Pharmacogn. J.

Review Article
A multifaceted peer reviewed journal in the field of Pharmacognosy and Natural Products
[Link]/phcogj

Sunscreens: A review
Mukund Manikrao Donglikar1 and Sharada Laxman Deore2*

Department of Pharmaceutical Sciences, Shri Jagdish Prasad Jhabarmal Tibrewala University, Vidyanagari, Jhunjhunu, Rajasthan–333001, INDIA.
1

Department of Pharmacognosy and Phytochemistry, Government College of Pharmacy, Amravati-444604, Maharashtra, INDIA.
2

ABSTRACT
Sunlight despite of source of life and energy creating major health chal- Key words: UV rays, SPF, COLIPA, IPD, PPD, ISO, Polyphenols, Antioxi-
lenges like sunburn, pigmentation, wrinkles, dermatitis, urticaria, ageing, dant.
immune-suppression and number of skin cancers too. Sun protective
clothes and or sunglasses provide insufficient and less convenient Correspondence:
approach to get rid of all these health hazards. So sunscreen protection Sharada Laxman Deore,
is popular mean among various regions of world. Present article have Department of Pharmacognosy and Phytochemistry,
summarize types and classification, regulations, terminologies, evalua- Government College of Pharmacy, Amravati-444604 Maharashtra, INDIA.
tion methods, labeling, dosage and controversies of sunscreens. Natural Phone no: 91-9766577646
chemical classes like phenolics (tannins, flavonoids), carotenoids, vita- Email: sharudeore_2@[Link]
mins, oils are also discussed. DOI : 10.5530/pj.2016.3.1

INTRODUCTION
In India, cosmetic is defined as any article intended to be rubbed, poured, skin problems like cracks, burns, immune suppression, wrinkles, derma-
sprinkled, or sprayed on, or introduced into, or otherwise applied to the titis, urticaria, ageing, hypopigmentation, hyperpigmentation and most
human body or any part thereof for cleansing, beautifying, promoting complicated skin cancers.11 Role of infrared radiations in skin damage
attractiveness or altering the appearance, and includes any article is unclear.
intended for use as a component of cosmetic.1 Now-a-days one cosmetic
product category sunscreen have gain wide popularity due to additional Mechanism of photoreaction
health benefits apart from beautification.2-3 Either separate sunscreens or Photo-oxidative mechanism depending on light-driven reactive oxygen
many other sunscreen loaded cosmetic products for skin care, hair care, species (ROS) generation is now accepted to cause skin photoaging and
lips care and eye care are available in market.4-7 This review is tried to photocarcinogenesis.12 UVA rays mediated photo-oxidative damage
summarize all possible issues related to sunscreens. effectively reaches through the upper layers of skin into the human dermis
and dermal capillary system. Substantial protein and lipid oxidation
Ultra-Violet radiations and human skin8-9 occurs in human skin epidermis and dermis together with a significant
Ultraviolet (UV) radiation is defined as that portion of the electromag- depletion of enzymatic and non-enzymatic antioxidants in the stratum
netic radiation lies between X-rays and visible light which is from 200 to corneum, epidermis and dermis. The immediate as well as persistent
400 nm. This ultraviolet radiation comprises 3 categories depending on pigment darkening (IPD or PPD) responses of human skin are due to
wavelength as follows: photo-oxidation of pre-existing melanins and its precursors respectively.
• UV-A Radiation: This radiation ranges between 320 to 400 nm. Also up-regulation of hemeoxygenase-1 (HO-1), ferritin, glutathione
UV-A is most responsible radiation for immediate tanning or dark- peroxidase, Cu–Zn-dependent superoxide dismutase (SOD1), manganese-
ening of the skin due to excess production of melanin in the epidermis, dependent superoxide dismutase (SOD2), and catalase occurs after solar
premature photo ageing, suppression of immunologic functions, irradiation.13
and even necrosis of endothelial cells and damage of dermal blood UV rays contact initiates photo oxidative reactions to activate protein
vessels. kinase C enzyme and reactive oxygen species which further reacts
• UV-B Radiation: This radiation ranges between 280 to 320 nm. with protein lipids and DNA to form cyclobutane pyridine dimmers.
UV-B radiations are known as burning rays as they are 1000 times This leads to erythema, edema, skin sunburn and cell apoptosis. UV
more capable of causing sunburn than UV-A. UV-B rays act mainly irradiation activates cell surface growth factor and cytokine receptors on
on the epidermal basal cell layer of the skin but more genotoxic keratinocytes and fibroblasts in human skin, critical in the regulation
than UV-A radiations. Ultraviolet B (UVB) rays vary with time and of cell proliferation and survival.14 UV-driven formation of H2O2 regu-
season are major cause of sunburn. Sunburned skin is a leading risk lates the tyrosine kinase activity of the epidermal growth factor receptor
factor for melanoma and non-melanoma skin cancer. (EGF–R) and emerging evidence suggests the inhibition of protein
• UV-C Radiation: This radiation ranges between 200 to 280 nm. tyrosine phosphatases as a consequence of UV-induced ROS formation.
UV-C radiations are filtered by stratospheric ozone layers so less According to response to sun radiation Fitzpatrick’s skin type classifica-
effective and hazardous. tion15 is most popular for decision of types of skin:
The human skin is the largest organ of the body of surface area of
approximately 1.5–2.0 m2. Skin acts as effective barrier against the Protection:
harmful effects of environmental and xenobiotic agents.9-10 Among all Use of physical barriers16 to sunlight like sun protective clothing, sun-
factor chronic exposure of UV radiations is key factor in instigation of glasses, hats, umbrella, shade and possible avoidance of sunlight can be

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 DONGLIKAR AND SHARADA.: Synthetic and natural sunscreen

Skin Phototype Cutaneous reaction to UVR Australian Radiation Protection and Nuclear Safety Authority
(ARPANSA) together developed eye protection factor (EPF) number
I Always burns
ranges from 1 to 10 with respective to percent of blockage of sunrays.
Never tans Sunglasses labeled EPF of 9 or 10 transmit very little UV radiation. But
II Always burns easily choice of sunglasses should depend on individual visible quality and
Tans minimally which allows pupil to normal in light.
III Burns moderately Sunscreens: Sunscreens are cosmetic products to protect skin from
damage mediated by sunlight radiation.21 Topical sunscreen which either
Tans moderately
absorbs or reflects radiations to protect skin from harmful effects of
IV Burns minimally radiations unable to give complete sunscreen potential to organs like
Tans easily eyes, lips.22 While oral sunscreen products or constituents are also avail-
V Rarely burns able in market to be consume to avoid skin damage. Following are types
or classification23-24 of sunscreens:
Tans easily and substantially
VI Almost never burns Sunscreen Types on the basis of Mode of
Tans promptly and intensely application
very common options for sun protection but sunscreens are most pre-
Topical Organic 1. UVB filters
ferred and predominant mode of sun protection due to various societal
reasons like ease of application and higher efficacy of protection.17-18 PABA derivatives-Padimate O
Many animals (e.g. elephant uses mud as a physical barrier to block the Cinnamates-Octinoxate, Cinoxate
UV-rays and thus sunburns. Salicylates-Octisalate, Homosalate,
Trolamine salicylate
Sun protective clothing:19 Sun protective clothing are generally evalu-
ated on the basis of Clothing indices which is actually a UV protection Octocrylene, Ensulizole
factor (UPF) i.e the ratio of average effective UV radiation irradiance
transmitted and calculated through air to the average effective UV radia- 2. UVA filters
tion irradiance transmitted and calculated through fabric. Fabric UPF is Benzophenones (UVB and UVA2
similar to sunscreen SPF, except that during testing instead of sunscreen absorbers)-Oxybenzone, Sulisobenzone,
fabric is used to protect the skin. Such indices consider erythema as end- Dioxybenzone
point to determine how much longer a person can stay in the sun when Avobenzone or Parsol 1789 (UVA1
fabric covers the skin and expresses in form of following grades: absorber)
Meradimate (UVA2 absorber)
Grade UPF 3. Broad spectrum (UVA+UVB) filters-
good protection 15 to 24 Ecamsule (Mexoryl SX), Silatriazole
(Mexoryl XL), Bemotrizinol (Tinosorb S),
very good protection 25 to 39 Bisoctrizole (Tinosorb M)
excellent protection 40 to 50+ Inorganic agents function by reflecting,
Inorganic scattering or absorbing UV radiation..
Sun protective sunglasses: Sun protective sunglasses are only means
20
titanium dioxide (TiO2), kaolin, talc,
to protect delicate eyes from harmful effects of sun radiations. Their zinc oxide (ZnO), calcium carbonate, and
protection efficacy is generally evaluated on the basis of amount of light magnesium oxide
transmitted through a sunglass lens which is called as luminous trans- Natural Polyphones (tannins, flavonoids),
mittance. According to the Australian Standard (AS/NZS 1067:2003) chemicals lycopenes, fixed oils, volatile oils protects
sunglasses are classified as follows: skin from UV-induced free radical
generated damages by scavenging reactive
Luminous Category Class oxygen species
transmittance
Oral/Systemic Phenolics, flavonoids, tannins, carotenoids,
80-100% 0 Fashion spectacles: providing some or vitamins like chemicals on oral
no protection from UV radiation but no consumption exhibit antioxidant effect and
reduction in sunglare thus give photo protective action.
60-80% 1 Fashion spectacles: providing protection
from UV radiation and limited reduction
of sunglare-not suitable for driving at Sunscreen Regulations
night. Sunscreens are evaluated generally one of following method and fulfills
35-60% 2 Sunglasses for general use: provides labeling conditions as per countries guidelines.
medium protection from UV radiation and • US-FDA method: The FDA proposal measures in-vitro UV trans-
sunglare mittance through a sunscreen film using the critical wavelength
10-35% 3 Sunglasses: providing good protection method. Sunscreen products offering primarily UVB protection
from UV radiation and reduces sunglare would have a critical wavelength less than 320 nm, whereas those
3-10% 4 Sunglasses: providing a high level of UV providing both UVB and UVA protection would have critical wave-
radiation protection and reduced sunglare lengths between 320 and 400 nm. FDA requires that sunscreen
but must not be used when driving. products have a critical wavelength of at least 370 nm (the mean

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 DONGLIKAR AND SHARADA.: Synthetic and natural sunscreen

value must be equal to or greater than 370 nm) to be labeled as date from the Indian Drug and Cosmetic Act (1940) as amended
providing “broad spectrum” UVA and UVB protection.25 from time to time considers sunscreens as cosmetics. Bureau of
• UK method of boot star rating: The UK method, called as Boots Indian Standards (BIS), a participating member of the ISO, sets the
star rating system, also measures the UV transmittance through a relevant cosmetic product standards. Key points are stability data
sunscreen film. The substrate for measurement is abraded PMMA is (similar to Australia) must and there is no maximum SPF rating
plates. The ratio between the mean UVA and UVB absorbance for sunscreens.
measured before and after irradiation of the sunscreen products is • Japan: Japan Cosmetic Industry Association (JCIA) provides self
calculated.26 regulated standards. JCIA is a signatory to the COLIPA Interna-
• Australia: Australian standard (AS) method uses spectropho- tional SPF test method and JCIA has adopted ISO standards as they
tometer for measurements of the solar radiation transmitted by a are published. For SPF, ISO 24444 is accepted. In Japan, for UVA,
sunscreen product to yield a percentage of UVA radiation absorbed in-vivo testing is required and labelling is according to ratings of
by the product. According to this test, a product is designated as a Protection Grade of UVA (PA) i.e PA +, PA++ and PA +++. Addi-
long wave protector only if it transmits less than 10% of the incoming tionally, PA++++ was also added from 1st January 2013.
UV radiation between 320 and 360 nm. • China: Sunscreens are regulated under the Hygienic Standard for
• European countries: COLIPA is an association within the cosmetic Cosmetics 2007. Currently sunscreens can only be labeled up to
industry that voluntarily initiates the harmonization of labeling SPF 30+. The product must be labeled in Chinese language and
and product testing activities for sunscreen products. COLIPA have a Chinese name. Water resistance norms should be followed
guidelines are dedicated mainly to liquid and emulsion-type sun if lablled.
protection products. The test for UVA protection factors (UVAPF)
evaluation should be based on the assessment of UV transmittance Terminologies associated with Sunscreens30-34
through a thin film (0.75 mg/cm2) of the sunscreen sample spread • In-vivo sunburn protection factor (SPF): The Sun Protection
on a roughened substrate, before and after exposure to a controlled Factor can be defined, as proposed by the FDA in 1978, as the
dose of UV radiation from a strictly defined UV source. This numerical ratio between the minimal erythemal dose (MED) of
method allows in-vitro measurements of UVAPF values, which are sunscreen-protected skin, applied in the amount of 2 mg/cm2 and
shown to co-relate quite well with in-vivo results, determined with the Minimal Erythemal dose of unprotected skin, a mathematical
PPD method.27
relation that can be represented by the equation: SPF=MED (pro-
• International Organization for Standardization (ISO): It is an tected skin)/MED (unprotected skin)
independent, non-governmental international organization in
• In vitro Sunburn Protection Factor (SPF in vitro): The absolute
Geneva with a membership of 162 national standards bodies.28
protection performance of a suncare product against erythermal-
Following are different methods of ISO for sunscreens:
effective UV radiation, calculated from the measured in vitro trans-
• ISO 24443:2012 specifies an “in-vitro” procedure to characterize mittance and weighted with the erythema action spectrum and
the UVA protection of sunscreen products. Specifications are given with the “standard” output spectrum of a UV solar simulator used
to enable determination of the spectral absorbance characteristics for SPF testing.
of UVA protection in a reproducible manner. In order to determine
• In-vitro UVA protection factor (UVAPF): The absolute UVA
relevant UVA protection parameters, the method has been created
protection afforded by a suncare product, calculated from the
to provide a UV spectral absorbance curve from which a number
measured in-vitro transmittance after irradiation and weighted with
of calculations and evaluations can be undertaken. This method
relies on the use of in-vivo SPF results for scaling the UV absor- the PPD action spectrum and with the “standard” output spectrum
bance curve. of a UVA-filtered solar simulator.
• ISO 24442:2011 specifies an “in-vivo” method for assessment of • In-vitro UVA protection factor before UV exposure UVAPF:
the UVA protection factor (UVAPF) of topical sunscreen products. The in-vitro UVA protection factor measured before sample UV
It is applicable to cosmetics, drugs and other products intended to exposure. It is derived from the transmittance curve of the unex-
be topically applied to human skin, including any component able posed sample, weighted with the PPD action spectrum and with the
to absorb, reflect or scatter UV rays. ISO 24442:2011 provides a “standard” output spectrum of a UVA-filtered solar simulator, after
basis for the evaluation of sunscreen products for the protection of adjustment to the labeled SPF.
human skin against UVA radiation from solar or other light sources. • PFA (Protection Factor UVA) or UVA-PF (UVA Protection
• ISO 24444:2010 specifies a method for the in-vivo determination of Factor): The ratio of PPD of protected skin to PPD of unprotected
the sun protection factor (SPF) of sunscreen products. This Inter- skin.
national Standard is applicable to products that contain any com- • Critical Wavelength Value (λc): The critical wavelength λc value
ponent able to absorb, reflect or scatter ultraviolet (UV) rays and for the test product is defined as that wavelength where the area
which are intended to be placed in contact with human skin. ISO under the absorbance spectrum for the irradiated product
24444:2010 provides a basis for the evaluation of sunscreen products (obtained using the method described above) from 290 nm to λc
for the protection of human skin against “erythema” induced by solar is 90% of the integral of the absorbance spectrum from 290 nm to
ultraviolet rays. 400 nm.
In below mentioned countries Sunscreens are evaluated generally by one • UVA-UVB Ratio: Absorption of a 1.3 mg/square cm film is mea-
of above methods and fulfills labeling conditions as per countries guide- sured between 290 nm and 400 nm. The ratio of areas under the
lines.29 curve between 290-320 (UVB region) is compared with the area
• India: Indian being Asian population comes under Type–IV skin under the curve between 320 nm and 400 nm. Pre-irradiation of
pattern which burns minimally and tans easily. Freckles are rare but the sample is required. (Calculated as TPF x UVA/UVB). Various
still use of sunscreen is necessary to avoid tan. Indian regulations substrates can be nominated.

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 DONGLIKAR AND SHARADA.: Synthetic and natural sunscreen

• COLIPA (European Union): This technique involves measurement spectrum of a carefully prepared sample. There are two objectives in
of UVAPF/SPF Ratio and Critical Wavelength. UVA-PF shown a sample preparation method. The first is to simulate the application
to correlate quite well with in-vivo results, determined with PPD conditions used for in-vivo testing, both the applied quantity and sub-
method. strate interaction. This would produce a reliable in-vitro SPF value that
• Boots star rating system: The method used by Boots in the UK would positively predict the result of a subsequent in-vivo test. The
(not mandated). Absorption of a 1 mg/square cm film is measured second objective is for the method to be consistent enough to generate
between 290 nm and 400 nm. Pre irradiation of the sample is reproducible results sample-to-sample for the same sunscreen formulation.
required. Rating scale is 3 to 5 stars. More stars mean more protec- The spectral transmittance of a sunscreen in the ultraviolet spectral
tion (by ratio) in the UVA are as follows: range can be used to predict an in-vitro SPF value based on standard
erythema and solar data.32 The Boot’s Star and critical wavelength
Mean UVA/UVB ratio Star Rating Category methods for categorizing the effectiveness of UVA absorbers are also
0.0 to 0.59 No Rating performed from spectrophotometric data. Any pre-irradiation of samples
0.6 to 0.79 *** to evaluate their photostability, needs to be performed with a controlled
dose from a solar simulator. The flash lamp used in the UV-1000S does
0. 8 to 0.9 ****
not expose samples to excessive light doses, keeping the spectrophoto-
0.9 and over ***** metric analysis independent of any photostability issues.33 The recom-
• Immune protection factor (IPF): ability of sunscreen products to mended amount of sunscreen to apply in both FDA and COLIPA in-vivo
prevent UV-induced immune-suppression. IPF is assessed by com- methodologies is 2 mg/cm2 or 2 μL/cm2. Most sunscreens have a specific
plex methods such as the ability of a sunscreen to inhibit either the gravity of almost unity. The area of applicant on is measured and then
sensitization or elicitation arm of contact or delayed-type hypersen- the corresponding amount of sunscreen is measured using a pipette
sitivity reactions to allergens such as dinitrochlorobenzene (DNCB) (volume) or weighed by loss. The ideal substrate for in-vitro SPF needs
and nickel, respectively. IPF is considered to correlate better with to be fairly transparent to the ultraviolet and simulate the porosity and
the UVA-protectiveness of a sunscreen than with its SPF. texture of human skin, the in-vivo substrate. Suitable in-vitro substrates
• Broad spectrum sunscreen: Critical wavelength > 370 nm and range from human epidermis and mice epidermis to sausage casings
UVA protection factor > 4 and natural lamb condoms. Substrates that are commonly used are
Transpore, Vitro-Skin, Roughened Quartz Plate, polymethylmethacrylate
• Water-resistant sunscreen: Maintains the labeled SPF value after
(PMMA) plates, and PTFE (Teflon).34
two sequential immersions in water for 20 min (40 min)
• Very water-resistant sunscreen: Maintains the labeled SPF value
after four sequential immersions in water for 20 min (80 min) 1. In-vitro SPF determination (absorbance
measurement) by UV-Spectrophotometer35
Evaluation Methods Weigh 1 g of all samples, transfer to a 100 mL volumetric flask, dilute
In 1934, Friedrich Ellinger determined the minimal erythemal dose to volume with ethanol, followed by ultrasonication for 5 min and then
(MED) from protected and unprotected skin by evaluating the protective filter through cotton, rejecting the first ten mL. Transfer a 5.0 mL
efficacy of sunscreens using mercury lamp radiation on both forearms and aliquot to 50 mL volumetric flask and dilute to volume with ethanol.
expressed a coefficient of protection that decreased in value to the extent Then transfer a 5.0 mL aliquot to a 25 mL volumetric flask and complete
that protection increased. In 1956, Rudolf Schulze proposed “Schulze the volume with ethanol. Measure the absorptions of samples in solution
Factor” which been used for decades in European countries, as a reference in the range of 290 to 450 nm with every 5 nm increment using 1 cm
in the evaluation of sunscreens. Schulze Factor is exposure time required quartz cell, and ethanol as a blank. Calculate average of three determina-
for the induction of erythema on sunscreen protected and unprotected tions and calculate SPF by Mansur equation. EE* I values are constant
skin by incremental doses of sunlight like radiation emitted from lamps. and given in Table 1.
In 1974, Greiter introduced the term Sun Protection Factor (SPF) to
320
“Schulze factor.” From then till now SPF is popular term in evaluation SPFspectrophootometric  CF EE() I () Abs()
of sunscreens.35 In 1978, the North-American regulatory agency (FDA) 290

proposed the first normatization to determine the Sun Protection Factor

(SPF). Following are newly accepted and followed methods of evaluation Where: EE (I)–erythemal effect spectrum; I (l)–solar intensity spectrum;
of sunscreens: Abs (l)–absorbance of sunscreen product; CF-correction factor (=10).

In-vitro methods Table 1: Normalized product function used in

the calculation of SPF
Many regulatory agencies, such as the US Food and Drug Administration
(USFDA) and The European Cosmetic Toiletry and Perfumery Asso- Wavelength (λ) in nm EE x I (normalized)
ciation (COLIPA), mandate in-vivo testing on human subjects, using an 290 0.0150
erythemal endpoint to determine the SPF of a topical sunscreen. The 295 0.0817
in-vivo tests are costly and time-consuming and may not be practical
300 0.2874
for routine product evaluation. The UV-1000S is designed to make the
evaluation of SPF a simple and routine analytical procedure performed 305 0.3278
within the formulation laboratory.31 Although in-vivo testing is mandatory 310 0.1864
to make a product label claim for SPF, an investment in the UV-1000S 315 0.0839
will insure that only one in-vivo test will have to be performed for each 320 0.0180
particular formulation. The measurement of an in-vitro SPF can be
Total 1
performed by measuring the diffuse transmittance in the ultraviolet

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 DONGLIKAR AND SHARADA.: Synthetic and natural sunscreen

2. In-vitro Determination of SPF by UV 2000S UVA Ratio Star Category Descriptor

Ultraviolet Transmittance Analyzer (Labsphere) 0.0 to <0.2 Too low for UVA claim
The principle based on the sample transmittance measurement, where 0.2 to <0.4 Moderate
transmittance is defined as the ratio of the illumination passed through 0.4 to <0.6 ** Good
a sample to the illumination impaging on the sample. Procedure: Weigh
0.6 to <0.8 *** Superior
100 mg of the investigational sample and spread on the 56 cm2 area to
obtain a sample even film thickness of 2 µl/ cm2 on Transpore Tape as ≥0.8 **** Maximum
suggested in the operation manual of the UV-2000S Ultraviolet Transmit-
Another stipulation to using this method is to first evaluate the photo-
tance Analyzer for the sample preparation and application technique.33-34
stability of a sunscreen formula containing UVA absorbers. The samples
Expose the prepared sample to Xenon flash lamp for determining the Sun
must be pre-irradiated, using a solar simulator light source before the
Protection Factor as follows:
spectral transmittance is measured. The pre-irradiation exposure dosage
is measured in units of MED (minimal erythemal dose) and is equal

400
E S d to one third of the SPF value for the particular formulation under test.
SPF  290
The photostability concerns for certain sunscreen formulas support the

400
E S d
290 use of a flashlamp in the Labsphere UV-1000S. Pre-irradiating samples
Where, E (λ) is the erythema action spectrum, S(λ) is the solar spectral must be done with a continuous source whose spectrum and exposure
irradiance, T(λ) is the spectral transmittance of the sample with the inte- are closely monitored. The light source of the analyzing spectrophoto­
gral is calculate across the 290-400 nm wavelength limits. meter should not be used for sample irradiation. Broad Spectrum Rating
method relies only on the shape of the UV absorption spectrum and not
Critical wavelength method/Broad spectrum rating method United
on its amplitude. The problem of this test is quite small correlation with
States (FDA):33-34 Critical wavelength is the wavelength, at which 90%
in-vivo results.32-33
of the area under the extinction curve between 290 and 400 nm are
obtained or just a measure of the ‘breadth’ of UVA protection using a
test method called ‘critical wavelength’. The higher the extinction in the
In-vivo methods
UVA, the higher will become λc. This is proposed alternative to the Boots Following are commonly used in-vivo methods for SPF determination.
Star System. This evaluates the uniformity of a sunscreen product’s All three methods have somewhat similar procedure except their end-
absorbance spectrum. The result is based on a number called the critical points and expression of results. Procedure and endpoints are as follows:
wavelength which is determined spectrophotometrically from the absor- Procedure: Human volunteers are irradiated with a UVA light source
bance spectrum. The technique is not as sensitive to sample preparation (320÷400 nm) and skin changes, yielding in a immediate or persistent
as the in-vitro SPF or Boots Star measurements, since it only depends on pigment darkening or eryhema or tanning are observed after desired
the relative values of spectral absorbance and not the absolute values. In time following irradiation has been stopped.
this test proposal, the absorbance of the thin film of the sunscreen is inte- Observations: Within 60 sec after each exposure (IPD test), and again
grated (summed) from 290 nm across the UV wavelengths until the sum approximately 2 h after exposures (PPD test) and 16-24 h after exposures
reaches 90% of the total absorbance of the sunscreen in the ultraviolet (PFA), the irradiated sites were evaluated under bright “warm while”
region (290-400 nm). The wavelength at which the summed absorbance illumination (approximately 1000 Lux at 6000 K) for pigmentation re-
reaches 90% of total absorbance is defined as the ‘critical wavelength’ and sponse and erythema, using the following scales:
is considered to be a measure of the breadth of sunscreen protection.
Pigmentation Erythema
Filters are then classified as ‘broad spectrum’, having a significant part
of their absorbance in the UVA, when the critical wavelength is longer 0=No response 0=No response
than 370 nm. The critical wavelength is defined across the 290-400 nm 0.5=Equivocal response 0.5=Equivocal response
spectrums by the following equation: 1.0=Unambiguous dark grey or 1.0=Unambiguous erythema
brown pigmentation 1.5=Well defined erythema with
C  Min() 0.9    400

 290 A  1.5=Well define dark gray or sharp borders
290 A brown pigmentation with sharp
borders
2.0=Bright erythema

Where, A (λ) is the absorbance at wavelength λ and results of broad spec- 2.0=Deep pigmentation
trum rating method of United States should be predicted as follows:
• IPD (Immediate Pigment Darkening) by Kaidbey and Barnes:36
λc Level of Protection
where UVA protection factor from the ratio of the sunscreen
340 nm ≤ λχ<370 nm Some (UVA/UVB) protected minimal immediate pigment darkening dose to the
λc>370 nm More (broad-spectrum) un-protected minimal immediate pigment darkening dose within
60 sec after each exposure is determined. Endpoint for this method
UVA/UVB ratio: A recent concern with the SPF rating system for sun- is pigmentation producing a grade ≥1 within 1 min after each UVA
screens is that it is based on erythema as an endpoint. Therefore, active exposure.
ingredients that serve primarily as UVB blockers substantially improve • PPD (Persistent Pigment Darkening) by Chardon et al.:37 where
a product’s SPF. There is a need to add a product label system that UVA protection factor from the ratio of the sunscreen protected
describes the UVA protection offered in addition to the SPF. The spectral minimal immediate pigment darkening dose to the un-protected
transmittance values, Tλ, are converted to spectral absorbance values minimal persistent pigment darkening dose, evaluated approxi-
Aλ=-log (Tλ). A term called the UVA ratio is calculated as the ratio of mately 2 h after UVA exposure is determined. Endpoint for this
the total absorption in the UVA to that in the UVB.33-34 The star rating, method is pigmentation producing a grade ≥ 1, 2 h following UVA
and its associated claim for UVA protection, is determined as follows: exposure. The advantage of the PPD method, when comparing with

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 DONGLIKAR AND SHARADA.: Synthetic and natural sunscreen

IPD, is that the residual colour that has developed after exposure to Controversies45-46
the radiation is stabilized and allows more precise readings. Non-uniformity in SPF and related ratings of sunscreen products con-
• PFA (Protection factor in UVA) by Cole et al:38 where UVA fuses consumers. Sunscreens, particularly those with high SPF, may lead
protection factor from the ratio of the sunscreen protected minimal to a significant decrease in vitamin D production. Few of sunscreen
response dose (eryhema or tanning) to the unprotected minimal chemicals like cinnamates, PABA derivatives, benzophenones, and octo-
response dose, approximately 24 h after UVA exposures is deter- crylene observe to cause acute or chronic allergic symptoms. Vary small
mined. size inorganic filters found to have percutaneous absorption and endo-
• PPF (Phototoxic Protection Factor) by Lowe et al:33 where ratio of crine disrupting activity. Blockage of skin pores even causes acne and
sunscreen protected minimal phototoxic dose, measured 72 h after rosacea like adverse effects. Opaque nature and skin whitening effects
UVA exposure. This method uses 8-methoxypsoralen to increase are another inherent disadvantage of inorganic filters. Sunscreens cannot
sensitivity of UV-light. Endpoint for this method is erythema or be applied on cracked or wounded skin. Pediatric use of sunscreens is
tanning producing a grade ≥ 1 within 16-24 hr after UVA exposure. under study or with high precautions. Cost of sunscreen products always
inclines to higher side and hence year round regular use of sunscreens
Photo stability evaluation of sunscreens39 being expensive cannot be afforded by every population.
From study it is observed that after exposure to sunlight many sunscreen
chemicals undergo degradation and losses their photo protective prop- Natural chemicals as sunscreens
erties and thus efficacy of product. Hence it is must to determine photo Natural chemicals like polyphenols (flavonoids, tannins), carotenoids,
stability of sunscreens. Photo stability evaluation is done by measuring anthocyanidins, few vitamins, fixed oils, volatile oils from vegetables,
area under the curve index [AUCI] of sunscreens after either natural UV fruits, medicinal plant parts (leaves, flowers, fruits, berries), algae and
exposure (UVnat) or artificial UV exposure (UVart). Weigh 0.5 mg/cm2 lichens are more effective over synthetic chemicals which is due to their
of sunscreen and place between two plates of polished fused quartz silica long term beneficial effects especially against free radical generated skin
with diameter 25 mm and thickness 5 mm. Expose samples for 120 min damages along with UV-rays blocking.47-49 All of these possess strong
in outdoors especially in sunny weather as UVnat or use any artificial antioxidant activity. Most of them have moisturizing and cooling (aloe
sunlight radiation like lamp source as UVart. Measure absorption as vera juice, fixed oils), antimicrobial (volatile oils), wound healing and
follows: before exposure, after 30 min, 90 min and 120 min exposure of anti-inflammatory (polyphenols like curcumin), anticancer (tannins
natural or artificial UV sunlight. To eliminate the degradation possibi­ and resveratrol), anti ageing or cell rejuvenating (anthocyanidins, carot-
lity of the photoactive compounds by a temperature increase, try to heat enoids, vitamins) type of activities too.50-52 These all effects make them
plate for 20 min at constant temperature of sample upto 50°C ± 2°C on choice ingredients in cosmetics. Photo-radiation mediated skin damages
hot plate which is about 15°C higher than the temperature of the skin. require multiple protection means to produce long term benefits and
The spectra of prior to and after heating should be same if the photo­ avoidance of chronic conditions like cancers. Hence following natural
active chemicals do not undergo degradation. Calculate the AUC for chemicals47-55 use can be ideal in sunscreen products.
UVB (290-320 nm), UVA1 (340-400 nm), UVA2 (320-340 nm) for each
spectrum before [AUC before] and after [AUC after] before and after Consumer expectations
UVnat. The AUC Index (AUCI), defined as AUCI=AUCafter/AUCbefore. Consumers are in demand of all-in-one sunscreen product which should
If AUCI greater/equal to 0.80 then sunscreen is considered as photostable. be non-toxic, non-allergic, water or sweat proof, moisturizing, cooling,
antioxidant and UV-A as well as UV-B protective with high SPF values.56
Dosage and Application40-42 Skin radiating, anti-acne and anti-ageing sunscreens are also in demand.
It is found that sunscreen efficacy fails due to under application of In many sports, players spend their maximum time under sun and hence
defined dose or less practice of reapplication after simple wipe, sweating, better served with above mentioned improved products.
swimming and or vigorous activity. The dose used in FDA sunscreen
testing is 2 mg/cm2 of exposed skin. If one assumes an “average” adult Recent technology
build of height 5 ft 4 in (163 cm) and weight 150 lb (68 kg) with a 32-inch Sunscreens are more popular in the form of lotions, creams, gels, sprays,
(82-cm) waist, that adult wearing a bathing suit covering the groin area sticks and oils. Recently microsponges, microsphere, dendrimer,
should apply approximately 30 g (or 30 ml, approximately 1 oz) evenly liposome, nanoparticle incorporated more photo-stable and effective
to the uncovered body area. Larger or smaller individuals should scale sunscreens products are available in market. Sunscreens not remain a
these quantities accordingly. Considering only the face, this translates special cosmetic but many other photo-protective chemicals added
to about 1/4 to 1/3 of a teaspoon for the average adult face. Sunscreen cosmetics in hair care (e.g. shampoo), skin care (e.g. moisturisers, foun-
should be applied properly in a concentration of 2 mg/cm2 to all sun dations and concealers), lip care (e.g. lipsticks, lip balms) and even in eye
exposed areas and allowed to dry completely before sun exposure. care (e.g. eye creams) with more than 30 SPF are available in market.57-58
It should be reapplied every 2 h, and after sweating, swimming, vigorous
activity or exercise and or after each wipe. CONCLUSION
Thus it can be concluded that there is great market potential for sunscreen
Labeling43-44 chemicals either synthetic or natural or in combination due to awareness
The critical wavelength of a sunscreen needs to be equal to or higher of protection from hazardous UVA as well as UVB rays. Photo-stable,
than 370 nm in order to claim “broad spectrum,” and only “broad uniform UVA/UVB protective sunscreen product with high SPF can
spectrum” sunscreens with an SPF equal to or higher than 15 can claim be minimum ideal requirement but natural chemicals like polyphenols
benefits against skin cancer and skin aging as directed in the monograph. (flavonoids, tannins), carotenoids, anthocyanidins, few vitamins, fixed
Sunscreens previously qualified as water resistant now labeled as “water oils and volatile oils from vegetables, fruits, medicinal plant parts (leaves,
resistant (40 min).” Those previously qualified as very water resistant flowers, fruits, berries), algae and lichens are more effective due to their
now labeled as “water resistant (80 min).” Terms such as “waterproof,” long term beneficial effects especially against free radical generated skin
“sweatproof,” and “sunblock” not allowed and prohibition ARE enforced. damages along with UV-rays blocking. These natural chemicals incor-

176 Pharmacognosy Journal, Vol 8, Issue 3, May-Jun, 2016

 DONGLIKAR AND SHARADA.: Synthetic and natural sunscreen

Class Sources Mode of action of photo protection

Flavonoids
Cereal grains and aromatic herbs (parsley,
Apigenin (5,7,4’-trihydroxyflavone) is a widely Inhibits UV mediated induction of ornithine
rosemary, thyme), fruits (apples, cherries, grapes),
distributed plant flavone decarboxylase activity, down-regulates COX-2
vegetables (beans, broccoli, celery, leeks, onions,
expression in macrophages
barley, tomatoes) and beverages (tea, wine)
Chrysin (5,7-dihydroxyflavone), an analog of
apigenin, is a natural flavone Propolis and honey Inhibits UV mediated induction of ROS

Fruits and vegetables (apples, grapes, lemons, Protects skin’s antioxidant systems (glutathione
tomatoes, onions, lettuce, broccoli, kale, peroxidase, glutathione reductase, catalase and
Quercetin (3,5,7,3’,4’-pentahydroxyflavone, is one cottonseed etc.), beverages (tea, red wine), herbs superoxide dismutase activities), prevention of
of the most potent antioxidant compounds (Gingko biloba, Apocynum venetum, Poacynum UVC radiation-induced liposome peroxidation
hendersonii, Opuntia ficusindica) , olive oil, and SPF of quercetin matches to homosalate, a
propolis from bee hives. synthetic sunscreen agent
Silymarin is a standardized extract of flavonolignan
diastereoisomers silibinin A and silibinin B in a Inhibition of UVB-induced oxidative stress,
Seeds of the milk thistle
roughly 1:1 ratio, the diastereoisomers isosilibinin inflammation and suppression of immune system
A and isosilibinin B, silicristin, and silidianin
Through enhancement of antioxidant enzyme
activities and scavenging of oxygen free radicals,
Genistein (4’,5,7-trihydroxyisoflavone, Soybean isoflavone
specific inhibitor of protein tyrosine kinase, and
phytoestrogen
Byproduct of soybean (Glycine max L) oil Able to inhibit UVB induced keratinocyte death,
Isoflavones like daidzein, genistein, and glycitein processing and also present in Red clover (Trifolium release of hydrogen peroxide (H2O2), and UVB
pratense L.) induced MAPK phosphorylation
Tannins
Catechins including (−) epicatechin (EC), (−) Reduces DNA damage and erythema formation
epicatechin-3-gallate (ECG), (−) epigallocatechin due to protection of DNA repair enzymes from
Green tea, pomegranate, Amla,
(EGC), (−) epigallocatechin-3-gallate (EGCG), (+) inactivation by ROS and due to UVB absorption
catechin, and (+) gallocatechin (GC) ability of green tea polyphenolic
Anthocyanidins
Inhibits the adverse effects of UVB exposure
including translocation of transcription factors
Colored (range from yellow to purple (except
NF-kB and AP-1, over expression of the
Anthocyanidins mixtures green) fruits, flowers and berries, vegetables, cereal
pro-inflammatory cytokine IL-8, cleavage of
grains, (e.g. Pomegranate (Punica granatum)
procaspase-3 (a key step in apoptotic pathway),
and DNA fragmentation
Protects skin via transcriptional mechanisms of
Cyanidin 3-glycosides Citrus species
NF-κB and MAPK signaling
Blocks collagen destruction and inflammatory
Pelargonidin Strawberries and other berries responses via transcriptional mechanisms of NF-
κB and MAPK signaling
Carotenoids
Tomatoes (Solanum Lycopersicum), Carrots
β-carotene, As a chain breaking antioxidant in a lipid
(Daucus carota) and in many red-orange colored
lycopenes peroxidation.
fruits and vegetables
As a chain breaking antioxidant in a lipid
Fucoxanthin, astaxanthin Brown algae
peroxidation.
Other poly-phenoilc compounds
Grape ( Vitis vinifera) Inhibits ODC and COX-2 activity. Inhibit increased
Resveratrol (Trans-3’4’5’-trihydroxystilbine)
Nuts, fruits level of lipid peroxidation
Scavenge ROS, by interrupting the activation of
protein kinase-C. Enhance glutathione content
Curcumin Roots of Curcuma longa Zingiberaceace and GST activity. Inhibit lipid peroxidation and
arachidonic acid. Inhibit Ornithin decarboxylase
(ODC) activity

Continued.....

Pharmacognosy Journal, Vol 8, Issue 3, May-Jun, 2016 177

 DONGLIKAR AND SHARADA.: Synthetic and natural sunscreen

Class Sources Mode of action of photo protection

Vegetables, Olive oil (Olea europoea) Oleaceae, Inhibits formation of hydroxyl radicals, scavenges
Caffeic, coumaric, cinnamic and ferulic acids
caper (Capparis spinosa), both hydroxyl and superoxide radicals.
Stigmas of crocus flowers (Crocus sativus) crocin-
(responsible for the color), picrocrocin-(responsible Ameliorates antioxidant enzymes and suppresses
Saffron
for the bitter taste), and safranal-(responsible for lipid peroxidation and nitric oxide formation
odor and aroma)
Usnic acid, 1-chloropannarine, epiphorelic acid I As a chain breaking antioxidant in a lipid
Lichens (symbiotic organisms of fungi and algae)
and II, calicin, depsides, and depsidones peroxidation.
Phlorotannins and dieckol, Plastoquinones, As a chain breaking antioxidant in a lipid
Green red alga
sargaquinoic acid, and sargachromenol peroxidation.
Vitamins
Vitamin C Most fruits and vegetables ( amla, papaya, orange, Inhibits solar radiation induced p53 powerful
(Ascorbic acid) lemon, grapes, tomatoes, mango) antioxidant enhancer.
Vitamin E Interrupts free radical chain reactions by capturing
Green leafy vegetables and fortified cereals
(Tocopherol) the free radical
Shea butter, Jojoba oil, Olive oil, Coconut oil, Castor oil, Almond oil, Mustard oil, Chaulmoogra oil,
Fatty oils
Sesame oil
Peppermint oil, Tulsi oil, Lemon grass oil, Lavender oil, Orange oil, Lemon oil, Eucalyptus oil, Tea-tree oil,
Volatile oils
Rose oil

porated sunscreens might provide cost effective, truly broad spectrum 11. Berwick M, Pestak C, Thomas N. Solar ultraviolet exposure and mortality from
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sunscreen products with antioxidant, wound healing, anti-inflammatory
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and many more skin protective effects. 277-90.
13. Amaro-Ortiz A, Yan B, D’Orazio JA. Ultraviolet radiation, aging and the
ACKNOWLEDGEMENT skin: prevention of damage by topical CAMP manipulation. Molecules.
2014:5;19(5):6202-19.
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VI. Arch Dermatol. 1988;124(6):869-71.
Authors do not have conflict of interest. 16. Gies PH, Roy CR, Toomey S, McLennan A. Protection against solar ultraviolet
radiation. Mutation Research. 1998;422(1):15-22.
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PICTORIAL ABSTRACT SUMMARY

• Over exposure to sunlight causes number of skin problems.
• There is rise in sunscreen demand all over the world.
• Sunburn protection factor (SPF) is measurable output to calculate efficacy
of sunscreens.
• In vitro determination of SPF is capable to predict in-vivo efficacy of sun-
screens.
• Labeling conditions are different for different regions of world.
• Natural photoprotective chemicals along with antioxidants can provide
broad spectrum protection.
• Natural antioxidant chemicals possesses additional antiageing, anti-in-
flammatory and many more protective effects.
• Consumer demand is of all-in-one sunscreen product.

ABOUT AUTHOR
Dr. S. L Deore: Has completed her B. Pharm from A. R.A. College of Pharmacy, Dhule, and Maharashtra. She is GOLD MEDALIST in [Link]
from North Maharashtra University in 2004. She has qualified GATE in 2004 with 90 %. She has completed [Link] from Govt. College of phar-
macy, Amravati in 2006. She has awarded PhD in pharmaceutical sciences by SGB Amravati University in May 2011. She has isolated saponins in
her PhD work. She has published 35 research papers in various national- international journals about the medicinal plants and herbal drugs. She
has presented 25 posters in various national and international conferences. She has published 02 reference books. She has authored Textbook of
Pharmacognosy and Phytochemistry, PharmaMed Press, Hyderabad. Her books are included in pharmacy syllabus of Pune, Jalgaon, kerala and
JNTU University. She has organized 03 national workshops and 02 state level seminars in her institute. She has been awarded with “Young scientist
award” as recognition of devotion and interest on Medicinal plants and Herbal products at the International Level in 2nd International Seminar on
Medicinal Plants and Herbal Products. She has guided 22 [Link] students and 03 Ph.D research are going under her guidance. Presently she is
working with Govt. College of Pharmacy, Amravati (Maharashtra) as an Assistant professor where she has selected through MPSC. She has filed
04 Indian patents on phytochemicals. She has fetched Research Promotion Grant (RPS) of 11.5 L from AICTE, Delhi for production of Plant antibod-
ies. She has also been awarded with Career award for Young teachers by AICTE. Her areas of research are isolation and structural elucidation of
phytochemicals, intellectual property rights, neutraceutical development, and traditional medicine screening, chromatographic and phytochemical
analysis of extracts.

Pharmacognosy Journal, Vol 8, Issue 3, May-Jun, 2016 179

Research Article ISSN 2690-537X

Research Article Dermatology Research

Sunscreens’ Percutaneous Absorption and Ingredients Concentration in

Human Plasma and Urine: A Systematic Review
Farnoosh Seirafianpour1#, Navid Sadeghi Azad2#, Atefeh Naeimifar3, Milad Dodangeh1, Masoud
Pourghahramani koltapeh1, Sepideh Safari4, Howard Maibach5, Seyed Sajad Alenabi6, Parsa Panahi1,
Bita Mehravi7* and Shohreh Nafisi8*
Co-First Authors.
#

1
Student Research Committee, school of medicine, Iran University
of Medical Sciences (IUMS), Tehran, Iran.
2
Department of Medical Nanotechnology, Faculty of Advanced
Technologies in Medicine, Iran University of Medical Sciences,
Tehran, Iran.
*
Correspondence:
Department of Pharmaceutics, Faculty of Pharmacy, Tehran
3 Shohreh Nafisi, Department of Chemistry, IAUCTB, 14169
University of Medical Sciences, Tehran, Iran. 63316 Tehran, Iran, Department of Dermatology, University of
California, San Francisco, CA, USA.
4
Razi Drug Research Center, Iran University of Medical Sciences,
Tehran, Iran.
Bita Mehravi, Department of Medical Nanotechnology, Faculty
5
Department of Dermatology, University of California, San of Advanced Technologies in Medicine, Iran University of
Francisco, CA, 94115, USA. Medical Sciences, Tehran, Iran.
Faculty of Pharmacy, Mazandaran University of Medical Sciences,
6

Mazandaran, Iran. Received: 30 Jun 2022; Accepted: 02 Aug 2022; Published: 07 Aug 2022
7
Department of Medical Nanotechnology, Faculty of Advanced
Technologies in Medicine, Iran University of Medical Sciences,
Tehran, Iran.
8
Department of Chemistry, IAUCTB, 14169 63316 Tehran,
Iran, Department of Dermatology, University of California, San
Francisco, CA, USA.

Citation: Farnoosh Seirafianpour, Navid Sadeghi Azad, Naeimifar A, et al. Sunscreens’ Percutaneous Absorption and Ingredients
Concentration in Human Plasma and Urine: A Systematic Review. Dermatol Res. 2022; 4(1): 1-13.

ABSTRACT
Sunscreen application is widespread and incorporated into daily life. Although FDA has approved 16 sunscreen
ingredients, recent studies suggest a revaluation of their potential adverse effects. This systematic review assesses
sunscreens’ percutaneous absorption, toxicity, and their ingredients concentration in urine and plasma. The search
was conducted in Medline (PubMed), Scopus, Embase, and Cochrane until 05/08/2021. Data from 21 studies with
related inclusion criteria were extracted. 18 studies reported sunscreen complications such as rash, irritation,
immune system disorders, stratum corneum DNA damage, and hormonal disruption, 4 articles reported maximum
concentration of sunscreen ingredients in plasma, and 4 articles reported urinary concentration of ingredients. In
2016, the FDA suggested a plasma concern level of 0.5 ng/mL for sunscreen ingredients. Sunscreen ingredients
including avobenzone, octocrylene, ecamsule, homosalate, octisalate, enzacamene, octinoxate, and oxybenzone
were detected more than 0.5 ng/mL after in blood 1-4 daily applications. Sunscreen application reduces the risk
of sunlight harmful effects but could have advers effects related to their percutaneous penetration. Taken together,
related data provide the impetus for detailed analysis of sunscreen toxicology. Also, highly adsorbed ingredients
should be replaced with less adsorbed compounds to minimize body accumulation and the associated risks. Also,
life time infant and children sunscreen exposure provide furthur impetus for in-depth toxicologic investigations.

Dermatol Res, 2022 Volume 4 | Issue 1 | 1 of 13

Keywords
Sunscreen, Sun protection, Sunscreens adverse effect, Sunscreens In-vivo research studies on BP-3 effect on children's birth weight
ingredient, Percutaneous penetration, Plasma concentration, Urine and gestational age [27] raised concerns about sunscreen’s
concentration. hormonal effects [28]. BP-3 also indicated proliferative effects on
MCF-7 breast cancer cells [28]. BP-3 cytotoxicity may be caused
Abbreviations by oxidative stress relevant to high Zn2+ intracellular levels [29].
SPF: Sun Protection Factor, UVR: Ultraviolet Radiation, GRASE:
Generally Recognized as Safe and Effective, MPPD: Minimal Objective
Persistent Pigment Darkening, MED: Minimal Erythema Dose. This review evaluates sunscreens complications in human, clinical
trials, their absorption and urinary, plasma concentration after
Introduction application. Intended PICO in our study are as follows; population:
Sunscreen products especially those designed for human sun all people who use sunscreen (any age or race), intervention: use of
protection are available in the market as creams, gels, lotions, oils, sunscreen (any form), comparison: no use of sunscreen, outcome:
sticks, and sprays [1] and are classified as over-the-counter drugs urinary concentration, plasma concentration, or complication.
in the USA. The first use of primary synthetic sunscreens was in
1928 and the first major commercial product was marketed in 1936 Method
[2]. Approximately, one-third of adults usually or always utilize Protocol and registration
sunscreens when in the sun: 14% of males and 29% of females in We followed the PRISMA (Preferred Reporting Items for
the US use sunscreen regularly on their faces and other body parts Systematic Reviews and Meta-Analyses) guidelines [30].
[3]. Sunscreens are divided into physical and chemical sunscreens
[4]. Physical sunscreens such as titanium dioxide and zinc oxide Eligibility Criteria
function by scattering, reflecting or blocking UVA, UVB, and Inclusion criteria included English studies on the use of sunscreen
UVC radiations [5]. Most Sunscreens contain organic compounds in the human population and examination of the concentration of
such as aminobenzoic acid, avobenzone, cinoxate, dioxybenzone, sunscreen ingredients in the blood or urine, or the side effects after
ensulizole, homosalate, menthyl anthranilate, mexoryl S.X., sunscreen application. Exclusion criteria were review articles,
octocrylene, octyl methoxycinnamate, octyl salicylate, case reports, in-vitro studies, and studies that not met the inclusion
oxybenzone, padimate O, phenyl benzimidazole, sulisobenzone, criteria.
and trolamine salicylate which act by absorbing UV radiation and
scattering solar energy [6-9]. Recently, sunscreens consumption Databases
has increased and starts from 6 months of age [10]. The search was performed on PubMed (http:/[Link] /
pubmed), Scopus
Repeated long-term UVR contact leads to skin aging and increasing (http:/[Link]), Embase (http:/[Link])
skin cancer risk [11]. UVB affects DNA damage, epidermis and Cochrane
hyperplasia, and skin inflammation [12]. Skin cancer is the most (https:/[Link]/) up to 05/08/2021, and all
common cancer [13]. Almost 5 million new skin cancer cases are articles on sunscreen use in humans were studied.
reported annually in the US, comprising approximately 90,000
melanomas, the deadliest skin cancer. Sunscreen’s actives used Search strategy
in personal care and cosmetics can absorb UVA (320–400 nm) Table 2, the ‘supplement file’, shows that the search was
and UVB (290–320 nm) photons energies [14,15]. FDA-approved started and completed on 05/08/2021. Sunscreen agents, sun
sunscreens is provided in ‘supplement file’ (Table 1). protection factor, sunscreen application and synonyms, toxicity,
adverse effects, complications and synonyms, percutaneous
Recently, reports regarding sunscreens’ adverse effects have absorption, percutaneous permeation, plasma concentration, urine
increased; around 12% of users report irritation [10-16]. Recently, concentration, circulation, and synonyms were the key search
concern of potentil internal organ effects has increased. Systemic words. Search was not limited to the publication year, language,
exposure has been observed in in-vitro and in-vivo studies [16- region, race, or any other conditions.
22]. FDA proposed a steady-state concentration of 0.5 ng/ml in
the bloodstream for the sunscreens’ active ingredients as a safety Study selection
threshold [23]. A total of 3148 studies were included, 869 articles were duplicates
and removed, and 2279 articles were screened by reviewers;
Benzophenone-3 (BP-3) concentration in the bloodstream by FDA articles were screened by two independent reviewers, and 358
is up to 6% [24,25]. The results of a study on 25 volunteers who articles remained after the title-abstract screening and evaluated in
applied a sunscreen containing 4% BP-3, twice daily, for 5 days, full text, stated in detail in PRISMA flow chart shown in Figure 1.
indicated that there was accumulation in the amount excreted with Finally, 21 articles met inclusion criteria, and reviewers extracted
repeat administration and that 1.2-8.7% (mean 3.7%) of the total the results. We selected studies which documented sunscreens
amount of BZ-3 applied was excreted in urine [26]. usage complications, sunscreens ingredients concentration in

Dermatol Res, 2022 Volume 4 | Issue 1 | 2 of 13

Table 1: Sunscreen Data from Articles That Reported Plasma Concentration.
population sunscreen

Follow up duration
Use in
Octyl
Oxybenzone or which parts How many
Sex ratio Enzacamene OR methoxycinnamate Amount How
First author
Country Population

Age (mean)
Avobenzone OR Butyl benzophenone-3 Octocrylene of the body times
(Percentage Type Ecamsule 3-(4-methylbenzylidene) or ethylhexyl used (mg/ many days
No. methoxydibenzoylmethane or BP-3 OR (OCT) (percentage application per
of female) camphor (4-MBC) methoxycinnamate or cm2) application

(days)
BZP-3 from whole day
Num.
Year

octinoxate (OMC)
body)
Once on day 1
Matta MK

United and 4 times per

1 12 50% 21 lotion 3% 4% 6% Nm Nm Nm 2 mg/cm2 75% 4
States day for day 2,
2020

45.1
3, and 4
Once on day 1
Matta MK

United Aerosol and 4 times per

2 12 50% 21 3% 6% 10% Nm Nm Nm 2 mg/cm2 75% 4
States Spray day for day 2,
2020

41.4

3, and 4
Once on day 1
Matta MK

Non-
United and 4 times per
3 12 50% 21 aerosol 3% Nm 10% Nm Nm 7.5% 2 mg/cm2 75% 4
States day for day 2,
2020

39.2

Spray
3, and 4
Once on day 1
Matta MK

United Pump and 4 times per

4 12 50% 21 3% Nm Nm Nm Nm 7.5% 2 mg/cm2 75% 4
States Spray day for day 2,
2020

3, and 4
29
Matta MK

United
5 6 50% 7 spray 3% 6% 2/35% 0 0 0 2 mg/cm2 75% 4 4
States
2019

42/5
Matta MK

United
6 6 50% 7 spray 3% 5% 10% 0 0 0 2 mg/cm2 75% 4 4
States
2019

33/7
Matta MK

United
7 6 50% 7 lotion 3% 4% 6% 0 0 0 2 mg/cm2 75% 4 4
States
2019

34/5
Matta MK

United
8 6 50% 7 cream 2% 0% 10% 2% 0 0 2 mg/cm2 75% 4 4
States
2019

31/7
Julia Hiller

9 Germany 20 50% 6 lotion YES 0 YES 0 0 0 2 mg/cm2 Nm NM 4

2019

24/5
Julia Hiller

10 Germany 20 50% 6 lotion YES 0 YES 0 0 0 2 mg/cm2 Nm NM 4

2019

24/5
NR Janjua

11 Denmark 17 100% 14 cream 0 10% 0 0 10% 10% 2 mg/cm2 100% 4 1

2007

65
NR Janjua

12 Denmark 15 0% 14 cream 0 10% 0 0 10% 10% 2 mg/cm2 100% 4 1

2007

26

Dermatol Res, 2022 Volume 4 | Issue 1 | 3 of 13

Table 2: Maximum concentration of sunscreen active ingredients observed in human plasma across
Maximum plasma concentrations
4-methylbenzylidene
Octymethoxycinnamate
Avobenzone Oxybenzone Octoclylene Ecamsule
camphor(omc)
Mean Mean or
Coefficient of Min (ng/ Max (ng/ Mean (ng/ Coefficient of Min (ng/ Max (ng/ Mean (ng/ Coefficient of Min (ng/ Max (ng/ Mean (ng/ Coefficient of Min (ng/ Max (ng/ Mean (ng/ Max (ng/ Max (ng/
Num.

(ng/ median
Variation% ml) ml) ml) Variation% ml) ml) ml) Variation% ml) ml) ml) Variation% ml) ml) ml) ml) ml)
ml) (ng/ml)
1 7.1 73.9 2.9 28 28.1 53.0 131.3 498.1 7.8 87.1 2.6 38.7 Nm Nm Nm Nm Nm Nm NM NM
2 3.9 70.9 1 9 180.1 57.3 70.1 476.9 6.6 78.1 1.4 16.2 Nm Nm Nm Nm Nm Nm NM NM
3 3.5 73.0 1 10 Nm Nm Nm Nm 6.6 103.9 1.7 34.4 Nm Nm Nm Nm Nm Nm 7.9 30.6
4 3.3 47.8 1.2 6.2 Nm Nm Nm Nm NM NM NM NM Nm Nm Nm Nm Nm Nm 5.2 11.8
5 4 60/9 1/6 8/3 209/6 66/8 83/3 532 2/9 102 1 9/8 Nm Nm Nm Nm Nm Nm Nm Nm
6 3/4 77/3 1 7/3 194/9 52/4 89/3 350/1 7/8 113/3 2/5 20/4 Nm Nm Nm Nm Nm Nm Nm Nm
7 4/3 46/1 2/8 9/3 169/3 44/5 103/3 274/6 5/7 66/3 2/8 13/4 Nm Nm Nm Nm Nm Nm Nm Nm
8 1/8 32/1 1/1 2/7 Nm Nm Nm Nm 5/7 47/1 2/9 10/3 1/5 166/1 0/5 12/1 Nm Nm Nm Nm
9 4 Nm Nm 11/3 Nm Nm Nm Nm Nm Nm Nm Nm Nm Nm Nm Nm Nm Nm Nm Nm
10 Nm Nm Nm Nm Nm Nm Nm Nm 11/7 Nm Nm 25 Nm Nm Nm Nm Nm Nm Nm Nm
11 Nm Nm Nm Nm 187 Nm Nm 200 Nm Nm Nm Nm Nm Nm Nm Nm 16 20 7 10
12 Nm Nm Nm Nm 238 Nm Nm 300 Nm Nm Nm Nm Nm Nm Nm Nm 18 20 16 20

Table 3; sunscreen ingredients in articles that reported urine sample

Population Sunscreen ingredient

or trisodium edta
Octyl salicylate*6

Silicon dioxide*7

Dioxybenzone*9
sunscreen users

Ethylhexylglyc-
Dimethicone*10
Enzacamene*4

vp/hexadecene
Oxybenzone*2

Tocopherol*11
Avobenzone*1

disodium edta
Octocrylene*3

Citronellol*13
Coumarin*12
Octinoxate*5

Propylheptyl
Julia hiller First author

salicylate*14
(percentage
Age (mean)

Acrylates*8

Linalool*15
Number of

hydroxide
Panthenol
copolymer
of female)

Titanium

caprylate
Sex ratio
Country

Sodium
dioxide

Benzyl

erin*16
Type
Year

Germany

50% yes yes yes yes yes yes yes yes yes yes yes yes yes yes yes yes yes yes yes
lotion
2019

24/5
20
Julia hiller

Germany

50% yes yes yes yes yes yes yes yes yes yes yes yes yes yes yes yes yes yes yes
lotion
2019

24/5
20
Denmark
nr janjua

100% yes yes yes

cream
2007

17

65
Denmark
nr janjua

0% yes yes yes

cream
2004

15

26
gonzalez, h.
gustavsson

36% yes
Sweden

lotion
2002

11

26

1
* avobenzone or butyl methoxy dibenzoyl methane 6
* octyl salicylate, or 2-ethylhexyl salicylate or butyloctyl salicylate or 11
* tocopheryl acetate or tocopherol or vit e acetat
2
* oxybenzone or benzophenone-3 or bp-3 or bzp-3 ethylhexyl salicylate 12
* coumarin or 2h-chromen-2-one
3
* octocrylene or oct
7*
hydrated silica or silicon dioxide
13
* citronellol or dihydrogeraniol
8
* c12-22 alkyl methacrylene copolymer or c10-30 alkyl acrylate or acrylates
14
* benzyl salicylate or salicylic acid benzyl ester
4
* enzacamene or 3-(4-methylbenzylidene) camphor (4-mbc) 15
* terpene alcohol or linalool
5
* octyl methoxycinnamate or ethylhexyl methoxycinnamate or octinoxate (omc)
9
* c12-15 alkyl benzoate or dioxybenzone 16
* ethylhexylglycerin, or octoxyglycerin, or glyceryl ether
10
* dimethicone or polydimethylsiloxane, stearoxy dimethicone

Dermatol Res, 2022 Volume 4 | Issue 1 | 4 of 13

Table 4: sunscreen ingredients in urine samples according to studies which shows the high absorption of these substances
urine concentration
Octyl methoxycinnamate
Enzacamene OR
Use in which How How or ethylhexyl
First author The amount Follow up Avobenzone Benzophenone-3 3-(4-methylbenzylidene)
methoxycinnamate or
Octocrylene (OCT)
parts of many many camphor 4-mbc
used (mg/ duration octinoxate (omc)
the body days times a
cm^2) (days)
(percentage) use day mean mean
min max percentage min max mean min max mean min max mean min max
(ng/ml) (ng/ml)
Tatsuya kunisue Not report 6%
Julia hiller 2 4 6 1/7 1/5 1/9
Julia hiller 2 4 6 7/9 6/9 8/9
Nr janjua 2 100% 4 1 14 44 60 4 5 6 5
Nr Janjua 2 100% 4 1 14 81 140 4 7 4 8
Gustavsson Gonzalez 4 100% 2 5% 9/8 11

Table 5: characteristics of articles that reported adverse effects

Population Sunscreen
Year Num. First author Country Population number Sex ratio
Age (mean) Type
Sunscreen Users Control group percentage of female
2020 1 Matta MK United States 12 0 45.1 50% Lotion
2020 2 Matta MK United States 12 0 41.4 50% Aerosol Spray
2020 3 Matta MK United States 12 0 39.2 50% Nonaerosal Spray
2020 4 Matta MK United States 12 0 29 50% Pump Spray
2019 5 Matta MK United States 6 0 42/5 50% spray
2019 6 Matta MK United States 6 0 33/7 50% spray
2019 7 Matta MK United States 6 0 34/5 50% lotion
2019 8 Matta MK United States 6 0 31/7 50% cream
2019 9 Lindstrom, A. R. Nambour 812 809 Nm 44% Nm
2014 10 Katie Beleznay Canada 23 0 41/5 100% Nm
2009 11 ALASTAIR C. KERR France 94 0 44 Nm Nm
2010 12 Numano, K. Japan 41 0 7/8 Nm Nm
1987 13 English, J. S. C. United Kingdom 280 0 Nm Nm Nm
2003 14 Choi, J. South Korea 200 0 Nm Nm ointment
2017 15 Anežka Sharma Nm 2 2 28 100% lotion
2015 16 Boonchai, W. Thailand 30 0 34/1 93/30% cream
1998 17 Berne, B. Sweden 355 0 43/9 69% Nm
1998 18 Berne, B. Sweden 355 0 43/9 69% Nm
1998 19 Berne, B. Sweden 355 0 43/9 69% Nm
1998 20 Berne, B. Sweden 355 0 43/9 69% Nm
1998 21 J. FARRERONS spain 24 19 71 58% cream
2016 22 Jorge Aburto-Corona, USA 10 10 22/3 50% Nm
2016 23 Jorge Aburto-Corona, USA 10 10 22/3 50% Nm
2012 24 A. Faurschou Denmark Nm 10 Nm 54% Nm
2012 25 A. Faurschou Denmark 7 Nm Nm 54% Nm
2012 26 A. Faurschou Denmark 7 Nm Nm 54% Nm
2012 27 A. Faurschou Denmark 7 Nm Nm 54% Nm
2012 28 A. Faurschou Denmark 6 Nm Nm 54% Nm
2007 29 NR Janjua Denmark 32 32 Nm 53% cream
2004 30 NR Janjua Denmark 32 32 65 53% cream
1997 31 Hayag, M. V. USA 9 9 40 33% Nm
1995 32 marks.r Australia 113 113 Nm Nm Nm

Dermatol Res, 2022 Volume 4 | Issue 1 | 5 of 13

Table 6: Sunscreen’s adverse effect
Complications

Use in which parts

The amount used

How many times

How many days
Rash Irritation Deaths Cardiovascular disease deaths Cancer deaths

duration (days)
Significant
Decrease
Immune DNA Hindered

of the body
(mg/cm^2)
Hormonal 25-hydroxy

Follow up
percentage percentage percentage
percentage hazard percentage percentage hazard hazard system damage disruption vitamin D
effective
percentage percentage in case in case in control
in control ratio in case in control ratio ratio disorder in stratum sweating
Num.

a day
levels
SPF

group group group

use
corneum
1 2 75% 4 4 21 8.3% 8.3%
2 2 75% 4 4 21 50% 0
3 2 75% 4 4 21 42% 0
4 2 75% 4 4 21 17% 0
5 2 75% 4 4 7 17%
6 2 75% 4 4 7 17%
7 2 75% 4 4 7 17%
8 2 75% 4 4 7 17%
9 27% 1460 1 7665 20% 21% 0/94 7% 9% 0/77 8% 7% 1/09
10 patch 9% 2 1 5 17/39%
11 patch 9% 2 1 5%
12 99% 28 0/43 0%
Patch
13 4 1 5%
test
14 1 4%
15 26/4 9% 1 3 0/33 yes yes yes yes
16 60 5% 90 90 30%
17 patch 2 1 3 4/22%
18 patch 2 1 3 3/38%
19 patch 2 1 3 1/70%
20 patch 2 1 3 0/56%
21 15 27% 730 1 yes
22 50 1 9%
23 50 1 9% yes
24 8 25% 3 yes
25 8 0/5 25% 3 yes
26 8 1 25% 3 yes
27 8 1/5 25% 3 yes
28 8 2 25% 3 yes
29 2 100% 4 1 14 yes
30 2 100% 4 1 14 yes
31 30 10% 7 1 30 90%
32 17 1 yes

Dermatol Res, 2022 Volume 4 | Issue 1 | 6 of 13

 Figure 1 PRISMA flow diagram of study selection

Records identified through database

Identification searching (n=3148)
PubMed (n = 305), Embase (n = 881),
Cochrane (n = 402), Scopus: (n= 1560)

Records after duplicates removed

(n =2279) Records excluded
Screening

(n=1921)

Case reported (n=10), Review

(n=25), Sunscreen usage
(n=207), Sunscreen advantage
Records screened (n= 302), Situation description
(n = 2279) (n=60), Other (n=1317)

Full-text articles excluded

Eligibility

Full-text articles assessed (n =337)

for eligibility No plasma concentration or
(n = 358) concentration of urine or
complication with sunscreen
recorded

Studies included in
Included

qualitative synthesis
(n = 21)

Figure 1: PRISMA flow diagram of study selection

human plasma and urine within one day to several years in the ng/mL for females and 300, 20, 20 ng/mL for males, respectively
partial or whole body. [7]. Benzophenone-3 provided higher plasma concentrations
than others. According to Matta et al., using 2 mg/cm2 of several
Result sunscreen preparations (lotions and sprays) in 75% of the body
The study screening process is summarized in the flow diagram (containing oxybenzone, avobenzone, octocrylene, homosalate,
(tableure 1). Among 21 articles for data extraction, 4 reported octisalate, octinoxate, ecamusla) showed plasma concentrations of
maximum plasma concentrations of sunscreen ingredients oxybenzone 169 to 209 ng/ml, avobenzone 1.8 ng/ml, octocrylene
(Tables 1 and 2), 4 articles reported ingredients concentration in 5.7 ng/ml, homosalate 23 ng / ml, octisalate 5.8 ng/ml octinoxate
urine (Tables 3 and 4), and 18 articles reported sunscreen usages 7.9 ng/ml, and ecamusla 1.5 ng/ml [31]. In a comparison between
complications (Tables 5 and 6). lotion and spray formulations used in this study, the lotions
yielded higher active ingredients’ concentrations in plasma.
Sunscreens Plasma concentrations Systemic exposures of all ingredients remained above 0.5 ng/mL
Sunscreen active ingredients - avobenzone, oxybenzone, for more than 50% of participants up to 7 days for avobenzone,
octoclylene, ecamsule, homosalate, octisalate, enzacamene, and octisalate, and octinoxate; 10 days for octocrylene; and 21 days for
octinoxate - are systematically absorbed when applied to human homosalate and oxybenzone [31].
skin. In 2008, Janjua et al. showed that sunscreens with 10% of
each benzophenone-3, octinoxate and enzacamene were absorbed Matta et al. then studied with 48 participants to provide additional
into the blood at maximum plasma concentrations of 187, 7, 16 data on the systemic exposure of the active sunscreens ingredients

Dermatol Res, 2022 Volume 4 | Issue 1 | 7 of 13

following a single application; residual skin amounts during the (benzophenone-4) and para-aminobenzoic acid (PABA) on
wash-out phase; plasma concentrations up to 17 days after the last the face for 2 days, 18% irritation was observed [37]. Hayag
application; and the systemic exposure to additional commonly applied a sunscreen including 10% octocrylene (OCT), 7.5%
used sunscreen ingredients, including octisalate, homosalate, and octyl methoxycinnamate (OMC), and 5% meradimate with SPF
octinoxate. Systemic exposure of all the sunscreens in all products of 30 in 10% of the body area for 7 days and 30 days of follow-
exceeded 0.5 ng/mL on a single application and remained above up caused 90% irritation [38]. Kerr et al., found sulisobenzone
the threshold until 23 hours after application. Systemic exposures (benzophenone-4) and bisoctrizole caused 5% irritation [39].
of all tested actives remained above 0.5 ng/mL in more than Sunscreen lotion containing octyl methoxycinnamate (OMC),
50% of participants up to 7 days for avobenzone, octisalate, and three times a day, caused irritation, immune system disorder,
octinoxate; 10 days for ocotocrylene; and 21 days for homosalate hormonal disruption, and significant stratum corneum DNA
and oxybenzone [32]. Hiller et al. collected plasma and urine damage [40]. Sunscreens as a spray, lotion, and cream including
samples from 20 healthy volunteers before, during, and after a avobenzone, oxybenzone, octocrylene, and ecamsule ingredients
real-life exposure scenario (1st application: 2 mg/cm2; 2nd and 3rd with different combinations applied on 75% of the body caused
(after 2 and 4 h): 1 mg/cm2 each) using a commercial sunscreen 17% rash [31]. In addition, 30% of participants using sunscreen
formulation for one day. They reported avobenzone concentrations containing polyethylene glycols, octyl salicylate, bemotrizinol,
as 11.7 ng / mL and octocrylene as 25.0 ng /mL in human plasma ensulizole, methyl methacrylate (MMA), homosalate, titanium
[33]. dioxide, and avobenzone reported rash in a 90-day follow-up
study in Thailand [41]. In the conducted studies by English
Urine Concentration et al., a patch test containing 2% chemical UV filters was
Kunisue et al. reported the highest concentration of hydroxylated used for 2 days on 280 participants, Choi et al. used to patch
benzophenone metabolite (2, 4 dihydroxybenzophenone) in urine and photopatch containing 25% octylmethoxycinnamate,
(23 ng/ml) [34]. The average excreted benzophenone-3 in urine was butylmethoxydibenzoylmethane, and octyltriazone for 2 weeks,
11 mg/ml, upon sunscreen application containing 4% BP-3 after on 200 participants, 5 and 4 % of the participants showed rash
48 h which showed high skin permeability [35]. The lipophilic UV respectively [42,43]. Also, using 2 mg/cm2 of sunscreen cream
filter octocrylene and its metabolite 2-cyano-3, 3-diphenylacrylic in the full-body for 4 days induced hormonal disturbance [7].
acid showed much slower elimination than other hydrophilic UV Daily sunscreen use with SPF 8 and 15, 17 caused a reduction in
filters, avobenzone, and octocrylene were detected in more than 25-hydroxyvitamin D levels [44-46].
20% of urine samples [33].
Discussion
Accumulation of sunscreens and their metabolites in the human Plasma concentration
body occurs when exposures were repeated for several consecutive Sunscreen preparations are considered cosmetics in some countries,
days. Application of sunscreen preparations containing 10% of each and there appears minimal in-depth toxicity evaluations to support
BP-3, octinoxate, and enzacamene (2 mg/cm2) in the total body per their life long use safety. FDA recognizes certain requirements to
day for a week resulted in mean urine concentrations of 60, 5, 5 support sunscreen safety and effectiveness [47]. Most sunscreens
ng/ml for females and 140, 7, 8 ng/ml for males, respectively [7]. contain organic chemicals [6-8] with various amounts in sunscreen
Repeated whole-body benzophenone-3 application increased BP3 products, but acceptable levels are as high as 15% [23]. FDA
excretion after 2 days, which reached steady-state after 3 to 5 days, issued a proposed regulation that considers most sunscreen
and then decreased [7]. Average urinary levels of octocrylene and active ingredients which are currently used are not classified as
avobenzone were 7.9 and 1.7 ng / ml, respectively, after 6 days of generally recognized as safe and effective (GRASE) due to a
application, 4 times daily [33]. lack of adequate safety information in the US [48]. The rule also
discussed the safety evidence recommended to support a decision
Adverse Effect on whether certain active ingredients are GRASE, including the
The adverse effect reported with sunscreens applications were need for information on human absorption. The key objective of
rash, irritation, immune system dysfunction, significant stratum the maximum usage trial is to help the FDA assess the expected
corneum DNA damage, hormonal disruption, decreased levels level of human risk [48]. As mentioned, FDA sunscreen guidance
of 25-hydroxy vitamin D, and hindered effective sweating. In a on safety and efficacy accepted 0.5 ng/ml in the bloodstream as
randomized controlled trial conducted by Lindstrom, long-term the regulatory threshold of sunscreen active ingredients [47].
sunscreen use was assessed on mortality of 1,621 Australian Nonetheless, the public Access for Sunscreens Coalition proposed
adults over 21 years old [36]. Results showed a higher mortality a higher concentration of sunscreen active ingredients in the
rate in the discretionary sunscreen group, but cancer death bloodstream as a safety threshold of 20–200 folds (10–100 ng/
was higher in the daily sunscreen group [36]. Four studies ml). Ingredients absorption in the bloodstream can vary depending
reported skin rash, six irritation, three vitamin D decrease, on factors including physicochemical characteristics of the active
and three hormonal disruption as an adverse effect following ingredient, formulation properties, and stratum corneum thickness,
sunscreen use. In a study performed on 23 women by Beleznay and structure [49-52].
K et al., after application of sunscreen including sulisobenzone

Dermatol Res, 2022 Volume 4 | Issue 1 | 8 of 13

Eight active ingredients - avobenzone, octoclylene, ecamsule, Weaknesses and Strengths
homosalate, octisalate, enzacamene, octinoxate, and oxybenzone The trials presented in this review have various weaknesses
- were found in the blood more than 0.5 ng/mL after 1-4 and strengths [7,31-46,56,61]. In most studies presented, the
daily application on 75% of the body's surface. Oxybenzone number of participants was small and the results are likely to be
(benzophenone-3) was detected at a higher level than other UV incomplete. In most studies, the research environment was the
filters in plasma. Relatively, low human skin penetration was external environment to make the effect of sunlight on the cases
observed for octyl salicylate [53]. Oxybenzone, one of the most more realistic, but in these studies, influential factors such as heat,
lipophilic UV filters highly penetrates into the skin. Data on humidity, wind, and cloud cover are not controlled. The type of
safety assessment, internal organ carcinogenicity potential and formulation and the type of Fitzpatrick skin may affect sunscreen
reproductive effects, and clinical studies are essential. absorption. However, in some studies, Fitzpatrick skin types were
not considered. Utilizing strengths and weaknesses of previous
Skin penetration studies on titanium dioxide (TiO2) nanoparticles studies will aid planning the next generation of research.
showed that they cannot infuse unbroken skin and can only be found
in the stratum corneum and epidermis and do not reach the blood Conclusion
or peripheral organs [54,55]. Consequently, mineral sunscreens Sunscreens reduce the harmful sunlight risks on skin. Adverse
such as zinc oxide and TiO2 do not significantly penetrate the skin effects of sunscreen have not been conclusively documented in
and bloodstream and are usually considered safe [51]. long term. To reduce the potential adverse effects, high systemic
absorption ingredients might be substituted with less penetrating
According to this review, most organic sunscreen ingredients substances and those that can fully excreted.
are absorbed to a greater extent than FDA anticipated and may
accumulate in internal tissues. Consumers should use these substances just in sun-exposed body
areas to minimize their potential accumulation.
Urine concentration
After sunscreen application on skin, organic sunscreens such as Sunscreen prescribers should pay close attention to sunscreen
avobenzone, benzophenone-3, octocrylene, enzacamene, and ingredients, particularly in children, pregnant women, and people
octinoxate were found in urine [7,26,33,34]. Benzophenone-3 with a history of skin diseases, hormonal disorders and vitamin
indicated the highest urine concentration among the UV filters D deficiency. Also, consider combining these substances with
[34]. nanotechnology that remain only in the epidermis and may not enter
the blood and circulation system, and prevent their accumulation
Adverse Effect
in the body tissues and potential side effects. Together, life long
Irritation and rash are common sunscreen complications
use of sunscreens and high organic compounds percutaneous
widely reported [26,31,32,37-39,42,43). Sunscreens containing
penetration suggest a wisdom need of additional acute and long
avobenzone, oxybenzone, ecamsule, para-aminobenzoic acid
term toxicologic evaluations.
(PABA), and octocrylene cause rash and irritation [31,38,42,43].
A sunscreen lotion containing octyl methoxycinnamate (OMC)
caused immune system dysfunction, stratum corneum DNA References
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 human plasma and urine after repeated whole‐body topical 23. Wang J, Ganley CJ. Safety threshold considerations for
application. Journal of the European Academy of Dermatology sunscreen systemic exposure: a simulation study. Clinical
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12. Berton TR, Pavone A, Fischer SM. Ultraviolet-B irradiation benzophenone-3 and reproductive toxicity: A systematic
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application under maximal use conditions on plasma
group. British Journal of Dermatology. 2006; 155: 737-747.
concentration of sunscreen active ingredients: a randomized
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-cosmetics--mechanisms--methodology: drugs--cosmetics--
32. Matta MK, Florian J, Zusterzeel R, et al. Effect of Sunscreen
mechanisms--methodology: CRC Press. 1999.
Application on Plasma Concentration of Sunscreen Active
18. Driver J, Tardiff RG, Sedik L, et al. In vitro percutaneous Ingredients: A Randomized Clinical Trial. Jama. 2020; 323:
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Epidemiol. 1993; 3: 277-284.
33. Hiller J, Klotz K, Meyer S, et al. Systemic availability of
19. Feldmann RJ, Maibach HI. Absorption of some organic lipophilic organic UV filters through dermal sunscreen
compounds through the skin in man. Journal of investigative exposure. Environment international. 2019; 132: 105068.
dermatology. 1970; 54: 399-404. 34. Kunisue T, Chen Z, Buck Louis GM, et al. Urinary
20. Maibach HI, Feldman RJ, Milby TH, et al. Regional variation concentrations of benzophenone-type UV filters in US women
in percutaneous penetration in man. Pesticides. Arch Environ and their association with endometriosis. Environmental
Health. 1971; 23: 208-211. science & technology. 2012; 46: 4624-4632.
21. Wester RC, Maibach HI. Cutaneous pharmacokinetics: 10 35. Gustavsson Gonzalez H, Farbrot A, Larkö O. Percutaneous
steps to percutaneous absorption. Drug Metabolism Reviews. absorption of benzophenone‐3, a common component of
1983; 14: 169-205. topical sunscreens. Clinical and experimental dermatology.
22. Wester RC, Melendres J, Sedik L, et al. Percutaneous 2002; 27: 691-694.
absorption of salicylic acid, theophylline, 2, 4-dimethylamine, 36. Lindstrom AR, von Schuckmann LA, Hughes MCB, et al.
diethyl hexyl phthalic acid, and p-aminobenzoic acid in the Regular Sunscreen Use and Risk of Mortality: Long-Term
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Toxicol Appl Pharmacol. 1998; 151: 159-165. 2019; 56: 742-746.

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37. Beleznay K, de Gannes G, Kalia S. Analysis of the prevalence 49. Ates G, Steinmetz FP, Doktorova TY, et al. Linking existing
of allergic contact dermatitis to sunscreen: A cohort study. in vitro dermal absorption data to physicochemical properties:
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38. Hayag MV, Chartier T, DeVoursney J, et al. A high SPF the safety evaluation of cosmetic ingredients with low dermal
sunscreen's effects on UVB-induced immunosuppression of bioavailability. Regulatory Toxicology and Pharmacology.
DNCB contact hypersensitivity. Journal of dermatological 2016; 76: 74-78.
science. 1997; 16: 31-37. 50. Bernauer U, Bodin L, Chaudry Q, et al. The SCCS notes of
39. Kerr AC, Niklasson B, Dawe RS, et al. A double‐blind, guidance for the testing of cosmetic ingredients and their
randomized assessment of the irritant potential of sunscreen safety evaluation-10th revision SCCS/1602/18–Final version.
chemical dilutions used in photopatch testing. Contact 2019.
dermatitis. 2009; 60: 203-209. 51. Burli A, Law RM, Rodriguez J, et al. Organic compounds
40. Sharma A, Bányiová K, Vrana B, et al. Investigation of cis- percutaneous penetration in vivo in man: Relationship to
trans isomer dependent dermatotoxicokinetics of UV filter mathematical predictive model. Regul Toxicol Pharmacol.
ethylhexyl methoxycinnamate through stratum corneum in 2020; 112: 104614.
vivo. Environmental Science and Pollution Research. 2017; 52. Touitou E, Godin B. Skin nonpenetrating sunscreens for
24: 25061-25070. cosmetic and pharmaceutical formulations. Clinics in
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sensitization potential of sunscreen after ablative fractional 53. Walters K, Brain K, Dressler W, et al. Percutaneous penetration
skin resurfacing using modified human repeated insult patch of N-nitroso-N-methyldodecylamine through human skin in
test. Journal of Dermatological Treatment. 2015; 26: 485-488. vitro: application from cosmetic vehicles. Food and chemical
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Octylmethoxycinnamate, Butylmethoxydibenzoylmethane, 54. Crosera M, Prodi A, Mauro M, et al. Titanium dioxide
and Octyltriazone Sunscreens by Human Repeated Insult nanoparticle penetration into the skin and effects on HaCaT
Patch Tests to Compare the Shelanski and Maximization cells. International journal of environmental research and
Tests. Korean J Dermatol. 2003; 41: 1592. public health. 2015; 12: 9282-9297.
43. English J, White I, Cronin K. Sensitivity to sunscreens. 55. Senzui M, Tamura T, Miura K, et al. Study on penetration of
Contact dermatitis. 1987; 17: 159-162. titanium dioxide (TiO2) nanoparticles into intact and damaged
44. Farrerons J, Barnadas M, Rodriguez J, et al. Clinically skin in vitro. The Journal of toxicological sciences. 2010; 35:
prescribed sunscreen (sun protection factor 15) does not 107-113.
decrease serum vitamin D concentration sufficiently either 56. Aburto-Corona J, Aragón-Vargas L. Sunscreen use and sweat
to induce changes in parathyroid function or in metabolic production in men and women. Journal of athletic training.
markers. The British journal of dermatology. 1998; 139: 422- 2016; 51: 696-700.
427. 57. Broekmans WM, Vink AA, Boelsma E, et al. Determinants of
45. Faurschou A, Beyer D, Schmedes A, et al. The relation skin sensitivity to solar irradiation. Eur J Clin Nutr. 2003; 57:
between sunscreen layer thickness and vitamin D production 1222-1229.
after ultraviolet B exposure: a randomized clinical trial. British 58. Dornelles S, Goldim J, Cestari T. Determination of the
Journal of Dermatology. 2012; 167: 391-395. minimal erythema dose and colorimetric measurements as
46. Marks R, Foley PA, Jolley D, et al. The effect of regular indicators of skin sensitivity to UV-B radiation. Photochem
sunscreen use on vitamin D levels in an Australian population: Photobiol. 2004; 79: 540-544.
results of a randomized controlled trial. Archives of 59. Heckman CJ, Chandler R, Kloss JD, et al. Minimal Erythema
dermatology. 1995; 131: 415-421. Dose (MED) testing. J Vis Exp. 2013; 75: e50175.
47. Food U & Administration D. Guidance for industry: 60. Yuan C, Wang XM, Tan YM, et al. Effects of sunscreen
nonprescription sunscreen drug products–safety and on human skin's ultraviolet radiation tolerance. J Cosmet
effectiveness data November. 2016. Dermatol. 2010; 9: 297-301.
48. Food U & Administration D. Sunscreen drug products for 61. Berne B, Ros AM. 7 years experience of photopatch testing
over-the-counter human use: proposed rule. Fed Regist. 2019; with sunscreen allergens in Sweden. Contact dermatitis. 1998;
84: 6204-6275. 38: 61-64.

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Graphic Abstract

Supplement Table 1: Active sunscreen ingredients are approved by the FDA (Preclinical PK/PD and Toxicology Services for Sunscreen). All are
chemical except Titanium dioxide and Zinc Oxide.
Mechanism of sun prevention
FDA Monograph Sunscreen Ingredients
UVA UVB
Aminobenzoic acid (PABA) 
Avobenzone  
Cinoxate  
Dioxybenzone  
Ecamsule  
Homosalate 
Menthylanthranilate  
Octocrylene  
Octyl methoxycinnamate  
Octyl salicylate 
Oxybenzone  
Padimate O 
Phenylbenzimidazole 
Sulisobenzone  
Titanium dioxide  
Trolamine salicylate 
Zinc Oxide  

Dermatol Res, 2022 Volume 4 | Issue 1 | 12 of 13

Supplement Table 2: Search Strategies.
Database Search strategy
((("sunscreen" OR "sun-screen" OR "sunscreen application" OR "Sunscreening Agents" [Pharmacological Action] OR "Sun Protection Factor"[Mesh])
AND ("adverse effects" OR "Sunscreening Agents/adverse effects"[Mesh] OR "adverse drug reaction" OR "poisoning" OR "Sunscreening Agents/
poisoning"[Mesh] OR "intoxication" OR "Toxi*" OR "Sunscreening Agents/toxicity"[Mesh] OR "Permeability" OR "skin permeability" OR "hazard"
PubMed OR "health hazard" OR "Safety"[Mesh] OR "risk assessment" OR "drug concentration" OR "Blood Circulation"[Mesh] OR "circulation")) AND
("Pragmatic Clinical Trial" [Publication Type] OR "Controlled Clinical Trial" [Publication Type] OR "Clinical Trial, Phase IV" [Publication Type]
OR "Clinical Trial, Phase III" [Publication Type] OR "Clinical Trial, Phase II" [Publication Type] OR "Clinical Trial, Phase I" [Publication Type] OR
"Randomized Controlled Trial" [Publication Type] OR "Clinical Trial" [Publication Type] OR "Clinical Trial Protocol" [Publication Type]))
TITLE-ABS-KEY ( ( {sunscreen} OR {sun-screen} OR {sunscreening agents} OR {sun protection factor} ) AND ( {adverse effects} OR
{adverse drug reaction} OR {poisoning} OR {intoxication} OR {toxicity} OR {permeability} OR {skin permeability} OR {hazard} OR
Scopus
{health hazard} OR {safety} OR {risk assessment} OR {drug concentration} OR {blood circulation} OR {circulation} ) AND ( {human} OR
{man} OR {men} OR {woman} OR {women} ) ) AND ( LIMIT-TO ( DOCTYPE , "ar" ) )
('human'/exp OR 'homo sapiens' OR 'human' OR 'human being' OR 'human body' OR 'human race' OR 'human subject' OR 'humans' OR 'man
(homo sapiens)') AND ('sunscreen'/exp OR 'anti sunburn preparation' OR 'antisunburn agent' OR 'sun burn protective agent' OR 'sun
cream' OR 'sun protection factor' OR 'sun protective agent' OR 'sun protective factor' OR 'sun screen' OR 'sunburn oil' OR 'sunburn protecting
agent' OR 'suncream' OR 'sunscreen' OR 'sunscreen agent' OR 'sunscreen product' OR 'sunscreen products' OR 'sunscreening agents') AND
('adverse event'/exp OR 'adverse effect' OR 'adverse effects' OR 'adverse event' OR 'adverse events' OR 'adverse reaction' OR 'intoxication'/
exp OR 'mptp poisoning' OR 'acute intoxication' OR 'carbon tetrachloride poisoning' OR 'chronic intoxication' OR 'endogenous
intoxication' OR 'intoxication' OR 'intoxification' OR 'overdose' OR 'poisoning' OR 'poisoning, mptp' OR 'toxic injury' OR 'toxicosis' OR 'toxicity'/
exp OR 'hypertoxicity' OR 'subacute toxicity' OR 'tissue toxicity' OR 'toxic actions' OR 'toxic effect' OR 'toxicity' OR 'toxigenicity' OR 'permeability'/
Embase exp OR 'permeability' OR 'permeability constant' OR 'tissue permeability' OR 'skin permeability'/exp OR 'cutaneous permeability' OR 'permeability,
skin' OR 'skin permeability' OR 'skin water permeability' OR 'hazard'/exp OR 'danger' OR 'dangerousness' OR 'hazard' OR 'health hazard'/exp
OR 'hazard, health' OR 'health hazard' OR 'health risk' OR 'safety'/exp OR 'safety' OR 'safety management' OR 'safety precaution' OR 'safety
protection' OR 'safety regulation' OR 'risk assessment'/exp OR 'assessment, safety' OR 'risk adjustment' OR 'risk analysis' OR 'risk assessment' OR 'risk
evaluation' OR 'safety assessment' OR 'circulation'/exp OR 'blood circulation' OR 'circulation' OR 'circulatory tract' OR 'blood level'/exp OR 'blood
concentration' OR 'blood level' OR 'plasma concentration' OR 'plasma level' OR 'serum concentration' OR 'serum level' OR 'urine level'/exp OR 'urinary
level' OR 'urine level') AND ('clinical trial'/exp OR 'clinical drug trial' OR 'clinical trial' OR 'major clinical trial' OR 'trial, clinical' OR 'randomized
controlled trial'/exp OR 'controlled trial, randomized' OR 'randomised controlled study' OR 'randomised controlled trial' OR 'randomized controlled
study' OR 'randomized controlled trial' OR 'trial, randomized controlled')
('sunscreen' OR 'sun-screen' OR 'sunscreen application' OR 'sunscreening agents' OR 'sun protection factor') AND ('adverse effects' OR 'adverse drug
Cochrane reaction' OR 'poisoning' OR 'intoxication' OR 'toxi*' OR 'permeability' OR 'skin permeability' OR 'hazard' OR 'health hazard' OR 'safety' OR 'risk
assessment' OR 'drug concentration' OR 'blood circulation' OR 'circulation') AND ('humans' OR 'human')

© 2022 Putri MK. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License

Dermatol Res, 2022 Volume 4 | Issue 1 | 13 of 13

856611
research-article2019
CMSXXX10.1177/1203475419856611Journal of Cutaneous Medicine and SurgeryLi et al

Feature Article

Journal of Cutaneous Medicine and Surgery

Sunscreen Application, Safety, 1­–13

© The Author(s) 2019
Article reuse guidelines:
and Sun Protection: The Evidence [Link]/journals-permissions
DOI: 10.1177/1203475419856611
[Link]
[Link]

Heidi Li1 , Sophia Colantonio1,2, Andrea Dawson1,2,

Xing Lin1,2, and Jennifer Beecker1,2

Abstract
Recently in Canada, there has been an effort to create consistent messaging about sun safety as there is a lack of up-to-
date evidence-based guidelines regarding sun-protection measures. This review aimed to provide updated, evidence-based
recommendations on sunscreen application, safety, and sun protection regarding the following topics for which there is
clinical uncertainty: physical barriers, sunscreen properties, sunscreen application, and risk-benefit analysis.

Keywords
application, guidelines, photodamage, photoprotection, review, skin cancer, SPF, sun protection, sun protection factor,
sunscreen

Introduction Methods
Skin cancer is the most common form of cancer in Canada, Literature Search
with non–melanoma skin cancer (NMSC) alone accounting
for at least 40% of new cancer cases.1 In 2014, an estimated A list of broad topics on sunscreen use and sun-protection
6500 new cases of melanoma and 76 100 cases of NMSC methods was formulated after a preliminary survey between
occurred in Canada. The incidence of skin cancer is pro- the authors and members of the Dermatology Division at The
jected to rise in the coming decades because of the aging Ottawa Hospital, a Canadian tertiary care hospital. The pro-
population.2 Since most skin cancers are preventable by posed topics included “sunscreen application amount,”
reducing natural and artificial ultraviolet (UV) radiation “application frequency,” “application timing,” “SPF recom-
exposure,3 public education on and advocacy for sun pro- mendation,” “formulation of sunscreens,” “organic vs inor-
tection are essential. Two key messages regarding sun- ganic sunscreens,” “water-resistance of sunscreens,” “lip
safety education are the regular use of sunscreen and protection,” “physical barriers,” “population factors for sun-
physical protective agents, such as clothing, hats, sun- screen use,” and “harms and benefits of sunscreens.”
glasses, and shade.4 A search for relevant studies in MEDLINE (1946 to
Sunscreens have gained tremendous commercial success December 2018) was performed. Our search strategy used all
since their introduction in the United States in 1928 and have combinations of the following key terms: “sunscreening
been incorporated into various moisturizers, makeup, and lip agents,” “application,” “skin pigmentation,” “administra-
products. Worldwide, sun-care product sales have increased tion,” “protective clothing,” “sunburn,” “water resist,” “sun-
7% on average per year over the last 5 years.4 burn,” “sun protection factor,” “skin neoplasms,” “skin
The efficacy of protection by sunscreens has been widely aging,” “photoaging,” and “lip.” Publications were limited to
accepted as indicated by the sun protection factor (SPF), first meta-analyses, systematic reviews, randomized controlled
adopted in 1978 by the US FDA. In Canada, sunscreens are trials, guidelines, comparative studies, evaluation studies, or
approved and regulated by Health Canada. To promote uni-
formity of public health messages in Canada, a National 1
University of Ottawa, ON, Canada
Consensus on Sun Safety Messages was developed in 2016.5 2
Division of Dermatology, The Ottawa Hospital, ON, Canada
In addition, the FDA and Health Canada alike have modified
Corresponding Author:
their sunscreen monographs in the past 5 years.
Jennifer Beecker, The Ottawa Hospital, The Division of Dermatology,
The purpose of this study was to assess the current litera- 737 Parkdale Ave, 4th Floor, Parkdale Clinic, Ottawa, ON K1Y 4E9,
ture on sun-protection measures and methods to derive a set Canada.
of best-practice recommendations. Email: jbeecker@[Link]
2 Journal of Cutaneous Medicine and Surgery 00(0)

multicentre studies in the English language after 1946. A Results

manual search was also conducted based on references cited
in selected articles generated by the literature search. The initial search yielded 424 studies. After screening the
titles and abstracts for relevance, 84 articles were selected for
full-text review, as summarized in Supplementary Table 4.
Research Questions Here, we review the evidence for each research question to
support the recommendations summarized in Table 1.
The abstracts and titles of articles yielded from the search
were screened to select relevant articles that addressed the
following research questions for subsequent full-text review: Physical Barriers
Is Ultraviolet Protective Clothing Superior to Regular Clothing?
1. Physical barriers Protective clothing is a simple method of photoprotection.7
a. Is UV protective clothing superior to regular Canadian consumer guidelines for UV protection clothing
clothing? refer to the ultraviolet protection factor (UPF), a standardized
b. What minimum level of UV protection is needed in vitro measurement of the ultraviolet A (UVA) and ultravio-
in sunglasses? let B (UVB) protection of clothing.8 Currently, UPFs 15 and
2. Sunscreen properties 20 are rated as good photoprotection; UPF 25, 30, and 35 as
a. What is the recommended SPF of sunscreens? very good; and UPF 40, 45, 50, and 50+ as excellent. There
b. What is the preferred vehicle of sunscreens? are no Canadian guidelines as to the ideal minimum UPF fac-
c. Should inorganic or organic sunscreens be used? tor, whereas European standards recommend UPF 40+.
d. When should water-resistant sunscreens be UPF ratings are affected by multiple heterogeneous
used? ­factors, including weave density, composition, colour, fabric
e. Lip protection thickness, stretch, moisture, and fabric condition.9 Two
f. Expiry date ­studies10,11 have demonstrated that thicker and heavier-
3. Sunscreen application weight clothing with dark colourants provided more protec-
a. What amount of sunscreen is appropriate to tion. Similarly, an in vitro study12 found that UPF of a replica
apply? England football shirt with white vertical bands of varying
b. How frequently should sunscreen be reapplied? thickness had a UPF of 5 for the thinner bands and 11 for the
Does physical activity affect the frequency of thicker bands, highlighting the importance of clothing thick-
application? ness. For fabric composition, numerous studies demon-
c. How long before sun exposure should sunscreen strated that Lycra/elastane fabrics were the most likely to
be applied? have UPFs of 50 or higher, followed by plastic, nylon, and
d. Does application of sunscreen vary for different polyester.9 Thus, it is important for consumers to check the
skin types? UPF tag when selecting garments for UV-protection pur-
4. Risk-benefit analysis poses. If UPF tags are not available, generally consumers
a. Is sunscreen harmful (ie, risks of compounds/ should choose garments with greater fabric weight, thick-
ingredients)? ness, tighter weave, darker colours, and those of made of
b. Are sunscreens safe for infants? Lycra/polyester, as these characteristics typically result in
c. Does sunscreen prevent skin damage/aging/ greater photoprotection.7 Additionally, consumers should be
wrinkles? aware that garments that are worn thin, wet, or stretched may
d. Does sunscreen prevent skin cancer? offer reduced UV protection as UPF values decreases with
stretch, wetness, and numerous washes.7
Although all types of clothing provide some degree of
Critical Appraisal and Recommendation
UV-light protection, recent studies have demonstrated that
The research design and quality of all relevant publications some regular clothing garments do not provide sufficient UV
were assessed using the Canadian Task Force on Preventive protection.13 UV-protective clothing is specifically designed
Health Care (CTFPHC) grading of recommendations, assess- to block out UV light and may provide more effective broad-
ment, development, and evaluation (GRADE) definitions spectrum photoprotection. Numerous studies, including two
(see Supplementary Tables 1 and 2).6 The levels of evidence in vitro studies14,15 found that athletic clothing (yellow soc-
for all articles included in the systemic review are presented cer jersey, blue shorts, sweatshirt, baseball cap, cycling jer-
in Supplementary Table 3. Studies relevant to the same topic seys) all offered excellent protection. There are only a few
were evaluated together to derive an overall recommenda- studies comparing the photoprotection of regular clothing
tion. The level of evidence for each recommendation was with that of photoprotective clothing. A small study16 dem-
ranked based on the CTFPHC GRADES of Recommendation onstrated that regular clothing provided similar UVA/UVB
as “strong” or “weak” (see Table 1).6 protection as photoprotective clothing, although their study
Li et al 3

Table 1. Summary of Recommendations for Each Research Question and Strength of Recommendations as Evaluated Using the
CTFPHC GRADE System.

Research Question Recommendation Strength

Physical Barriers UV protective clothing is superior to regular clothing as it provides excellent consistent Weak
light-weight photoprotection with clear UPF ratings.
When choosing regular clothing items with no UPF tags, choose garments with tighter Strong
weaves, increased fabric weight, thickness, darker colours, and Lycra/polyester
composition and that cover more skin. Moisture, fabric stretching, and fabric degradation
could also decrease the UPF factor.
Sunglasses that provides UV absorption up to 400 nm should be worn during daily activities Weak
(eg, driving) in conjunction with hats. In particular, this message should be reinforced with
men and minorities, the most at-risk groups.
SPF A broad-spectrum sunscreen with UVA and UVB filters and SPF of at least 30 should Strong
be applied, and even higher SPF sunscreens may be used to compensate for common
underapplication of sunscreen.
Patient education is needed on the meaning of SPF and other factors affecting effectiveness Strong
of sunscreen apart from the SPF value alone.
Vehicle of Sunscreen Water-in-oil emulsion is the recommended formulation of sunscreens to achieve highest Weak
SPF and water resistance.
Organic vs Inorganic A broad-spectrum sunscreen containing a balance of UVA and UVB filters is recommended, Strong
Sunscreens regardless of whether the components are organic or inorganic.
When using sunscreens with primarily nonmicronized inorganic filters, education to avoid Strong
underapplication is especially important.
Water Resistance Water-resistant sunscreen (for 40 or 80 minutes) should be worn in conditions in which Strong
there is significant sweating, water immersion, increased skin friction via physical contact,
or contact with sand.
Lip Protection Lip sunscreen should be applied generously to cover the whole lip. Strong
High-SPF products (≥ 30) and reapplication should be used to compensate for Strong
underapplication.
Expiry Date Do not use sunscreens that are past the manufacturer-specified expiry date or Weak
recommended period after opening. Sunscreens should be stored at room temperature
to ensure stability.
Sunscreen Apply liberally (approximately 45 ml) to all exposure areas. Strong
Application Reapplication within an 8-hour period is necessary only after activities that may remove the Strong
sunscreen layer (swimming, sweating, friction).
Apply prior to sun exposure and at least 20 minutes prior to water activities. Weak
Individuals of colour should use photoprotection, including sunscreen. Weak
Sunscreen Safety Safe overall with a favourable risk-benefit profile. Strong
Stratum corneum is an effective barrier, thus systemic absorption should not be a concern. Strong
Risks: photoallergy (most common, but rare), reproductive toxicity, decreased fertility Strong
(lack of evidence), hazardous to coral (more research needed; direct association with
sunscreen not established).
Limit the use of sunscreen in children younger than age 6 months. Weak
Benefits Sunscreen prevents photoaging. Strong
Sunscreen prevents melanoma and non–melanoma skin cancer. Strong

Abbreviations: CTFPHC, Canadian Task Force on Preventive Health Care; GRADE, grading of recommendations, assessment, development, and
evaluation; SPF, sun protection factor; UPF, ultraviolet protection factor; UV, ultraviolet; UVA, ultraviolet A; UVB, ultraviolet B

was very limited in terms of the number and type of garments cost, whereas typical normal clothing may provide inade-
tested. Furthermore, UV-protective clothing is also designed quate to excellent protection.
to be more lightweight and breathable compared with normal Recommendation: There is fair evidence to support the
clothing, making it the ideal consumer choice for hot sum- use of photoprotective clothing as it provides excellent con-
mer weather and outdoor physical activities. Although cer- sistent photoprotection with clear UPF ratings, allowing the
tain items of normal clothing such as denim jeans provide a consumer to know the exact amount of photoprotection
high UPF (1700), they are not practical for athletic activities.9 offered. Although certain regular clothing items may pro-
Although the evidence is limited, UPF clothing provides vide comparable photoprotection, regular clothing is more
excellent photoprotection with few disadvantages other than variable with a broader spectrum of photoprotection
4 Journal of Cutaneous Medicine and Surgery 00(0)

ranging from inadequate to excellent, making it potentially visible minorities and men were significantly less likely to
difficult for the consumer to definitively evaluate the pho- wear sunglasses than Caucasians and women, respec-
toprotection offered. In addition, as it may be difficult to tively. 63% of Caucasians vs 44% of visible minorities
make regular clothing lightweight, photoprotective cloth- reported always wearing sunglasses, and women were
ing is an ideal choice for consumers in hot summer weather, 78% more likely to wear sunglasses than men.21 A system-
if affordable. When choosing regular clothing items with atic review22 found that sunglasses were the most com-
no UPF tags, consumers should choose garments with monly reported sun-protective behaviour of outdoor
tighter weaves, increased fabric weight, thickness, darker workers; however, this varied widely between groups of
colours, and of Lycra/polyester composition and that cover workers as 80% of lifeguards wore sunglasses compared
more skin. A practical tip to assess regular clothing is to with British or Japanese construction workers, who rarely
hold the garment up to a light source to see whether the wore sunglasses.
light shines through. Consumers should also be aware that Recommendation: For daily activities, patients should
moisture, fabric stretching, and fabric degradation decrease wear general-purpose sunglasses in conjunction with a
the UPF factor. Further studies that compare a variety of broad-brimmed hat to reduce the amount of UVR reaching
UPF clothing and normal clothing under different condi- the eyes. Better-quality studies are needed to further quan-
tions are needed. tify the absolute risk reduction of wearing sunglasses and
Grade of Recommendation: STRONG in combination with broad-brimmed hats. Physicians
should specifically emphasize the importance of sun-
Minimum Protection in Sunglasses. Chronic UV radiation glasses to groups who are most at risk, namely individuals
(UVR) is a known risk factor for cataracts, age-related macu- who experience high-UV occupational exposure as well as
lar degeneration, and pterygium.2 There is also the risk of men and minorities. Greater efforts should be made to
skin cancer involving the delicate skin adjacent to the eye simplify labelling so patients can easily identify the pur-
that is typically not protected by sunscreen. The Canadian pose of sunglasses (cosmetic, general purpose, or special
sunglass industry is self-regulated, and manufacturers com- activity).
ply with voluntary standards when classifying their sun- Grade of Recommendation: STRONG
glasses as cosmetic (block 0%-60% visible light and UVA
and 87.5%-95% of UVB), general purpose for daily activi-
Sunscreen Properties
ties (block 60%-92% visible and UVA and 95%-99% of
UVB), or special purpose, ie, for skiing (block up to 97% of What is the Recommended Sun-Protection Factor of Sunscreens?
visible light, up to 98.5% of UVA, and at least 99% of UVB History of Sun-Protection Factor and Increasing Sun-Protection
rays), as outlined in Health Canada 2010 guidelines. How- Factor. The ideal SPF to recommend to the public has been
ever, Dain et al.17 demonstrated that 17% of the 646 pairs of difficult to define. The Canadian Dermatology Association
sunglasses tested failed to meet voluntary standards, despite (CDA) currently recommends using broad-spectrum sun-
being labelled as such. screens with SPF values of 30 or higher. This message is now
Health Canada 2010 guidelines recommend only general- echoed throughout Canada based on the National Consensus
purpose sunglasses for driving and special-purpose glasses Process on Recommended Core Content for Sun Safety Mes-
for prolonged sun exposure. General-purpose sunglasses are sages in Canada.
often marketed as “UV absorption up to 400 nm,” the equiv- Although there is a common misconception that SPF
alent of 100% UV absorption. values are multiplicative (SPF 30 sunscreen is in fact not
Ophthalmologists and optometrists also recommend the twice as effective compared with SPF 15), there is abun-
combination of a hat with sunglasses to minimize light from dant evidence suggesting that higher SPF is indeed more
entering from the side or top of sunglass frames and then effective at sun protection. A randomized, double-blind,
reflecting off the inner surface of the lens and into the eye.18 split-face, natural sunlight exposure clinical trial23 demon-
A study by Sliney et al19, using simulated ocular geometry, strated that SPF 100+ sunscreen was significantly more
demonstrated that the human eye receives at least 5% of the effective in protecting against sunburn than SPF 50+ sun-
UVR dose when wearing clear lenses opaque to the UVR screen, with 55.3% of their participants more sunburned on
because of the lack of protection above and to the sides of the SPF 50+ protected side compared with 5% on the SPF
sunglasses. This is also why the “wrap-around” style of sun- 100+ protected side. In addition, 40.7% exhibited
glasses is often recommended. increased erythema scores on the SPF 50+ -protected side
Patients should be aware that darker sunglasses do not as compared with 13.6% on the SPF 100+-protected side.
necessarily provide superior ocular UV protection, as darker Similarly, Russak and colleagues demonstrated statisti-
glasses could result in greater pupil dilation and increased cally significantly lower cases of sunburn with application
UV exposure to the lens.2 of SPF 85 sunscreen compared with SPF 5024 and Pissavini
Culture may influence sunglasses usage; this may be a and Diffey showed that SPF 30 application had only 11%
consideration for targeted sun-awareness campaigns. A of skin exhibiting erythema as compared with 46% with
cross-sectional study of US postal workers20 found that SPF 15.25
Li et al 5

Sun-Protection Factor and Application of Sunscreen. Numer- water contact.33 The efficacy of an O/W emulsion is dimin-
ous studies have demonstrated that the typical underap- ished as soon as it comes into contact with water.33 However,
plication of sunscreen ranges from 20% to 50% of the as W/O emulsions generally contain more oils than water,
recommended 2 mg/cm2.26 The exact relationship between they should be avoided on oily skin.34 Of note, certain W/O
SPF and the amount of sunscreen applied, however, is contro- formulations with different concentration of filters may
versial, as some studies of sunscreens with SPF less than 50 absorb oil excess and thus may also have noncomedogenic
have demonstrated an exponential relationship27,28 whereas properties.34
other studies with high-SPF sunscreens (≥ 70) have reported Recommendation: The W/O emulsion is the recom-
a linear relationship.29,30 Regardless, all studies confirmed mended formulation for sunscreens to achieve highest SPF
that SPF value decreases with inadequate application. This and water resistance. Generally, sunscreens labelled as water
suggests that a high-SPF sunscreen, such as greater than 50, resistant with higher SPFs are typically W/O emulsions,
is preferred to compensate for the typical insufficient appli- whereas those without water-resistant labelling are typically
cation of sunscreen. O/W emulsions. However, patient preference for a vehicle
with O/W because of its lighter feel and noncomedogenic
Caveats. Despite the various advantages of high-SPF properties can significantly affect use and therefore may take
products, ultrahigh SPF values such as greater than 70 are precedence.
more difficult to measure and reproduce during production. Grade of Recommendation: WEAK
In addition, public misinterpretation of higher SPF values
as the single most important aspect of photoprotection can Should Inorganic or Organic Sunscreens Be Used? Inorganic
lead to a false sense of security. Autier et al showed patients (physical) sunscreens were traditionally thicker and whiter
using SPF 30 sunscreen had increased mean cumulative sun formulations, which were not aesthetically pleasing. In a
exposure and mean duration of sunbathing when compared small study, most people applied only about 65% of the quan-
with the SPF 15 group.31 Recent FDA-proposed changes to tity of inorganic sunscreens compared with organic sun-
the 2011 FDA sunscreen monograph state that the maximum screens. As a result, the measured SPF of inorganic sunscreens
proposed SPF value on sunscreen labels should be SPF 60 was less than half the organic (chemical) ones.35 Since the
or higher, and sunscreens with an SPF value of 15 or higher development of micronized particles, many current micron-
should also be required to provide broad-spectrum protec- ized inorganic sunscreens are much less visible on the skin.36
tion. Although media controversy has risen in recent decades
Recommendation: A broad-spectrum sunscreen with UVA regarding systemic absorption of inorganic micronized par-
as well as UVB filters and SPF of at least 30 should be ticles and its potential harms, studies have failed to demon-
applied, and even-higher SPF sunscreens may be used to strate this proposed harm. An in vitro assessment determined
compensate for common underapplication of sunscreen. that less than 0.03% of a nanoparticulate zinc oxide sun-
Patients should be educated on the importance of proper screen formulation penetrated the uppermost layer of the
application and other important factors affecting effective- stratum corneum (SC), and no particles could be detected in
ness of sunscreen apart from the SPF value. the lower SC. These findings were confirmed by 2 studies
Grade of Recommendation: STRONG conducted under in vivo conditions that demonstrated that
titanium oxide and zinc oxide nanoparticles were absent or
What is the Preferred Vehicle of Sunscreens? The vehicle of their levels were too low to be tested under the SC, thus mak-
sunscreen is critical for its efficacy and uptake in usage. The ing significant penetration toward the underlying keratino-
formulation of a sunscreen is primarily determined by the cytes unlikely.37,38 The safety of sunscreens is further detailed
emulsifier system.4 The Mintel global New Products Data- in the risk-benefit analysis section of this review.
base shows that, worldwide, emulsion products such as Recommendation: A broad-spectrum sunscreen contain-
lotions and creams/gel creams are the most popular.4 Broadly, ing UVA and UVB filters is recommended, regardless of
the emulsion type can be either oil in water (O/W) or water whether the components are organic or inorganic. When
in oil (W/O). In general, the O/W systems are often preferred using sunscreens with primarily nonmicronized inorganic
because of their lighter feel on the skin.21 filters, it is especially more important to educate the patient
Sohn and colleagues studied in vitro application of sun- regarding adequate application amount since evidence shows
screens containing the same filters in different vehicles of underapplication tends to occur.
W/O, O/W cream, O/W spray, gel, and a clear lipo-alcoholic Grade of Recommendation: STRONG
spray. The W/O resulted in significantly higher SPF than all
other formulations. This appears to be due to its more When Should Water-Resistant Sunscreens Be Used? Water-
homogenous and thicker film distribution over the applied resistant labelling of a sunscreen is determined by how well
area.32 W/O emulsions also have a low hydrophilic-lipo- it binds to skin and withstands adverse conditions such as
philic balance and use water-insoluble emulsifiers, making swimming, sweating, friction, and removal through other
them more water-insoluble, thus preventing loss through physical contact.36 Currently, Health Canada’s 2018 primary
6 Journal of Cutaneous Medicine and Surgery 00(0)

sunscreen monograph defines a sunscreen product as either high-SPF products (≥ 30) and reapplication is empirically
water/sweat resistant for 40 or 80 minutes if it retains protec- recommended to compensate for underapplication.
tive properties for 40 minutes and 80 minutes, respectively, Grade of Recommendation: STRONG
following moderate activity in 23°C to 32°C (73°F to 90°F)
indoor fresh water. Furthermore, “waterproof” or “sweat- Expiry Date. The literature search yielded no published
proof” labels are considered misleading and thus should not studies on the effectiveness of sunscreens past the expiry
be used, reflecting the lack of evidence behind claims of pro- date. Thus, it may be logical to recommend use of sun-
longed protection. Stokes and Diffey39 found that nearly all screen only within the expiry date to avoid any potential
the protective effect of non–water-resistant products disap- harm, although this is not supported by any evidence. Most
peared after 20 minutes of water immersion, and there were sunscreen manufacturers also have a recommended period
no significant differences between SPF retention in “water- after opening (POA), which is the maximum duration over
resistant” compared with “waterproof” products. which the consumer may use the product after opening.
Other than water resistance, friction- or rub-resistant prop- Although the POA for many sunscreens is 12 months, the
erties could affect the photoprotective effect of sunscreens as rationale is unclear. A study has shown that expiry dates
well. Stokes and Diffey measured SPF values prior to and relate to the conditions of sunscreen usage, storage, formu-
after agitation with sand and found that even after allowing 20 lation, and form.44 All sunscreens sold in Canada require an
minutes for the sunscreen to dry, 15%-60% of the photopro- expiry date on the label.45
tective effect was lost after contact with the sand.39 When placed in temperatures ranging from −20°C to
Recommendation: Water-resistant sunscreen should be 60°C (−4°F to 140°F) for 8 hours, some sunscreens were
worn in conditions where there is significant sweating, water shown to have phase changes and discolouration at the
immersion, increased skin friction via physical contact, or extremes of temperatures. However, it is unclear whether
contact with sand. Immediate reapplication is necessary to these macroscopic changes observed would decrease sun-
compensate for loss of photoprotective effects after any of screen efficacy.46
these activities. Recommendation: Sunscreens should be stored at room
Grade of Recommendation: STRONG temperature to ensure stability. There is a lack of evidence to
support whether it is safe or unsafe to use sunscreens past the
Lip Protection. Lip protection is an important component of manufacturers’ specified expiry date or recommended PAO.
safe-sun practice. UVR has been well demonstrated as a risk Grade of Recommendation: WEAK
factor for the development of lip cancers.40 UV filters are
available in many commercial products such as lip balm, lip
Sunscreen Application
gloss, and lipstick. Use of photoprotective lip products
among female farmers has been correlated to decreased risk What Amount of Sunscreen Is Appropriate to Apply? The FDA
of lip cancers.41 and international protocols recommend applying 2 mg/cm2 of
There are no specific recommendations regarding SPF sunscreen or 35 mL per application to adequately cover
and application of lip sunscreens from the FDA or Health 1.73 m2, the average adult body surface area.36 This recom-
Canada. When applied to the lip, the SPF value of lipsticks mendation is well supported by numerous studies.29,36,47 In
was on average 1.2 units lower than the label SPF of 16.42 particular, a multicentre study29 found a linear dependence of
Although this margin between in vitro and in vivo lip appli- the SPF on the quantity applied (0.5, 1.0, 2.0 mg/cm2) and
cation is much smaller compared with sunscreen application concluded that 2 mg/cm2 is ideal. However, for the consumer,
on the rest of the body, the authors suggest the practical SPF the 2 mg/cm2 measurement makes little practical sense. Stud-
of lip products must be considered as lower than the manu- ies show that consumers typically apply much less, usually
facturer’s label. between 0.5 and 1.5 mg/cm2.31,48 The most important factor in
Similar to body sunscreens, underapplication of lip sun- the application of sunscreen is to apply a liberal quantity,35
screens also occurs. Maier et al showed an application thick- and this is the wording used in Canada’s updated sun-safety
ness of less than 1 mg/cm2 for lipsticks during laboratory messages.49 In children, Diaz and colleagues found that appli-
conditions. In the field experiment in which participants cation with a controlled device such as a pump or squeeze
applied lipstick according to their own habits while skiing, bottle yielded higher quantity.50 Ou-Yang et al30 found sun-
the thickness increased to 1.58-1.76 mg/cm2. This was attrib- screens with SPF 70 and above may compensate for underap-
uted to increased use in outdoor conditions, where the mois- plication by consumers.
turizing effects of the lipstick encouraged more use. The Recommendation: Sunscreens should be applied liberally
median daily frequency of application was 2.2-3 times.43 to all exposed areas. As a practical estimate to the consumer,
There are no other data to guide frequency of lip-sunscreen approximately 45 ml (the amount of 1 shot glass) would be
application. more than enough to cover the entire body surface of most
Recommendation: Lip-photoprotective products should average-sized individuals, or 2-3 tablespoons for the body
be applied generously to cover the whole lip. The use of and 1-2 teaspoons for the face and neck.45
Li et al 7

Grade of Recommendation: STRONG Grade of Recommendation: STRONG

How Frequently Should Sunscreen Be Reapplied? Does Physical How Long Before Sun Exposure Should Sunscreen Be
Activity Affect the Frequency of Application? Several studies Applied? Several review articles state that sunscreen should
have addressed sunscreen reapplication. Heerfordt showed be applied liberally to exposed sites 15 to 30 minutes prior to
that double sunscreen application optimizes sunscreen use sun exposure.35,36,55 These recommendations are based on
compared with a single application as the median partici- how the sunscreens were tested, as there was a complete lack
pant had applied between 13% and 100% more sunscreen of evidence to support this practice in our literature review.
at the selected skin sites after double application than sin- Sunscreen-testing protocols mandate drying times of 15-20
gle application51. In a study of 30 office workers, where minutes before SPF testing can begin (to ensure water resis-
half were randomly assigned to having SPF 15-30 sun- tance): Mandatory labelling reflects this instruction. There
screen reapplied after 3 hours, no significant difference in are no data to suggest that there is a delay in sunscreen effi-
absorption readings (taken at 20 minutes and then hourly cacy; in fact, a recent study showed sunscreen offered imme-
for 1-6 hours after initial application) was found in the diate protection when applied.56
reapplication group52. Similar findings in a split-face Recommendation: Sunscreen should be applied prior to
design study by Rigel et al.24 found no difference in ery- sun exposure. It would be reasonable to wait 15-30 minutes
thema with reapplication 2 hours after UV exposure in after application of sunscreen before water exposure to
golfers. Bodekaer et al53 studied the persistence of sun- ensure water resistance.
screens during physical activity, hot environment, and Grade of Recommendation: WEAK
bathing during an 8-hour period and concluded that one
application is sufficient to reduce erythema caused by Does Application of Sunscreen Vary for Different Skin
UVB, although this is assuming the recommended formu- Types? Although skin cancer accounts for only 1%-2% of all
lation and amount is applied. neoplasms in African Americans and 2%-4% in Asian Amer-
To test the recommendation made by many public health icans as compared with 20%-30% of Caucasians, there is a
agencies to reapply sunscreen every 2-3 hours, Diffey and higher morbidity and mortality in individuals of colour as
Grice35 derived a mathematical model to determine how sev- their diagnoses and treatments are often delayed.36 The aver-
eral factors, including the time of sunscreen reapplication, age SPF of black skin is 13.4 as compared with white skin,
influence photoprotection. The resultant recommendation is which is 3.4.57
reapplying to exposed sites 15-30 minutes after sun exposure A cross-sectional study using the American Cancer
begins and after vigorous activity that could remove sun- Society’s sun surveys I and II, a randomized, telephone-
screen, such as swimming, toweling, and excessive sweat- based, nationally representative survey of the US population
ing/rubbing. Reapplying sunscreen during sun exposure is of teens age 11-18 years (n = 1187 in 1998; n = 1931 in
useful to compensate for initial underapplication and replac- 2004)58 found there was a significant difference between
ing sunscreen that may have been removed by water, friction, Caucasians and non-Caucasians or Hispanic individuals in
and/or sweat. Interestingly, SPF 30 sunscreens have been their knowledge of the risks of UVR causing cancer and the
shown to accumulate in the skin when applied 3 times daily, importance of photoprotection including sunscreen.
providing a higher SPF.53 More research is needed to support However, the cosmetic appearance of a tan was significantly
these findings, however. less desirable for non-Caucasians or Hispanics than
An important consideration when applying sunscreen Caucasians.
during physical activity is the effect of sweating on sun- A cross-sectional study of African American patients
screen protection and vice versa. A controlled, randomized, (n = 55) attending a primary care medical clinic for dermato-
split-face and split-arm clinical study with 24 female partici- logical concerns found 74% of respondents had never used
pants conducted by Ou-Yang et al54 found no significant dif- sunscreen and that only 15% sunscreen users and 11% non-
ferences in either skin temperatures or sweat rates between sunscreen users had ever been counselled to wear sunscreen
the treated (application of sweat-resistant sunscreen) and by either a parent or a medical professional59. In contrast,
untreated control skin sites during exercise. As sweating is a 23% of sunscreen users had experienced a sunburn vs 11% of
crucial process in skin cooling and thermal regulation, this nonusers had experienced a sunburn, and the majority of all
study highlights the safety of using water- or sweat-resistant respondents (62% of sunscreen users and 73% of nonsun-
sunscreen during exercise. screen users) were unaware that African Americans could get
Recommendation: If the appropriate amount of sunscreen skin cancer59.
is initially applied, reapplication is necessary only after A cross-sectional study using the dermatology section of
activities that may remove the sunscreen layer, such as swim- 2003-2006 National Health and Nutrition Examination
ming, sweating, and friction. There is no clear evidence to Survey found that African Americans were 86% less likely
suggest a specific frequency of reapplication in the absence than Caucasians to wear sunscreen, and Mexican Americans
of these activities within an 8-hour period. were 25% less likely to wear sunscreen than Caucasians. Of
8 Journal of Cutaneous Medicine and Surgery 00(0)

all the participants who reported having a severe sunburn, longer time to pregnancy. In another study by Janjua66,
African Americans had a 7-fold lower likelihood of wearing although oxybenzone (also known as BP-3) and octinoxate
sunscreen than their white counterparts.4 were systemically absorbed after 1 week’s application, no
Currently, there are no studies that assess the absolute risk significant change in reproductive hormone levels was
reduction of sunscreen use and skin cancer in people of detected. However, a recent systematic review67 suggests
colour (African, Asian, or Latino descent). There is a need to exposure to BP-3 is statistically associated with reproduc-
quantify this risk reduction as 1 in 5 Canadians identified as tive toxicity in humans and animals, but the clinical signifi-
visible minorities in 201160. cance is unclear. In human studies, high levels of BP-3
Recommendation: People of colour tend to underuse pho- exposure were shown to be linked to an increase in male
toprotection, including sunscreen. More data are needed to birth weight but a decline in female birth weight and male
understand the risk reduction provided by sunscreen, beyond gestational age, but not other reproductive outcomes, includ-
just sunburn. ing semen motility, female fecundity, male idiopathic infer-
Grade of Recommendation: WEAK tility, spontaneous abortion, male genital abnormalities, and
reproductive hormone levels. Animal studies, however,
demonstrated negative reproductive outcomes including
Risk-Benefit Analysis decreased egg production, hatching, testosterone, and epi-
Is Sunscreen Harmful (ie, Risks of Compounds/Ingredients)? didymal sperm density as well as prolonged estrous cycles.
There has been lots of media attention surrounding the poten- The prevalence of total exposure to BP-3 by the general
tial harmful health effects of sunscreen. Recently the FDA public is high, as phenolic compounds like BP-3 are preva-
issued a new amendment to its sunscreen monograph and lent in the air, drinking water, food, and personal care prod-
changes to its designation of ingredients labelled as “gener- ucts.68 Although the safety threshold of BP-3 exposure is
ally recognized as safe and effective” (GRASE). Although unclear, studies report a systematic absorption of BP-3 in
there are no urgent safety concerns, more safety and efficacy humans at a rate of up to 2% after dermal application.
data on 12 organic (chemical) sunscreen ingredients (cinox- Oxybenzone is used in a variety of other products, such as
ate, dioxybenzone, ensulizole, homosalate, meradimate, plastics as a photostabilizer, and cosmetic products, includ-
octinoxate, octisalate, octocrylene, padimate O, sulisoben- ing shampoo, cream, lotion, hairspray, nail polish, and per-
zone, oxybenzone, and avobenzone) are required before sun- fume. Overall, no consensus appears to exist regarding the
screens with those ingredients can be labelled as GRASE. estrogenic and antiandrogenic activity of UV filters and the
These compounds have not been deemed unsafe, but it is felt clinical relevance remains uncertain.
more information is needed. Currently, the inorganic (physi- In addition, environmental concerns about some UV fil-
cal) filters titanium dioxide and zinc oxide are considered ters have been raised. An in vitro study demonstrated that
GRASE for use in sunscreens, whereas PABA and trolamine BP-3 may pose a hazard to coral reefs and their resiliency to
salicylate are not GRASE because of safety issues. climate change as it produces morphological deformities,
As mentioned in the inorganic vs. organic section above, damages their DNA, and acts as an endocrine disruptor.69
concerns regarding the potential systemic absorption of Similarly, a review showed that BP-3 may be a contributor to
nanoparticles found in physical sunscreen formulations have coral reef bleaching, although the role of warming ocean
been alleviated by studies showing lack of absorption temperatures and pollutants is a strong confounder.70
through the stratum corneum.37,38 Furthermore, they found the presence of organic UV filters
Components in chemical sunscreens have been impli- in almost all water sources and various fish species world-
cated in photoallergic contact dermatitis, particularly benzo- wide, and that these UV filters are not easily removed by
phenone-3, octyl methoxycinnamate, and octocrylene.61,62 common wastewater treatment-plant technique. The current
Similarly, a review found that although allergy to sunscreen concentration these agents in the water is not at a toxic level
represents a small proportion (<1%) of allergic contact der- for coral reefs, but these important signals require further
matitis reactions in North America, it is one of the most com- study, as these concentrations may rise in the future with
mon causes of photoallergy63. On the other hand, a BP-3 and other filters in so many daily-use products.
meta-analysis64 of 64 exaggerated-use studies found that Recommendation: There are no definitive data to support
sunscreen products formulated with 1%-6% oxybenzone do that sunscreen filters cause any toxicity in humans. There are
not possess a significant sensitization or irritation potential some signals that there is a need for further study on the
for the general public and that the incidence rate is actually effect of certain UV filters on the environment. The SC
overestimated in the literature. appears to be an effective barrier against the penetration of
Concern has also been raised regarding benzophenone inorganic zinc and titanium dioxide nanoparticulates; there-
UVR filters and their reported estrogenic and antiandro- fore, significant systemic absorption should not be a concern.
genic activity. A prospective cohort study65 found that male The most common adverse effect of using chemical sun-
exposure to select UV filters (BP-2 and 4-hydroxybenzo- screens is the risk of photoallergy, and overall the prevalence
phenone) may diminish couples’ fecundity, resulting in a is quite low. There is currently a lack of evidence to suggest
Li et al 9

sunscreens containing benzophenone filters lead to decreased photoaging, including rhytides, pigmentary changes, and
fertility. Although a recent laboratory study suggests oxyben- telangiectasias.
zone may pose a hazard to coral, more research is needed, From biopsy-specimen analysis, Phillips and colleagues
particularly because a direct association between sunscreen concluded that daily use of sunscreen reduces UV exposure-
posing a threat has not been established, especially given its related skin damage compared with intermittent use of equal
abundance in various other products. or higher SPF products.73 Similarly, Seité demonstrated that
Grade of Recommendation: STRONG daily moisturizers with broad-spectrum sunscreen protected
against solar UV-induced skin damages in the epidermis and
Are Sunscreens Safe for Infants? Health Canada recommends dermis and daily application prevents UVA radiation-induced
sunscreen use for children older than age 6 months and to transcriptional expression of genes that are directly linked to
consult a health care practitioner regarding its use in younger skin aging and also reflect the skin’s antioxidative stress
children (Health Canada 2015). Avoidance of sun and pro- defense response.74
tective clothing are the mainstay for sun safety in infants A photostable sunscreen with SPF 55 and high UVA pro-
younger than age 6 months. The CDA, the Canadian Pediat- tective factor provided proportionately high protection
rics Society (CPS), and the American Academy of Pediatrics against multiple cellular damage markers known to contrib-
(AAP) state that sunscreen can be applied to small areas that ute to photoaging.75 Meinke et al found that sunscreens even
clothing cannot cover such as the face or back of the hands offer protection in the infrared spectrum, which, as in the
(CDA 2016, CPS 2011, AAP 2015), but should be washed UV-wavelength range, also generates free radicals, contrib-
off when sun protection is no longer needed. The CDA and uting to photoaging.76
the CPS recommend using a sunscreen with an SPF of 30, Hughes et al77 published the results of a pivotal randomized
whereas the AAP recommends sunscreen with an SPF of 15 controlled trial. A total of 903 adult Australians were random-
or greater. There are no studies that directly evaluate the ized to daily use or discretionary use of sunscreen (control).
safety of sunscreens in infants younger than age 6 months. The daily sunscreen group showed no detectable increase in
Young infants have a higher body surface-to-mass ratio and skin aging after 4.5 years; skin aging from baseline to the end
absorptive area in combination with their underdeveloped of the trial was 24% less in the daily sunscreen group than in
skin, including a thinner SC and epidermal thickness and the discretionary sunscreen group. In fact, a systematic review
lower lipid-to-protein ratio, allowing for more sunscreen to of randomized controlled trials shows that evidence, though
be potentially absorbed.71 In particular, newer sunscreens limited, supports beneficial effects of sunscreen application on
contain nanoparticles, and this risk has not been quantified photoaging.78 Similarly, another review of clinical trials dem-
for infants who have thinner SCs than adults.37 A cohort onstrates that sunscreens containing Ecamsule (Mexoryl SX),
study of 54 pairs of mothers and babies found UV filters a widely used chemical sunscreen filter, prevent the impact of
were present in 85% of breast milk samples, only 55% of UVA on skin photodamage.79
women reporting using sunscreens72, suggesting that some Recommendation: There is strong evidence in the litera-
women are exposed to UV filters in their other cosmetic ture, including results from randomized controlled trials, that
products or there is potentially recall bias. The health impli- sunscreen prevents photoaging.
cation of these UV filters in breast milk requires further Grade of Recommendation: STRONG
elucidation.
Recommendation: There is a lack of evidence examining Does Sunscreen Prevent Skin Cancer? A randomized con-
the pharmacokinetics of sunscreens in young infants that trolled trial of adult Australians80 found that after prolonged
contributes to recommendations based largely on theoretical follow-up, squamous cell carcinoma tumour rates were
harm vs empirical data. Clinical trials in this vulnerable age decreased by almost 40% in people randomized to daily
group are very difficult to design to meet today’s ethical stan- sunscreen use compared with those with discretionary use.
dards. It is reasonable given the paucity of evidence to con- Basal cell carcinoma tumour rates tended to decrease as
tinue to limit the use of sunscreen in children younger than well, but not significantly. Another randomized controlled
age 6 months as physiologically their skin is immature and trial found daily use of sunscreen prevents and/or retards the
there are theoretically potential risks of nanoparticles and development of solar keratoses among adults.81 Moreover,
UV filters being absorbed. Photoprotection should be based regular use of sunscreen has been shown to be cost effective
largely on behavioural modification in this group, such as in NMSC and actinic keratosis prevention.82 Ten years after
avoiding peak UV hours, seeking shade, and using protective the Australian randomized controlled trial cessation, 11 new
clothing. primary melanomas were identified in the daily sunscreen
Grade of Recommendation: WEAK group and 22 in the discretionary group, showing that mela-
noma may also be preventable by regular sunscreen use in
Does Sunscreen Prevent Skin Damage/Aging/Wrinkles? Cumu- adults.83
lative UV exposure is a major contributing factor in aging Conflicting data presented in a systematic review and
skin. Regular use of sunscreen protects against signs of meta-analysis84 showed no association between sunscreen
10 Journal of Cutaneous Medicine and Surgery 00(0)

use and risk of melanoma and NMSC in the general popula- and the potential environmental and reproductive toxicity of
tion. However, this review, which included 28 observational sunscreens are supported by weak evidence because of the
studies and only 1 community-based randomized trial, had limited number of studies. Second, this review included
major limitations. First, many of the included case-control studies published only in English, which presents language
trials used primarily UVB sunscreens rather than broad- bias and may limit the analysis of some research questions.
spectrum filters. Second, only 5 of the included studies The inclusion of non-English studies may allow for a greater
addressed NMSC. Although it is plausible that the benefit of ability to answer some research questions or to further
sunscreen use in melanoma development may vary, because increase the strength of some recommendations presented in
of its multifactorial nature, which includes multiple genetic this review. Despite these limitations, the existing body of
factors, squamous and basal cell carcinoma have been shown evidence suggests sunscreen is one of the best-supported
to be more strongly linked to sun exposure.85 Third, there photodamage-prevention options, especially given the rela-
was a low quality of evidence overall due to inconsistencies tively high risk of photodamage and skin cancer associated
among included studies and its retrospective design. Rueegg with UV exposure.
et al found heterogeneous summary estimates for the sun- This in-depth review consolidates the available evidence
screen-melanoma association from observational studies but supporting sun-protection guidelines. The 2016 National
a protective effect of sunscreen against skin cancer in the Consensus study on the Recommended Core Content for Sun
only randomized controlled trial performed.86 Safety Messaging for public education in Canada was the
Recommendation: Regular sunscreen use can prevent most recent up-to-date source of information for clinicians
melanoma and NMSC. The literature that suggests there is since its last update in 1945. This current review adds more
no effect of sunscreen on the development of skin cancer is up-to-date information and an in-depth analysis of the evi-
flawed in that it does not take well-established skin cancer dence to the 2016 consensus study. Clinicians should be
risk factors into account. aware of the strength of evidence when making routine rec-
Grade of Recommendation: STRONG ommendations on sunscreen use. This is particularly impor-
tant when considering that skin cancer is the most common
cancer in Canada and is largely preventable.3
Discussion
Sunscreens are widely used; however, some widely pro- Conclusion
moted sun-safety messages do not reflect current evidence.
In this review, we have evaluated and discussed the strength Our review revealed that the level of evidence supporting
of recommendations relating to the efficacy of physical bar- recommendations for the use of sunscreens and other sun-
riers, sunscreen properties and application, and risk-benefit protection methods varies from fair to good, as assessed
analysis. using the CTFPHC’s GRADE system. Our updated recom-
Our review of 18 years of literature yielded an overall mendations, derived from a critical appraisal of the literature,
lack of high-quality evidence. A total of 84 studies were are a useful educational tool for the practicing dermatologist
included in this review addressing 16 questions that in counselling patients about sun safety.
described the physical barriers, sunscreen properties and
application, and risk-benefit analysis. There is strong evi- Declaration of Conflicting Interests
dence supporting the use of a broad-spectrum UVA and The authors declared no potential conflicts of interest with respect
UVB sunscreen with a minimum SPF of 30, applied liber- to the research, authorship, and/or publication of this article.
ally to all exposure areas including the lips. Higher SPF is
recommended, reapplication may be considered to compen- Funding
sate for underapplication but is not mandatory, and water- The authors received no financial support for the research, author-
resistant sunscreen is recommended for physical activity. ship, and/or publication of this article.
There is strong evidence supporting the safety profile of
sunscreens and their efficacy in photoaging and melanoma Supplemental Material
and NMSC prevention. Supplemental material for this article is available online.
There are several limitations to this review. First, the rec-
ommendations that were graded as weak had a high degree ORCID iD
of heterogeneity or limited data in the existing evidence.
Heidi Li [Link]
There was weak evidence supporting the use of photopro-
tection in children younger than age 6 months, although the
evidence is expected to be inherently weaker as there is a References
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 International Journal of Applied Pharmaceutics

ISSN- 0975-7058 Vol 10, Issue 6, 2018

Review Article

SUNSCREENS: DEVELOPMENTS AND CHALLENGES

P. SWATHI REDDY1, AISHWARYA SURESHKUMAR1, VIKAS JAIN1*

1Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru 570015, India
Email: vikasjain@[Link]
Received: 21 Feb 2018, Revised and Accepted: 04 Sep 2018
ABSTRACT
One of the major concerns affecting the human skin is the exposure to ultra-violet radiations (UVR) causing photo-damage and skin cancers. In
order to provide preventive measures against such incidences, there is an increased demand for sun-protectants. Sun screening agents have shown
beneficiary effects on the skin by reducing the exposure of UVR and its associated symptoms. Although various constituents have been recognized to
have sun protecting activity, their safety and efficacy is still a concern. The United States Food and Drugs Administration (USFDA) and European
Guidelines (EU) guidelines have made the sun protecting factor (SPF) and other such indices compulsory on the labels of such formulas to guide the
consumers for better selection. The various ranges of radiations and skin types influence the mechanism of photoreaction and subsequent choice of
the formulation. Apart from existing agents, certain novel sun-screening agents and technologies are now available to provide better protection to
human populations.
Keywords: Sun protection, UVA and UVB, Sunscreen agents, COLIPA
© 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license ([Link]
DOI: [Link]

INTRODUCTION
The body, in general, undergoes ageing with time. On a molecular
level, several intrinsic and extrinsic factors trigger ageing resulting
in malfunctioning of various activities in the body. These result in
the cutaneous changes associated with ageing. Intrinsic ageing is due
to the natural ageing process of the body which may be genetic in
nature affected by hormonal and vascular changes. When intrinsic
changes get accelerated due to environmental conditions,
significantly due to over-exposure to UVR, it results in the extrinsic
photo-ageing [1].
If the skin is exposed to the harmful UVR for a long period of time, it
may result in severe damage to the skin by producing free radicals,
DNA breakdown, etc. causing sunburn, pigmentation, wrinkles,
dermatitis, urticaria, ageing, immune-suppression and ultimately skin
cancer [2-4]. Therefore, although complete avoidance of the solar Fig. 1: Melanin synthesis [12]
radiations is not possible and not advisable, the exposure needs to be
balanced for preventing the skin from the deleterious effects of the
rays [5, 6]. Sunscreens and UV filters have proved to be an excellent
choice over the years [7-9]. This review incorporates search criteria
based on the keywords mentioned in the manuscript and articles from
major scientific resources like scopus, pubmed, science direct and
google scholar were cited. The articles up to the year 2018 have been
referred, but certain very old articles were also brought into use for
demonstrating the historical importance of the facts.
The human skin
The skin is a complex and the largest organ in the human body with a
surface area of about 2m2 covered with wrinkles, lines, dents, furrows
etc [1, 10]. The thickness of the skin varies from part to part depending
upon the function of the part it is covering. The major functions of the
skin are protection, communication, and control. There are three distinct
layers of the skin-the epidermis, dermis and the hypodermis/
subcutaneous layer. Apart from the different layers, there are various
cells which are associated with the production of melanin (melanocytes)
and cells associated with defence (Langerhans’ cells) [11]. Fig. 2: Penetration of UV rays into the skin [17]
Melanogenesis
Penetration capacity and effects of UVR on skin
The melanocytes produce the pigment melanin which is responsible
for the colour of the skin, eyes, and hair. During the process of When the skin is exposed to the solar radiation, these interact with
keratinisation, melanin is transferred to the keratinocytes. The main the biological molecules causing temporary/permanent changes in
function of the melanin is to protect the skin from the UVR. The the molecules. There are several chromophores (molecules capable
melanin pigment is classified into two types, particularly into of absorbing light) in the layers of the skin, and this absorption leads
Eumelanin and Pheomelanin [12]. The schematic representation of to photo-damage. The solar radiations affecting the skin are widely
melanin synthesis has been depicted in fig. 1. divided into UVR (UVA, UVB) and visible light.
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UVB radiations (280-320 nm) affect the basal layer of the epidermis a certain time of the day is also considered as a measure to protect
and the upper margin of the dermis. These radiations are absorbed the skin from the UVR. In spite of all these, sunscreens are the most
by the chromophores present in the proliferating cells of the preferred and predominant sun protectant due to its ease of
epidermis, mainly the DNA causing sunburn. application and higher efficacy of protection.
UVA radiations (320-400 nm) have a deeper penetration capacity than Sunscreens
UVB. These radiations penetrate to the dermal layer and interact with
collagen and elastin, which are considered to be the structural Sunscreens act by preventing and blocking the damaging effects of
components of the skin (fig. 2). These photochemical reactions cause UVR of sunlight. These are generally applied over the skin which is
premature ageing of the skin resulting in the formation of wrinkles exposed to the sun primarily to absorb or scatter the rays before it
and loss of elasticity. These radiations also cause immediate tanning of penetrates into the body. These cause damage to the integrity of the
the skin due to excess release of melanin [13]. cells causing premature ageing of the skin which can be associated
with sagging, wrinkling, pigmentation, hyperplasia, etc. Sunscreens
Mechanism of photoreaction to an extent have controlled the deleterious effects of the UVR.
Exposure to UVR has various deleterious effects on the skin. The Ideal properties of sunscreens
acute effects of UVR include inflammation induction. Cytokines and
various mediators in the skin are induced by UVB that causes There are various characteristics which are required by the
sunburn [14]. In response to sunburn, causing cell injury, several sunscreens to categorize as the ideal sunscreen. Since these agents are
damage response pathways are induced in the keratinocytes such as both complex organic and inorganic in nature, the biodegradability of
p53 activation, DNA repair activation or apoptosis induction if the these molecules needs to be noted as it may pose a threat to the
damage is severe [15]. This causes proliferation of keratinocytes environment in which it is synthesized and formulated.
mediated by epidermal growth factors which result in an up-
An ideal sunscreen must absorb the rays causing sunburn, typically
regulation and building up of melanin pigment on the skin.
in the range of 2900-3300 A ° and be stable in the presence of
Although UVA and UV B are potent mediators for carcinogenesis; sunlight to which it is expected to show its efficacy. If the molecule is
they cause damage to the skin through different pathways [16]. UV B not stable and gets degraded, the by-product should have an
stimulates inflammation and formation of photolesions whereas UV absorption capacity of 2900-3300 A °. The decomposed products
A stimulates damage to DNA and other macromolecules [17]. should not be toxic and irritating. It should be neutral in nature and
Various reactive oxidative species are formed due to mutation- should not be affected by the presence of an acid or a base and also
initiated by UVA [18]. should have a good solubility in the ointment base in which it is
formulated and should not be easily washed away with water or
There are several cellular maintenance pathways to inactivate during perspiration. A non-volatile agent will be ideal so that
oxidative species and repair DNA damage [19]. Cells have a complex evaporation does not take place during application.
inbuilt network of anti-oxidant molecules which inactivate ROS to
prevent damage to DNA and other macromolecules. Glutathione (GSH) Although all the ideal characteristics cannot be obtained from a
is an antioxidant composed of three amino acids–cysteine, glycine, and single agent, a combination of sunscreen agents are used together to
glutamine. GSH acts as a reducing agent by donating an electron to the formulate a sunscreen formulation.
ROS to neutralize their activity. GSH, in turn, gets oxidised which can
be reduced to the ground state by GSH reductase. Catalase, another Classification of sunscreen agents
anti-oxidant which inactivates Hydrogen Peroxide and Superoxide Sunscreen agents can be broadly classified based on their capacity to
Dismutase’s (SODs) inactivates superoxide anions [20]. absorb, scatter or reflect sunlight. High energy UVR is absorbed by
Sun protectants chemical sunscreens while physical sunscreens scatter and reflect the
rays [21]. Chemical agents can be organic compounds, and a
There are various kinds of physical sun protectants like protective combination of organic and inorganic compounds can be incorporated
clothing, sunglasses, hats, and an umbrella. Avoiding sunlight during into a formulation for obtaining broad spectrum formulation (fig. 3).

Fig. 3: Classification of sunscreen agents [21]

Mechanism of action particles in the upper skin layers which may enhance the
efficiency of the sunscreen compound thereby increasing the sun
The mechanism of action of various sunscreens can be protection factor [22]. The use of certain sunscreens causes a
understood by the type of molecule incorporated into the reduction in the generation of free radicals in the skin due to its
formulation. Inorganic agents act by scattering the micro- antioxidant activity [23].

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Organic molecules, on the other hand, absorb the radiations instead 16 to 24 h after exposure) in sunscreen-protected skin to the time
of scattering them. Thus, this distinct feature makes them the target required in unprotected skin [24-26].
for degradation in the presence of sunlight and therefore these
molecules can lead to the generation of free radicals. Organic The UV-dose/time is used to calculate the SPF using:
sunscreens also have the ability to cause photo-irritation and MED protected skin
photosensitizing reactions. SPF =
MED unprotected skin
Inorganic molecules also have certain disadvantages due to their MED protected skin-minimum erythemal dose for protected skin
dispersion nature of the molecules which require an additional after application of 2 mg/cm2 or 2ul/cm2 of the final formulation of
requirement of surface coating the molecule. This, in turn, reduces the sunscreen product MED unprotected skin-minimum erythemal
the photoreaction of the molecules upon exposure to UVR thus free dose for unprotected skin, i.e. Skin with no sunscreen
radical generation does not take place.
Another factor by which the efficacy of the sunscreen is measured is
Factors determining the efficacy of sunscreens by the Persistent Pigment Darkening (PPD) Protection Factor. One of
1. SPF the major disadvantages of this method is that it is not applicable to
skin type 1 (table 1) and its clinical significance is not clear [27].
2. Substantivity
Immediate pigment darkening response is calculated as the dose of
The sun protection factor is a number representing the ratio of the UVA required to produce the effect with the sun screening agent to
time required for a given irradiation to produce minimal perceptible that produced without an agent [28]. In this method, the clinical
erythema (MED: minimum erythemal dose, the UVR dose necessary significance is unknown, the results obtained are not accurately
to produce the minimal sunburn or minimal perceptible erythema reproducible. This method is applicable to skin types 3 and 4 [29].

Table 1: Classification of skin types based on the degree of tanning

Skin type Hair Eye Response to solar rays References
White, very fair Red, blond Blue Always burns never tan 11
White, very fair Red, blond Blue, green, hazel Usually burns, tans with difficulty 11
Cream white Not particular Not particular Mild burn gradually tans 11
Brown Not particular Not particular Rarely burns, tans with ease 11
Dark brown Not particular Not particular Very rarely burns, tans easily 11
Black Not particular Not particular Never burns, tans easily 11

Formulation aspects biodegradability. It may also cause potential vitamin D3 deficiency

on prolonged use. Also, TiO2 is also categorized as a potential
Although the idea of formulating a sunscreen seem pretty simple, carcinogen. According to studies, it has been observed that ultrafine
with the concept of selecting two or more suitable sunscreen agents particle dust of TiO2 causes respiratory tract cancer as manpower is
and incorporating them in a vehicle base which when applied majorly exposed to these dust during the manufacturing of these
topically will obstruct the UVR before causing damage to the skin, ultrafine molecules. Ultrafine ZnO comparatively is safer to use.
the formulation of sunscreen, in itself, is a big challenge–starting
from selection of an appropriate agent, its compatibility with the Regulatory bodies
vehicle base and other additives, its stability under prescribed
conditions of storage and also on exposure to sunlight and its Several guidelines have come into play due to the ever-increasing
efficacy and efficiency is a big challenge. Thus sunscreen formulation number of sunscreen agents in the recent past. These regulations are
takes a lot of research and understanding of the components used to maintain and monitor the quality along with safety and toxicity
for obtaining a better and effective formula [30]. profile of the sunscreen molecules both in regards to the human and
environmental aspects, the main aim being providing adequate
The most commonly used sunscreen agents are the inorganic, protection against the harmful UVR.
physical agents such as TiO 2 [31] and ZnO. These are widely used
because of lower penetration capacity into the skin, a scattering of USFDA guidelines
the UVR, reduced skin irritation and sensitivity and they provide a Earlier, the FDA had specified rules for the molecules protecting the
broad spectrum of protection in combination [32]. Nanoparticles skin against the UV B radiations. When research and development
(NPs), less than 100 nm are more often used than micronized form took place for molecules protection against UV B, more rules and
(0.1-10 um) of these molecules because NPs provide lower opacity regulations were put forth for providing the completely monitored
without reducing their efficacy [33]. production and release of sunscreen molecules [37].
There are several sunscreen products which contain NPs of titanium When misguiding and false statements started prefacing the market,
dioxide (TiO₂) and zinc oxide (ZnO) or a combination of both. These
US FDA revised to more stringent guidelines thus preventing the use
provide a broad spectrum against UVR along with a transparent
of claims such as ‘broad spectrum’, ‘water and sweat proof’, ‘water
product. The products containing NPs have better texture,
resistant’ without proper investigation and test reports. Therefore,
spreadability and increased UVR protection [34]. There are several
products claiming broad spectrum has to provide adequate
factors which affect the efficiency of NPs such as NP size, NP coating
documents proving its effect against UVA and UV B radiations. A
and the vehicle base in which the NPs are suspended and applied on
the skin. A general formulation strategy is to coat the NP in a product indicating ‘water resistant’ on its label should provide its
silicone-based material. ZnO which is uncoated, are amphiphilic in duration of action [38].
nature and are generally incorporated into the aqueous phase of the Any claim which suggests immediate sun protection or sun
formulation. But, the silicone coated ZnO NPs are hydrophobic in protection prevailing for longer than two hours should not be
nature; thus incorporated into the oil phase of the base. This causes mentioned without directing reapplication. Supporting documents
increased retention of the product during sweating or any other need to be provided to FDA for approval in case any statement
physical activity [35]. TiO2 and ZnO both behave complimentarily which suggests any of the above claims.
when used in combination. TiO2 obstructs UV-Blight while ZnO
obstructs UVA light, thus in combination, they provide the ultimate Drug fact is an integral part of the product label. SPF value is of
broad-spectrum protection [36]. However, NPs does have some utmost importance for sunscreen agents as it decides the category of
demerits regarding environment as it poses a threat due to poor the sunscreen to be used for maximum and effective protection.

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EU guidelines property. Formulations of varying concentrations of extracts were

formulated and evaluated for significant SPF. After evaluation, it was
EU also provides a minimum level of protection against UVA in terms found to be of greater than 6 which show that it can be used as a
of SPF. PPD (in vivo) or COLIPA (in vitro) are the measures by which sunscreen agent [45].
UVA protection is measured, and it must be at least one-third of the
SPF (in vivo) value. As per the guidelines, products are divided into Mineral sources and vitamins
low, medium, high and very high according to the SPF of the products
ranging from SPF 6 to SPF 50+. Star system is also employed for Minerals have been identified as an excellent source of protection
consumer understanding and ease which denotes that 1 has least sun against harmful sun radiations. Some minerals are an integral part of
protection and 5 has the ultra-sun protection [39, 40]. the body for functioning in several roles, especially as biocatalysts.
One of the most important minerals under observation is
Other countries guidelines magnesium. Magnesium is abundantly found in various fruits, nuts
and vegetables like spinach, peanuts, pumpkin, banana, etc. In the
Other countries such as Japan, Australia [41] and New Zealand have body, magnesium is found in the bones, muscles, and brain and acts
similar guidelines though some of the regulations may differ. as a catalyst for many enzymatic reactions in the body. One major
Statements claiming drug facts without proper documents are factor affecting magnesium absorption is vitamin D production.
prohibited as it may mislead the consumers. Vitamin D production is enhanced by sun exposure which in turn
Indian guidelines increases Magnesium absorption. This magnesium is responsible for
protecting the skin against solar radiations by strengthening the
There are only two combination approved products as per the epidermis, accelerating healing of the outer layer of the skin.
Official website of Industrial Regulatory Agency due to lack of
guidelines in the standardization of sunscreen agents and approved Vitamins also play an important role in protecting the skin. These
ingredient list. The products available are a combination of vitamins have anti-oxidant properties which are rich in leafy
octinoxate+avobenzone+oxybenzone+octocrylene+zinc oxide lotion vegetables, cod liver oil, raspberry seed oil, etc. Vitamin A and beta-
and cinoxate+avobenzone+oxybenzone+titanium ioxide lotion. carotene in carrot have an anti-oxidant and anti-inflammatory
Several others sunscreening agents are widely used such as camphor activity that shield the skin from generating free radicals. Raspberry
derivatives and UV broad spectrum active agents. seed oil has the capacity to protect the skin against both UVA and UV
B. This has shown equivalent efficacy to that of titanium dioxide
New developments in sunscreens which is the most widely used sunscreen agent in the market. It is
known to protect the skin from inflammation and pain from
New molecules with broad spectrum efficiency are being identified
sunburn.
from various biological sources like herbs, minerals and various oils
from fish, etc. These chemicals constituents are responsible for their Hydroxyapatite is a mineral present in the bones and teeth of the
activity against solar radiations because of their anti-oxidant human body, present in various forms by substituting the hydroxyl
property to deactivate the free radical generation. These agents have group of the molecule. These form 70% of the bone structure. It can
shown greater and better protection against the radiations when combine with several monovalent and divalent ions like fluoride,
compared to the synthetic molecules as these are bio-degradable chloride, carbonates, calcium, etc. to form various crystalline
causing less harm to the health and the environment. structures of the molecule [46]. Pharmacologically, it is found to
have photoprotective properties as, when evaluated against a
Herbal formulations
placebo, it showed a significant increase in the SPF of the
Herbs have been in the dictionary of treating ailments from centuries. formulation. It has the capacity to block broad spectrum UVR when a
They have known to contain certain phytoconstituents which relieve combination of an ascorbic acid with hydroxyapatites was prepared
many diseases without causing adverse reactions as compared to [47, 48]. When measured against TiO2 it showed as equivalent sun
synthetic molecules. Many molecules from natural sources have screening activity thus proving hydroxyapatites to be a competent
shown good photo-protecting efficacy, like anti-oxidants, due to which physical photoprotective agent [49, 50].
formulations are being made from these sources.
Challenges in formulating sunscreen agents
Turmeric, vitamin E and C, aloe vera, quercetin are some of the
Even though the main aim of formulating an effective sunscreen is to
molecules which have shown great efficacy against harmful UVR.
protect the naked skin against various effects of the sun rays, there
Some of them are discussed in detail below.
are many challenges that regulate the effective use of sunscreen all
Phytoconstituents with photo protectant characteristics over the world. These challenges may be due to the geographical
location, lifestyle diversification, environmental safety concerns and
Quercetin is a molecule obtained from various biological sources also the regulatory authorities controlling and regulating the use of
like wine, apples, and blueberries. It is a flavonoid and has good certain ingredients in the certain cosmetic product due to their
antioxidant and anti-inflammatory properties which are the adverse reactions. Due to these differences, cosmetic sunscreen
prerequisite characteristics required for sunscreen formulations. products are always under the scrutiny of the regulatory bodies
Due to its poor solubility in the aqueous phase, it has lower efficacy regarding their safe use and efficacy; and amidst of all these
when applied topically. Various measures like liposomal controversies, the demand for a better sunscreen is high as it not
formulation, lipid nanocapsules, and smart crystals are taken to only protects the skin from acute skin damages but also from
increase its solubility and thus increase its delivery to the skin. The various high-risk damage like DNA damage resulting in premature
formulations proved to be safe as no toxicity profile is observed. The ageing, wrinkling and ultimately skin cancer [51-53].
liponanocapsules formulations delivered quercetin in optimum
quantity on the surface of the skin which resulted in promising anti- The safety and efficacy of sunscreen agents are because of the fact
inflammatory and free radical scavenging property. Thus, quercetin that most of the sunscreen agents used in the market are synthetic
is a molecule which has the desired property of a competent chemical entities which may be toxic when applied to the skin as it
sunscreen agent [42-43]. gets absorbed into the deeper layers of the skin and cause several
undesired side effects [54]. The increased amount of use of
Moringa oleifera is observed to have various cosmetic advantages sunscreen can also cause a reduction in the formation of vitamin D
along with being a food supplement. The phytoconstituents present due to blockage of UVR penetrating the skin [55-57]. Even though
in Moringa oleifera has been proved to be used as a sun-protecting physical sunscreen agents like TiO2 and ZnO do not penetrate into
agent. The extracts of Moringa oleifera have many photoprotective the skin, the is evidence where these particles, both in nano-
properties along with a significant SPF. Also when formulated, there particulate or non-nano-particulate form have to cause melanoma
were no signs of any significant irritation [44]. formation in mammalian cells [58, 59].

Marcetia taxifolia (ethanolic extract) shows a broad spectrum UVR The solubility of such molecules remains to be yet another challenge
protection as it is rich in flavonoids which have anti-oxidant during formulating a sunscreen product. Some agents are dissolved

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in the oil phase while some are dispersed in the aqueous phase. 17. Klar LR, Almutawa F, Lim HW, Hamzavi I. Effects of ultraviolet
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