in Chemistry in by the University of Cal-
2018 from the University cutta in 2001 and is Man-
of Johannesburg while ager of the Centre for
working at the Centre for Nanostructures and
Nanostructures and Advanced Materials,
Advanced Materials, Department of Science
based at the CSIR. She is and Innovation-CSIR
currently pursuing a Ph.D Nanotechnology Innova-
in the field of renewable tion Centre. He is also
energy at the University affiliated with the Univer-
of Kent. She was a recipient of an NRF Scarce Skills Masters Scholar- sity of Johannesburg as a
ship (2016) and a Vice-Chancellor’s Scholarship from the University of Distinguished Visiting
Kent and is also a member of the Golden Society (UP Chapter). Professor of Chemical
Sciences. Prof. Ray’s current research focus is on advanced nanostruc-
tured materials and their applications.
Sreejarani Kesavan Pil-
lai is a Principal
Researcher at the Centre
for Nanostructures and
Advanced Materials,
Council for Scientific and
Industrial Research
(CSIR), Pretoria, South
Africa. She obtained her
PhD in physical Chem-
istry from Cochin Univer-
sity of Science and
Technology, Kerala,
India, in 2003 and joined
CSIR in 2007. Her cur-
rent research interest is on
nanostructures, delivery
systems and emulsions for topical and active packaging applications.