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Sun lotion chemicals as endocrine disruptors



Ultraviolet solar radiation is a well-known environmental health risk factor and the use of sun lotions is encouraged to achieve protection mainly from skin cancer. Sun lotions are cosmetic commercial products that combine active and inactive ingredients and many of these are associated with health problems, including allergic reactions and endocrine disorders. This review focuses on their ability to cause endocrine and reproductive impairments, with emphasis laid on the active ingredients (common and less common UV filters). In vitro and in vivo studies have demonstrated their ability to show oestrogenic/anti-oestrogenic and androgenic/anti-androgenic activity. Many ingredients affect the oestrous cycle, spermatogenesis, sexual behaviour, fertility and other reproductive parameters in experimental animals. Their presence in aquatic environments may reveal a new emerging environmental hazard.
Sun lotion chemicals as endocrine disruptors
Sotirios Maipas, Polyxeni Nicolopoulou-Stamati
National and Kapodistrian University of Athens, School of Medicine, First Department of Pathology and Cytology Unit,
1st Pathology Laboratory, Athens, Greece
Both authors contributed equally to this work
Ultraviolet solar radiation is a well-known environmental health risk factor and the use of sun
lotions is encouraged to achieve protection mainly from skin cancer. Sun lotions are cosmetic
commercial products that combine active and inactive ingredients and many of these are
associated with health problems, including allergic reactions and endocrine disorders. This
review focuses on their ability to cause endocrine and reproductive impairments, with empha-
sis laid on the active ingredients (common and less common UV filters). In vitro and in vivo
studies have demonstrated their ability to show oestrogenic/anti-oestrogenic and androgenic/
anti-androgenic activity. Many ingredients affect the oestrous cycle, spermatogenesis, sexual
behaviour, fertility and other reproductive parameters in experimental animals. Their presence
in aquatic environments may reveal a new emerging environmental hazard.
Key words: Active ingredients, Endocrine disruptors, Environmental hazard, Reproductive impair-
ments, Sun creams, Sun lotions, Sunscreens, UV filters
HORMONES 2015, 14(1):32-46
Address for correspondence:
Polyxeni Nicolopoulou-Stamati Professor of Pathology,
Scientific Director of MSc Environment and Health. Capacity
Building for Decision Making, Medical School, National and
Kapodistrian University of Athens, 11527, Greece,
Tel.: +302107462163, Fax:+302106840488,
Received: 16-12-2014, Accepted: 30-01-2015
Ultraviolet (UV) solar radiation is one of the most
studied environmental health risk factors. The Earth’s
atmosphere functions as a natural shield, but it can-
not protect us completely from the UV radiation that
reaches the surface.
Skin has its own protective
mechanisms, such as tanning and stratum thicken-
ing, but the level of photoprotection is insufficient to
prevent the harmful effects of UV radiation.3,4
To achieve a better level of protection, the use of
sun lotions and creams, often with a high protection
factor, is advised.
However, health issues associ-
ated with their ingredients exist and include, among
others, allergic reactions6-8 as well as endocrine and
reproductive disorders.9,10 Manufacturers of sun lotions
constantly modify the composition of their products
(active and inactive ingredients) to make them more
effective and safer for consumers. Nevertheless, the
safety of these products is relative and questionable.
Sun lotions have become popular commercial prod-
ucts. Furthermore, many cosmetic products (not only
sun lotions and creams) are on the market containing
Sun lotion chemicals as endocrine disruptors 33
some of the active ingredients.
Therefore, exposure
to these UV filters does not occur only through tra-
ditional sun protection products. This review article
focuses on the ability of UV filter chemicals to cause
endocrine and/or reproductive impairments.
1.1. UV solar radiation
UV solar radiation is usually divided into three
groups. The most energetic, known as UV-C (100-280
nm), is completely absorbed by atmospheric molecu-
lar oxygen and ozone and does not reach the Earth’s
surface. UV-B (280-315 nm) reaches the surface, its
quantity being determined by stratospheric ozone
concentration since ozone is a strong absorber at
these wavelengths. UV-A (315-400 nm) reaches the
surface without significant losses during its passage
through the atmosphere. Cloudiness impedes both
UV-A and UV-B.
As both UV-B and UV-A cause
negative health effects,
protection from these forms
of radiation is indicated.
To avoid a possible confusion with the spectral
ranges mentioned above, it is useful to redefine them
according to photobiology. Taking into consideration
the biological effects, the spectrum between 200-290
nm is called UV-C and that between 290 and 320 nm
UV-B, while UV-A covers the 320-400 nm range.12
Exposure to UV radiation causes, inter alia, sunburn,
tanning, photoaging, melanoma and other malignan-
cies, cataracts and immunosuppression.
UV-A penetrates more deeply into the skin,
UV-B is
considered to cause more biological effects than UV-
Nevertheless, skin exposure to UV-B is necessary
for the cutaneous synthesis of vitamin D.18
1.2. Sun lotions
Sun lotions are cosmetic products that protect
from UV radiation after topical dermal application
due to their active ingredients. These ingredients
absorb or block UV irradiation by reflection and/
or scattering.19,20 Their properties protect their users
from UV-B or both UV-B and UV-A, depending on
their formulation.
Commercial sun lotions are grouped into three
categories. The first includes those products whose
UV filters are organic chemical absorbers.19,21-23 The
second group includes products which contain metal
oxides (inorganic UV filters, e.g. titanium dioxide and/
or zinc oxide).
The third group includes formula-
tions which combine organic and inorganic agents.
Manufacturers combine different UV filters (here-
inafter referred to as “active ingredients”) to increase
the sun protection factor (SPF) of their lotions or
Simply phrased, SPF is a numerical value
indicating the protection level against sunburn.21
1.3. Endocrine disruptors and reproductive
Endocrine disruptors are chemicals that alter the
normal function of the endocrine system, leading to
a variety of health problems, such as reproductive
impairments and female and male cancers as well.26-29
Exposure to endocrine disruptors starts in utero and
never ceases throughout life, since these chemicals
are present in a variety of daily products, including
food, bottled water and cosmetics.30-35 Some of the
ingredients of sun lotions show endocrine altering
and disrupting properties.9,36,37
Possible reproductive impairments are crucial be-
cause they are associated with infertility.26,27,38-41 The
life of all living organisms is strongly connected with
the environment and reproduction is the key factor
for their survival.42 Endocrine disruptors are omni-
present in ecosystems and some of their properties,
including their bioaccumulation potential, should be
taken seriously into account.43
1.4. Sun lotion chemicals and routes
of exposure
Since sun lotions and creams are applied to the
skin, the main route of exposure to them is dermal. The
skin is the body’s largest organ. It has its own defence
mechanisms such as the formation of a protective
With regard to sun lotions, the effectiveness
of the skin as a barrier against chemicals, biological
agents and radiation depends on many factors such
as the body site of application, the person’s age, the
health status of the skin, the frequency of the appli-
cation, the duration of skin contact with the product
and the possible presence of chemicals that enhance
the penetration of other substances.17,45-47
Furthermore, exposure is also possible through
inhalation. Apart from the fact that some sun lotions
are sprays,
many sun lotions contain fragrances
made with endocrine disruptors.49
Finally, exposure through ingestion is also pos-
sible, especially as a result of hand-to-mouth habit.
Generally, this behaviour is a noteworthy risk factor
for children.51 Additionally, sunscreen lipsticks con-
tribute to the exposure by ingestion.52,53
Since the production of the first sun lotions and
creams, many organic absorbents have been used as
filters. The most common organic chemical absorbers
include the chemicals discussed below.
2.1. Benzophenone compounds
2.1.1. Oxybenzone
Oxybenzone (or 2-hydroxy-4-methoxybenzophe-
none, benzophenone-3, BP3) is a benzophenone (BP)
compound (commonly used as a UV filter) with
known endocrine disrupting characteristics. In vitro
studies (human oestrogen receptor alpha (hERα) and
human androgen receptor (hAR) assays) indicate that
BP3 displays oestrogenic, anti-oestrogenic and anti-
androgenic activity.9
BP3 exhibits anti-oestrogenic and anti-androgenic
activity in vivo in fish. In the brain of adult zebrafish
males, BP3 down-regulates alpha oestrogen receptors
and androgen receptors. The effects mainly occur at an
aquatic concentration of 84 μg/l, but that concentration
is much higher than the highest environmental level
of 10 μg/l, as had been hypothesized by this study.54
Fish exposure to oxybenzone also affects egg produc-
tion and hatching. For instance, exposure of Japanese
medaka to 620 μg/l of BP3 reduces egg production
(temporarily) and the normally expected hatching
percentage. However, effects on these parameters
also occur at lower concentrations (132 μg/l, 16 μg/l).
Significant vitellogenin induction occurs at high doses,
e.g. 620 μg/l in the Japanese medaka (vitellogenin is
a biomarker for oestrogenic results).55,56
Furthermore, oxybenzone increases the uterine
weight of immature rats with a median effective
dose (ED50) in the range of 1000 to 1500 mg/kg/day
(dietary administration). A continuous breeding study
revealed that the exposure of mice to high doses of
BP3 reduces the number and the weight of offspring
and increases the mortality of the lactating dams.
The no observed adverse effect level (NOAEL) for
reproductive toxicity was 1.25% in feed.57 However,
a dermal application of high doses (up to 400 mg/kg/
day) to male mice does not affect reproductive organ
weight or production and quality of sperm.58
In humans, a reduction of birth weight in girls
and an increase in boys may also be associated with
maternal exposure to oxybenzone,59 which has also
been detected in breast milk.60
2.1.2. Benzophenone-1
Benzophenone-1 (2,4-dihydroxybenzophenone,
BP1) is a common metabolite of oxybenzone. BP1
binds to oestrogen receptors obtained from rats’ uteri.
Its oestrogenic and anti-androgenic activities have
been confirmed in vitro (hERα and hAR assays).
oestrogenic activity has also been confirmed in vivo
in fishes (significant vitellogenin induction at 4.919
Ex vivo assays with testes from mice and rats
revealed that BP1 inhibits testosterone synthesis.63
Moreover, BP1 affects the early life-stage develop-
ment of the marine copepod Acartia Tonsa. Environ-
mental conditions, such as salinity and temperature,
influence the toxic effect. For instance, at 20oC, the
median effective concentration (EC50) was 1.1 mg/l
and at 15oC, 0.49 mg/l.64
Finally, endometriosis in women, which is an
oestrogen-dependent disease, is associated with ex-
posure to benzophenone compounds and especially
with exposure to BP1.65
2.1.3 Other benzophenone compounds
Benzophenone-2 (2,2′,4,4′-tetrahydroxybenzo-
phenone, BP-2) is another sun lotion component of
the benzophenone group. In vitro assays revealed
its ability to display oestrogenic, androgenic and
anti-androgenic activity.9 In addition, in utero expo-
sure of male mice to BP-2 causes hypospadias.66 Its
oestrogenic activity has been confirmed in vivo in
fishes.62,67,68 Exposure of fishes to BP-2 affects the
gonads, the secondary sex characteristics, spawning
activity and fertility with a lowest observed effect
concentration (LOEC) of 1.2 mg/l.67,68
Experiments with zebrafish showed that suliso-
Sun lotion chemicals as endocrine disruptors 35
benzone (Benzophenone-4, BP4) disrupts the normal
endocrine function of the animals (oestrogenic activity)
and induces alterations in the genes related to thyroid
development. The lowest effect concentration (LEC)
was found to be 30 μg/l.69 Furthermore, BP4 shows
oestrogenic/anti-oestrogenic and anti-androgenic
properties in vitro.9
Dioxybenzone (Benzophenone-8, BP8), which
is also a sun lotion benzophenone ingredient, shows
oestrogenic activity in vitro.70 4-hydroxybenzophenone
(or p-hydroxybenzophenone) is another benzophenone
compound with endocrine disrupting properties in
vitro.71 What is more, 4-hydroxybenzophenone dis-
plays endocrine activity in juvenile female rats and
increases the weight of their uterus after subcutaneous
2.2. Octyl methoxycinnamate
Octyl methoxycinnamate (ethylhexyl methoxycin-
namate, octinoxate, OMC) is a commonly used UV
filter with known endocrine disrupting properties.9,36
In rats, OMC causes various impairments, in-
cluding the alteration of the normal release of the
luteinizing hormone-releasing hormone (LHRH)
and of the amino acid neurotransmitters from the
This sunscreen filter can decrease
the normal serum concentrations of the hormones:
thyrotropin (thyroid-stimulating hormone, TSH),
thyroxine (T4) and triiodothyronine (T3) in rats.
This reveals a possible impact on the function of the
hypothalamic-pituitary-thyroid axis.74
OMC exhibits anti-oestrogenic and androgenic/
anti-androgenic activity but no oestrogenic activity in
hERα and hAR assays.
Furthermore, a two-generation
study with rats concluded that OMC has no oestrogenic
effect in vivo either. A NOAEL of 450 mg/kg bw/day
(dietary administration) for reproductive disorders
was established and a dose of 1000 mg/kg bw/day
was found to be able to delay the sexual maturation
of the offspring for a few days.75
Exposure to OMC by gavage leads to a decrease
of T4 concentration in female rats (dams) and affects
the reproductive and the neurological development
of their offspring. Exposure to 1000, 750 or 500 mg/
kg bw/day from gestation day 7 to postnatal day 17
negatively affected the sperm counts of the male
offspring.76 OMC also increases the uterine weight
of immature rats with an ED50 of 935 mg/kg/day
(dietary administration).
Moreover, the exposure
of the aquatic insect Chironomus riparius to OMC
affects its normal endocrine function.77
Skin absorption of OMC is possible, which ac-
counts for its presence in plasma, urine and human
Its presence in human milk leads to neo-natal
exposure, which is of particular concern.
2.3. 4-methylbenzylidene camphor
4-methylbenzylidene camphor (4-MBC, enzaca-
mene) disrupts normal endocrine function in rats,
fishes, aquatic molluscs and insects.37,77,79,80
In vitro assays (hERα and hAR) have revealed
its anti-oestrogenic and anti-androgenic properties.9
Exposure of rats to 4-MBC (dietary administration of
F0 generation and F1 until adulthood) increases the
uterine weight of the female offspring and the thyroid
weight of both sexes in the two generations.
delays male puberty and disrupts the normal female
sexual behaviour of the offspring (dietary administra-
tion of F0 generation and F1 until adulthood) with
a NOAEL of 0.7 mg/kg/day and a lowest observed
adverse effect level (LOAEL) of 7 mg/kg/day.10 An
ED50 of 309 mg/kg/day (dietary administration) was
determined in immature rats for increasing uterine
2.4. 3-benzylidene camphor
The UV filter 3-benzylidene camphor (3-BC)
exhibits endocrine disrupting activity (oestrogenic,
anti-oestrogenic and anti-androgenic) as demonstrated
using hERα and hAR assays.9 3-BC shows oestrogenic
activity not only in vitro but also in vivo in fish and
aquatic molluscs.62,80
3-BC delays male puberty and disrupts normal
female sexual behaviour and the oestrous cycle of
rat offspring (dietary administration as in the case
of 4-MBC, NOAEL: 0.07 mg/kg/day and LOAEL:
0.24 mg/kg/day).10 Additionally, less heavy rat uteri
are associated with exposure to 3-BC.37
Exposure to 3-BC is also associated with disorders
of the normal reproductive function of fish, produces
feminization of male secondary sex characteristics
and affects the gonads (male and female) and fertility
with a LOEC of 3 μg/l.68
More investigation is also needed to determine a
possible endocrine and reproductive disrupting role
of 2-Ethoxyethyl p-methoxycinnamate (cinoxate),
trolamine salicylate (or triethanolamine salicylate)
and Mexoryl SX (Ecamsule). Lack of evidence as
to endocrine disrupting properties and/or reproduc-
tive impairments characterizes the majority of the
remaining and less common ingredients as well. These
compounds include, among others, Amiloxate (Isoa-
myl p-Methoxycinnamate), Mexoryl SX (Ecamsule),
Uvinul A Plus (diethylamino hydroxybenzoyl hexyl
benzoate), octyl triazone (ethylhexyl triazone, Uvinul
T 150), polysilicone-15 (Parsol SLX) and Methyl
anthranilate (Meradimate).
Titanium dioxide (TiO
) and zinc oxide (ZnO)
are two metal oxides traditionally known for their
sunblocking properties.20 Sun lotion manufacturers
formerly used the bulk form of these materials, but
nanotechnology advances have made possible the use
of their nanoscale form. The new nanoscale ingredients
are more aesthetic, as they do not produce the charac-
teristic opaque film created by the largescale ones.84
Regarding their possible dermal penetration/ab-
sorption, there are studies that have shown that these
nanoparticles do not penetrate the skin deeper than
the stratum corneum in vitro or do not exhibit skin
penetration in vivo.85 However, Zn from ZnO nano-
particles can be absorbed by a healthy skin and can
be detected in human urine and/or blood samples.86
The parameter “healthy skin” is important because
if the skin has e.g. a disrupted stratum corneum, the
behaviour of these particles may be different.84
Nanoparticle forms of both metal oxides produce
reactive oxygen species (ROS) in the presence of UV
In general, ZnO nanoparticles are consid-
ered more toxic than TiO2 nanoparticles.87
3.1. Zinc oxide
Zinc is a necessary trace element for normal re-
productive function, such as normal spermatogenesis
and the oestrous cycle.88 However, a study revealed
that high doses of dietary zinc may cause apoptosis
of reproductive tissues in hens.89 Other experiments
have shown that zinc in high doses causes hormonal
problems in rats.90
PABA (para-aminobenzoic acid, p-aminobenzoic
acid, 4-aminobenzoic acid), OD-PABA (Padimate O,
Octyl-dimethyl PABA, Ethylhexyl dimethyl PABA)
and Et-PABA (Ethyl-4-aminobenzoate) are chemicals
known for their ability to absorb UV radiation.
Regarding likely effects of PABA on the endocrine
and/or the reproductive system, research until now is
limited. A study has demonstrated anti-oestrogenic
activity in a hERα assay,9 but other experiments have
not revealed a noteworthy connection or a negative
effect. For instance, the exposure of pregnant rats
to PABA at 50 mg/kg (intragastric administration)
slightly affects the normal development of the body
mass of rat foetuses, but this effect was characterized
as “insignificant”, as body mass development usually
becomes normal after birth.81
OD-PABA displays oestrogen antagonistic activity
in vitro
and shows an endocrine effect in the aquatic
insect Chironomus riparius.
Et-PABA is also an
endocrine disrupting agent. Oestrogenic activity in
vitro and in vivo in fishes has been shown.
chemicals display anti-androgenic activity in vitro.9
2.6. Other organic filters
The organic UV filters octocrylene (OC), ho-
mosalate (HMS, homomethyl salicylate) and octis-
alate (octyl salicylate, OS or ethylhexyl salicytate,
EHS) show anti-oestrogenic, androgenic and anti-
androgenic activity in hERα and hAR assays.9 The
available data, e.g. for octocylene,82 does not reveal
reproductive risks.
Tinosorb M (methylene bis-benzotriazolyl te-
tramethylbutylphenol, bisoctrizole) and Tinosorb S
(bis-ethylhexyloxyphenol methoxyphenyl triazine,
bemotrizinol) are organic compounds used in sun
lotions. None of these ingredients is expected to have
an endocrine disrupting activity (in vitro assays and
in vivo subcutaneous administration).83 In any case,
both chemicals are relatively new components and
more research is needed on their possible effects on
the endocrine and the reproductive systems.
Avobenzone (butyl-methoxydibenzoylmethane)
is additionally an active compound, regarding which
more investigation is indicated. Limited evidence
suggests that it does not display oestrogenic activity.
Sun lotion chemicals as endocrine disruptors 37
In mice, ZnO nanoparticles accumulate in liver
and cause oxidative stress, DNA damage and apo-
ptosis in its cells two weeks after oral exposure to
300 mg/kg.
Furthermore, in Cyprinus carpio fishes,
ZnO nanoparticles bioaccumulate more easily and
cause more oxidative damage compared to its bulk
ZnO nanoparticles are toxic for white sea urchin
embryos with an EC50 of 99.5 μg/l.
ZnO nanoparticle
aggregates affect zebrafish and cause delayed embryo
hatching (84 hours EC50 for this study: 23.06 mg/l)
and likely malformations in embryos and larvae.
aquatic toxicity of ZnO nanoparticles is attributed to
ions (mainly), or to the nanoparticles themselves,
or to a possible combination of both.94-96
Moreover, a study revealed that the nanoforms
of ZnO can impede normal cocoon production (a
reproductive parameter) of earthworms in artificial
soil conditions, exhibiting greater toxicity attributed
to the dissociation of Zn ions.97
3.2. Titanium dioxide
Nanoparticles of TiO2 present a risk factor for the
male mouse reproductive system, affecting the normal
density and motility of the sperm at high doses of
exposure (500 mg/kg, intraperitoneal injection every
other day).98 The intravenous injection of TiO2 nano-
particles with a diameter of 35 nm disrupts normal
pregnancy progression in already pregnant mice.
Chronic exposure (21 days) of the aquatic organism
Dapnia magna to nanoparticles of TiO2 (0.1, 0.5, 1,
5 mg/l) inhibits its reproduction.100
Chronic exposure (13 weeks) of zebrafish to 0.1
mg/l and 1 mg/l of TiO
nanoparticles negatively
affects their reproductive system and reduces egg
production.101 Chronic exposure (21 days) to na-
noparticles of TiO2 (length: 50 nm, width: 10nm)
coated with hydrated silica, dimethicone/methicone
copolymer and aluminum hydroxide (T-Lite SF-S)
affects the reproduction of Daphnia magna freshwater
invertebrates in a negative way. A LOEC of 10 mg/l
and a no observed effect concentration (NOEC) of
3 mg/l were defined. The concentration of 10 mg/l
caused a two-day delay in the production of the first
offspring. The EC50 for the reproductive outcomes
was 26.6 mg/l.102
Another known effect related to reproductive tox-
icity issues is the decrease of cocoon production by
earthworms in artificial soil due to exposure to nano
Furthermore, a possible endocrine role of TiO
nanoparticles can be deduced from the induction of
insulin resistance in liver-derived cells.103
The use of nanoparticles raises safety issues. One
of the most important is possible transport through
the placental barrier leading to potential disruption
of normal embryogenesis and to foetal exposure.104
nanoparticles are detected in the male offspring
after subcutaneous administration to pregnant mice
and cause reproductive impairments leading to prob-
lematic spermatogenesis.105
Sun lotions can act as penetration enhancers by
favouring the flux of hazardous chemicals through
the skin.106-108 A study had demonstrated that these
products can increase the penetration of benzene
through human skin in vitro, but it did not identify
the culpable components.106 However, a newer study
showed that the active ingredients octyl methoxycin-
namate, oxybenzone, sulisobenzone, OD-PABA,
octisalate, homosalate and the insect repellent DEET
can increase the penetration of 2,4-dichlorophenoxy-
acetic acid through hairless mouse skin in vitro. Only
Octocrylene did not promote the uptake.108
Many of the chemicals that penetrate the skin more
easily show endocrine disrupting activity and/or cause
reproductive impairments. For instance, as mentioned
above, some sun lotions can act as penetration en-
hancers for 2,4-dichlorophenoxyacetic acid.107,108 This
substance, known for its endocrine disrupting role,
is a widely used herbicide. 2,4-dichlorophenoxyacetic
acid can affect normal development of the central
nervous system of rats and their spermatogenesis.
It also disrupts normal rat maternal behaviour.112 Farm-
ers who are exposed to herbicides and daily spend
many hours outside and use sunscreens to protect
themselves from UV radiation face a higher risk for
this kind of penetration.107,108
Therefore, possible endocrine disrupting activity
and/or impairment of the reproductive system caused
by increase of exposure to other chemicals can be
an indirect effect of the use of UV filter chemicals.
Sun lotions are formulated using inactive ingre-
dients such as parabens (alkyl esters of p-hydroxy-
benzoic acid). Parabens are common preservatives
of pharmaceutical and cosmetic products. Not all
sun lotions contain parabens and many manufac-
tures have replaced them with other substances. For
instance, during this research, a brand was identified
whose previous formulations contained three parabens
(propylparaben, butylparaben and methylparaben),
but its new ones are paraben-free. Other ingredients
(both inactive and active) also changed, although it
was commercialized as the same product with the
same SPF. Other common inactive ingredients are
dimethicones, phthalates, disodium ethylenediami-
netetraacetate (EDTA), triethanolamine and water.
5.1. Parabens
Parabens show endocrine disrupting activity and
are known to negatively affect the male reproductive
Below is a selection of examples that arouse
concern among scientists about their use in cosmetics.
Male rats exposed to propylparaben at four con-
centrations (0.00% (control) and 0.01, 0.1 and 1.0%)
in their diet revealed a dose-dependent decrease of
the testosterone concentration in the serum.114 Bu-
tylparaben shows the same effect in male mice and
inhibits their spermatogenesis.115 Maternal rat expo-
sure to butylparaben affects the development of the
reproductive system of the F1 male offspring after
subcutaneous injections, leading to decreased sperm
count and motility.116
Propylparaben, butylparaben, methylparaben and
ethylparaben display oestrogenic activity in vitro.
However, oral exposure of rats did not result in oes-
trogen activity. On the other hand, subcutaneous
administration of butylparaben resulted in oestrogenic
effects in vivo in rats.117
Parabens have the ability to display 17β-oestradiol-
like effects and bind to the alpha and beta oestrogen
receptors.118 The beta oestrogen receptor (ERβ) may
be engaged in the development of melanoma.119 This
is the basis for major concern regarding the binding
of parabens with oestrogen receptors.117,118 Exposure
to parabens may also cause increased oestradiol con-
centrations in the skin as a result of their ability to
inhibit the oestrogen sulfation mechanism.120
Therefore, the use of endocrine disruptors, such
as parabens, in cosmetic products for cutaneous use
(e.g. sun lotions) poses significant health risks.
thermore, it should be mentioned that methylbaraben
enhances the negative effect of UV-B radiation on
skin keratinocytes.121
5.2. Dimethicones
Siloxanes are inactive ingredients that are used in
cosmetic products such as sun lotions and creams.
The most commonly used are octamethylcyclotet-
rasiloxane (D4), decamethylcyclopentasiloxane (D5)
and dodecamethylcyclohexasiloxane (D6). The mix-
tures containing mainly these siloxanes are known
as “cyclomethicones”. Sun lotion manufacturers use
polydimethylsiloxane silicone (PDMS) formulations
known as “dimethicones” in which D4 is present in
their final formulation. A dimethicone can be com-
bined with whatever/any form of silica to produce
“simethicone”, which is another inactive ingredient
in sun lotions.122-124
D4 shows endocrine disrupting activity and causes
reproductive disorders. More in particular, D4 exhib-
its weak oestrogenic and anti-oestrogenic activity in
What is more, the daily exposure of rats to
D4 vapour in a variety of concentrations provokes
a longer oestrous cycle and decreases fertility indi-
ces. A NOAEL of 300 ppm for female reproductive
toxicity has been determined, while the NOAEL for
males is 700 ppm.126
5.3. Phthalates
Even though phthalates are not mentioned in the list
of ingredients, they might be part of the formulation
of the ingredient known as “fragrance”, “perfume”
and “parfum” (or other related terms). For manufac-
turers it is not compulsory to reveal the components
of their fragrances because the composition of these
products can be kept secret.49,127 Exposure to phthalates
might also result from their migration from the plastic
packaging into the cosmetic product.128
Numerous papers have been published on the
health effects of phthalates such as diethyl phthalate
(DEP), di-n-butyl phthalate (DBP) and di(2-ethylhexyl
phthalate (DEHP) and of their metabolites such as
mono(2-ethylhexyl) phthalate (MEHP).129-133 This
overview is limited to a few characteristic aspects of
Sun lotion chemicals as endocrine disruptors 39
their effects on the endocrine and the reproductive
Exposure of female rats to DEHP reduces oestra-
diol concentration in serum, prolongs the oestrous
cycle and inhibits ovulation.
Further, DEHP shows
anti-androgenic activity of DEHP in rats.136 In utero
and during lactation, DEHP causes abnormalities of
the male reproductive tract in rats and reduces daily
sperm production.
An in vitro experiment with
human spermatozoa revealed that the previously
mentioned phthalates and di-n-octyl phthalate (DOP)
affect sperm motility.138
5.4. Other inactive ingredients
Disodium EDTA is commonly used in sun lotions.
The disodium salt of EDTA disturbs the binding of the
Vasoactive Intestinal Peptide (VIP) to the membranes
of the macrophages with a Half-maximal Inhibitory
Concentration (IC50) of 5.4 mM.139
Furthermore, there are other inactive ingredients
which are not harmless. Triethanolamine irritates
the upper respiratory tract of rats with a 90-day no
observed adverse effect concentration (NOAEC) of
4.7 mg/m
and produces systemic toxicity at high
doses.140 Moreover, in aquatic organisms chronic ef-
fects cannot be excluded.141 Many other ingredients
induce health problems such as allergic reactions.
Therefore, there are hidden dangers related to the
inactive ingredients. Some of them show endocrine/
reproductive impairments, but more research is re-
quired to identify and quantify these hazards.
Vitamin D is necessary for the development and
the maintenance of a healthy skeleton.18 Ninety per-
cent of the vitamin D essential for good health is
produced cutaneously.145 More specifically, UV solar
radiation is necessary for the cutaneous synthesis of
previtamin D318 and the wavelengths of the UV-B
region are the most efficient for this synthesis.18,146
The active ingredients in sun lotions reduce exposure
to and absorption of UV-B radiation through the skin.
Consequently, active ingredients inhibit the produc-
tion of the vitamin.147
When the cutaneous synthesis is insufficient, ad-
ditional intake through food or through supplements
is recommended. Vitamin D deficiency has been
associated with skeletal problems, such as rickets in
children and osteomalacia in adults, as well as with
a variety of cancers.148
Vitamin D deficiency impedes the secretion of
insulin from isolated rat pancreas cells
and it causes
reproductive and fertility deficiencies in both female
and male rats.150,151
Vitamin D deficiency during human pregnancy is a
significant risk factor for preeclampsia.
In addition,
low vitamin D intake during pregnancy is associated
with decreased birth weight.153
Many active ingredients of sun lotions pose health
risks, while they also negatively affect environmental
quality, and in particular aquatic life.
Commercial sun lotions and creams usually con-
sist of more than one chemical filter to achieve the
desirable level of protection.
Consequently, users are
exposed to a cocktail of chemicals. Harmful cocktail
effects might emerge even if the endocrine disrupting
chemicals are present in concentrations lower than
their individual NOEC.
Sun lotions are a typical
cocktail example because they contain a variety of
substances with documented endocrine disrupting
activity (UV filter mixtures).156
An individual consumer applies a relatively small
amount of a sun protection lotion, which is in the order
of micrograms per cm2,157 but the total quantity used
by all consumers together is thousands of tons. It has
been estimated that annually 4000-6000 tons enter the
aquatic environment in reef areas by washing off.158
Concentrations of organic filters found in natural
waters are of the order of ng/l, while in contaminated
waters they reach the order of μg/l.68,159 Although the
concentrations are still low, it should be noted that
sun lotions and creams persist in the environment for
up to a century and the currently widespread use of
these commercial products may drastically increase
their environmental levels. Nanoparticles such as TiO
(which are relatively new ingredients) are measured
in waters in concentrations of μg/l.162
The fate and the properties of these chemicals and
of their degradation products and their possible ability
to produce combination effects determine their final
impact. The current low concentrations in natural
waters are no guarantee for the absence of negative
effects. Furthermore, the properties of the by-products
in swimming pool waters, where the concentration of
UV filters can be of the order of μg/l,163 may conceal
significant threats. For instance, it has been shown that
the chlorination process (chlorine is used to disinfect
swimming pool waters) is able to produce mutagenic
substances if octyl methoxycinnamate is present.164
Consumers use sun lotions to protect themselves
from the harmful effects of solar UV radiation. How-
ever, a possible inadequate application combined
with the ignorance of the real effects of UV radiation
promotes a false sense of safety. What is more, many
sun lotion ingredients are associated with health risks,
including endocrine and reproductive impairments.
Apart from personal use and subsequent exposure
to these agents through skin contact, exposure also
occurs through inhalation and ingestion, especially
during swimming.
In crowded swimming areas,
large amounts of sun lotion chemicals end up in the
water and exposure becomes more complex.
The proper use of cosmetics, including sun lotions,
is advantageous for health, but special emphasis should
also be given to complementary protection measures,
such as appropriate clothing and avoiding of exposure
during the hours of highest sunlight intensity.5,166
Endocrine and reproductive impairments are known
to be caused in aquatic organisms, such as zebrafish
and Dapnia magna, by some sun lotion agents.69,100
Amongst other effects, sun lotion chemicals also
contribute to the bleaching of coral reefs.
the “ubiquity” of these emerging pollutants in aquatic
environments raises bioaccumulation and biomag-
nification issues.167,168 Consequently, the danger for
aquatic life cannot be ignored.
The increasing use of sun lotions, their continuous
washing off from the surface of the human body in
the water and indirect environmental contamination
through waste water treatment plants necessitates
an immediate and appropriate response to this new
emerging hazard.169
There are knowledge gaps concerning the properties
of sun lotion chemicals that should be addressed by
future research. The issues that need special considera-
tion include possible bioaccumulation, the effects that
result from the combination of these chemicals and the
effects of their metabolites and of their degradation
compounds. Furthermore, the likely involvement of
the ERβ in the development of melanoma and topical
treatment with cosmetics containing substances with
oestrogenic activity (e.g. UV filters, parabens) are two
issues that require special attention.113,119
Are sun lotion chemicals endocrine disruptors?
These ingredients do have endocrine disrupting
properties and affect the reproductive system of ex-
perimental animals, revealing a potential danger for
wildlife. The precise in vivo effects on humans are
difficult to measure and the human data are limited.
However, adverse health effects in humans cannot be
excluded and the increasing use of sun lotions may
be an unidentified threat for normal human endocrine
and/or reproductive function.
Formulations of commercial sun lotions are mix-
tures of active and inactive ingredients both of which
are related to health hazards. Different active (and
inactive) ingredients are combined to offer a better
level of UV protection. This makes their composition
more complex, but also increases the possibility of
combination effects. Due to the current widespread
use of sun lotions and to the existing scientifically
documented knowledge, the raising of awareness
of the subject is more important than ever before.
Aquatic toxicity issues require more investigation,
and this new emerging environmental hazard should
not be underestimated.
The authors declare no conflict of interest.
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... Reports to date, emphasize how chemical and mineral filters reach coastal waters and through bioaccumulation and biomagnification issues affect marine organisms (Fent et al., 2010;Wood, 2018). Another concern that has been object of a fierce debate is the health safety of the chemical filters, since there are studies where ingredients of this group are described as penetration enhancers and others present endocrine disruption characteristics (Coronado et al., 2008;Maipas and Nicolopoulou-Stamati, 2015). These sustainability aspects of UV filters increased interest in natural compounds derived from renewable sources that may exhibit a filtering activity, as the so-called UV absorbing phytochemicals (i.e., polyphenols, carotenoids, vitamins and anthocyanidins) (Beerling, 2014;Tampucci et al., 2017). ...
In recent years, sustainability on the cosmetics industry has received growing interest from consumers, cosmetics industries and organizations, as well as academics from various disciplinary fields. Increasing concerns about cosmetics safety, environmental impacts as deforestation and social impacts as those resulting from unfair trade have intensified attention given to such topic. While sustainability impacts occur through all phases of the cosmetic product life cycle, selection of raw materials is deserving of greater attention as information on this topic remains scattered and diffuse. Formulating with alternative ingredients considered more sustainable can be quite challenging due to possible lack of performance, instability and aesthetic limitations normally associated with their use. This paper discusses the relation between sustainability and the cosmetics industry, the factors stimulating the developments on this field, the need to assess those and the available tools, alongside with the sustainability impacts produced during all the product life cycle. The analysis reveals cosmetics sustainability as a complex and multifaceted issue that cannot be evaluated considering single aspects, but using an integrated assessment about the environmental, social and economical dimensions and about the final product quality and performance.
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Sunscreen and sunblock are crucial skincare products to prevent photoaging and photo-carcinogenesis through the addition of chemical filters to absorb or block ultraviolet (UV) radiation. However, several sunscreen and sunblock ingredients, mostly UV filters, have been associated with human and environmental safety concerns. Therefore, the exploration and discovery of promising novel sources of efficient and safer compounds with photoprotection-related activities are currently required. Marine invertebrates, particularly their associated microbiota, are promising providers of specialized metabolites with valuable biotechnological applications. Nevertheless, despite Actinobacteria members being a well-known source of bioactive metabolites, their photoprotective potential has been poorly explored so far. Hence, a set of methanolic extracts obtained from Cliona varians-derived actinomycetes was screened regarding their antioxidant and UV-absorbing capacities (i.e., photoprotection-related activities). The active extract-producing strains were identified and classified within genera Streptomyces, Micrococcus, Gordonia, and Promicromonospora. This is the first report of the isolation of these microorganisms from C. varians (an ecologically important Caribbean coral reef-boring sponge). The in vitro cytotoxicity on dermal fibroblasts of oxybenzone and the selected active extracts revealed that oxybenzone exerted a cytotoxic effect, whereas no cytotoxic effect of test extracts was observed. Accordingly, the most active (SPFi > 5, radical scavenging > 50%) and nontoxic (cell viability > 75%) extracts were obtained from Streptomyces strains. Finally, LC-MS-based characterization suggested a broad chemical space within the test strains and agreed with the reported streptomycetes' chemodiversity. The respective metabolite profiling exposed a strain-specific metabolite occurrence, leading to the recognition of potential hits. These findings suggest that marine Streptomyces produce photoprotectants ought to be further explored in skincare applications.
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Marine-derived fungi proved to be a rich source of biologically active compounds. The genus Penicillium has been extensively studied regarding their secondary metabolites and biological applications. However, the photoprotective effects of these metabolites remain underexplored. Herein, the photoprotective potential of Penicillium echinulatum, an Antarctic alga-associated fungus, was assessed by UV absorption, photostability study, and protection from UVA-induced ROS generation assay on human immortalized keratinocytes (HaCaT) and reconstructed human skin (RHS). The photosafety was evaluated by the photoreactivity (OECD TG 495) and phototoxicity assays, performed by 3T3 neutral red uptake (3T3 NRU PT, OECD TG 432) and by the RHS model. Through a bio-guided purification approach, four known alkaloids, (-)-cyclopenin (1), dehydrocyclopeptine (2), viridicatin (3), and viridicatol (4), were isolated. Compounds 3 and 4 presented absorption in UVB and UVA-II regions and were considered photostable after UVA irradiation. Despite compounds 3 and 4 showed phototoxic potential in 3T3 NRU PT, no phototoxicity was observed in the RHS model (reduction of cell viability < 30%), which indicates their very low acute photoirritation and high photosafety potential in humans. Viridicatin was considered weakly photoreactive, while viridicatol showed no photoreactivity; both compounds inhibited UVA-induced ROS generation in HaCaT cells, although viridicatol was not able to protect the RHS model against UVA-induced ROS production. Thus, the results highlighted the photoprotective and antioxidant potential of metabolites produced by P. echinulatum which can be considered a new class of molecules for photoprotection, since their photosafety and non-cytotoxicity were predicted using recommended in vitro methods for topical use.
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Faced with the ban of some organic UV filters such as octinoxate or avobenzone, especially in Hawaii, it became essential to offer new alternatives that are both renewable and safe for humans and the environment. In this context, a class of bio-based molecules displaying interesting UV filter properties and great (photo)stability has been developed from Meldrum's acid and bio-based and synthetic p-hydroxycinnamic acids, furans and pyrroles. Moreover, p-hydroxycinnamic acid-based Meldrum's derivatives possess valuable secondary activities sought by the cosmetic industry such as antioxidant and anti-tyrosinase properties. The evaluation of the properties of mixture of judiciously chosen Meldrum's acid derivatives highlighted the possibility to modulate secondary activity while maintaining excellent UV protection. Meldrum's acid derivatives are not only competitive when benchmarked against organic filters currently on the market (i.e., avobenzone), but they also do not exhibit any endocrine disruption activity.
Sunscreens are widely prescribed and used to prevent skin cancer; however, they have been reported to contain various chemicals which mimic hormones and disrupt hormonal functioning in humans. The aim of this study was to develop topical nanogel for skin cancer prevention using an antioxidant compound quercetin (Qu) and inorganic titanium dioxide (TiO2). Two formulations of Qu nanocrystals were optimized with low and high concentration of drug using the Box-Behnken design with the quadratic response surface model and further homogenized with TiO2. Qu nanocrystal (0.08% and 0.12%) formulations showed a particle size of 249.65 ± 2.84 nm and 352.48 ± 3.56 nm with zeta potential of − 14.7 ± 0.41 mV and − 19.6 ± 0.37 mV and drug content of 89.27 ± 1.39% and 90.38 ± 1.81% respectively. Scanning electron microscopy (SEM) images showed rod-shaped nanocrystals with a particle size below 400 nm. Qu (0.08%), Qu (0.12%), Qu (0.12%) + TiO2 (5%), and Qu (0.12%) + TiO2 (15%) nanogels showed over 70% drug release with significantly (p < 0.001) enhanced skin deposition of Qu as compare with Qu suspension within 24 h. The average numbers of tumor, tumor volume, and percentage of animals with tumors at onset in the Qu (0.12%) + TiO2 (15%) nanogel-pretreated group was found to be significantly (p < 0.05) less as compared with the UV only exposed group. Further, Qu (0.12%) + TiO2 (15%) nanogel significantly (p < 0.001) downregulated COX-2, EP3, EP4, PCNA, and cyclin D1 expressions in contrast to Qu and TiO2 only pretreated groups. Therefore, novel combination of Qu (0.12%) + TiO2 (15%) with enhanced skin deposition can be used as a chemopreventive strategy in UVB-induced skin photocarcinogenesis.
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Background Premature skin aging results from exposure to a range of environmental factors, primarily ultraviolet radiation, but also high‐energy visible light in the blue spectrum, infrared radiation, and environmental pollution. These extrinsic factors result in the generation of reactive oxygen species which promote photoaging and DNA damage resulting in skin cancers. Aims To formulate skincare products utilizing a new coating applied to zinc oxide and titanium dioxide particles and complimentary skincare ingredients to provide broad protection against a range of environmental insults. Methods A cross‐polymer, multifunctional coating of silicate, polyalkylsilsesquioxane, and polydimethylsiloxane moieties increases the photostability and decreases the reactivity of mineral sunscreen agents when interacting with energy sources. These products are also formulated with antioxidants to minimize free radical propagation. Additionally, this coating improves the esthetic feel of mineral sunscreens, while the appearance is enhanced by formulating products with a blend of iron oxides. Results A series of in vitro and ex vivo studies demonstrated the ability of mineral‐based products formulated with the new multifunctional coating to provide protection against ultraviolet radiation, high‐energy visible light, infrared radiation, and environmental pollution. Conclusion Newly formulated mineral‐based skincare products provide environmental protection, are ecologically safe, and can replace chemical‐based sunscreen ingredients.
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Ultraviolet (UV) filters are chemicals widely used in personal care products (PCPs). Due to their effect as endocrine disruptor compounds (EDCs), the toxicity of UV filters is a current concern for human health. EDC exposure may be correlated to cardiovascular diseases (CVD), but to our knowledge, no studies assessed the UV filters effects as human EDCs at the vascular level. Octylmethoxycinnamate (OMC) is the world’s most widely used UV-B filter, present in more than 90% of PCPs. Due to its demonstrated multiple hormonal activities in animal models, this substance is also suspected to be a human EDC. The purpose of this study was to assess the rapid/short-term effects of OMC on arterial tonus and analyse its mode of action (MOA). Using human umbilical arteries, the endocrine effects of OMC were evaluated in in vitro (cellular and organ) experiments by planar cell surface area (PCSA) and organ bath, respectively. Our data show that OMC induces a rapid/short-term smooth muscle relaxation acting through an endothelium-independent MOA, which seems to be shared with oestrogens, involving an activation of soluble guanylyl cyclase (sGC) that increases the cyclic guanosine monophosphate (cGMP) intracellular levels and an inhibition of L-type voltage-operated Ca2+ channels (L-Type VOCC).
Sunscreens are the most popular way of protection against sunburn. Other possible indications are reduction of the risks of extrinsic aging and skin cancer. Inorganic and organic filters are used. Organic filters, such as PABA derivatives, cinnamates, benzophenones, and octocrylene may possess the risk of unwanted adverse events such as photo-allergy or negative environmental impact. All sunscreens that are used according to the manufacturers advice will reduce vitamin-D synthesis.
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Marine ecosystems are increasingly threatened by the release of personal care products. Among them, sunscreens are causing concern either for the effects on skin protection from UV radiation and for the potential impacts on marine life. Here, we assessed the UVA protective efficacy of three sunscreens on human dermal fibroblasts, including two common products in Europe and USA, and an eco-friendly product. The sunscreens’ effects were also tested on Paracentrotus lividus, a marine species possibly threatened by these contaminants. We found that all tested sunscreens had similar efficacy in protecting human fibroblasts from UVA radiation. Conversely, the sunscreens’ effects on embryo-larval development of P. lividus were dependent on the product tested. In particular, the USA sunscreen, containing benzophenone-3, homosalate and preservatives, caused the strongest impact on the sea urchin development, whereas the eco-friendly sunscreen determined the weakest effects. These results suggest that although the tested products protected human skin cells from UVA-induced damage, they might severely affect the success of recruitment and survival of the sea urchin. Our findings underline the importance of developing eco-friendly sunscreens for minimising or avoiding the impact on marine life while protecting human skin from UV damage.
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Background: To investigate the associations of genetic polymorphism with high-density lipoprotein-cholesterol (HDL-C) levels in Iranian adolescents. Methods: This multicentre study was conducted on 10 - 18 year-old students from 27 provinces in Iran. Logic regression approach was used to determine the main effects and interactions of polymorphisms related to HDL-C levels. Results: The rs708272 polymorphism was significantly related to HDL-C levels. Moreover, rs708272 increased HDL-C levels and had a protective effect on HDL-C. The interaction of rs2230808 and rs5880 polymorphisms as well as the interaction of rs320 and rs708272 polymorphisms were associated with lower HDL-C levels. Furthermore, the interaction of rs320 and rs1801177 polymorphisms was associated with lower HDL-C levels. Conclusions: We found that not only single SNPs, but also interactions of several SNPs affect HDL-C levels. Given the high prevalence of low HDL-C in Middle Eastern populations, further genetic studies are required for detailed analysis.
Vitamin D deficiency is now recognized as a pandemic. The major cause of vitamin D deficiency is the lack of appreciation that sun exposure in moderation is the major source of vitamin D for most humans. Very few foods naturally contain vitamin D, and foods that are fortified with vitamin D are often inadequate to satisfy either a child's or an adult's vitamin D requirement. Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia, osteoporosis, and fractures in adults. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious diseases. A circulating level of 25-hydroxyvitamin D of >75 nmol/L, or 30 ng/mL, is required to maximize vitamin D's beneficial effects for health. In the absence of adequate sun exposure, at least 800–1000 IU vitamin D3/d may be needed to achieve this in children and adults. Vitamin D2 may be equally effective for maintaining circulating concentrations of 25-hydroxyvitamin D when given in physiologic concentrations.
We report the epidemiology of sunscreen allergy over a period of 5 years at the National Skin Centre. A total of 61 patients with suspected allergy to sunscreen underwent patch or photopatch testing to our sunscreen series from 1992 to 1996. The results were retrospectively analysed and evaluated. Out of these 61 patients, 5 were found to have positive patch test reactions to sunscreens. 2 were photoallergic, and 3 were allergic to active ingredients in sunscreens. The main causative allergens were 2-ethylhexyl-4-methoxycinnamate (Parsol MCX) and 2-hydroxy-4-methoxybenzophenone (oxybenzone). We conclude that sunscreen contact allergy is uncommon in our practice. (C) 1998 Decker Publishing Inc.
The biological efficacy (erythema action) of the radiation is dependent on wavelength. The unit SED (standard erythema dose) is a direct measure of the erythema action of radiation. The skin by itself absorbs UV radiation depending on the thickness of stratum corneum and the degree of pigmentation. When testing SPF of a sunscreen in humans 2 mg/cm2 is applied, in real life much less sunscreen is used 0.5 mg/cm2. It has been suggested that the protection is reduced exponentially when a thinner layer is used. The number of sunburn cells, cutaneous DNA damage, conversion of urocanic acid, and immu-nosuppression are diminished by sunscreen use. Human studies have indicated that the number of actinic keratoses as well as squamous cell carcinomas can be reduced if sunscreens are used regularly.
Components of normal human skinEmbryologyEpidermisThe dermal-epidermal junctionDermisLangerhans' cellsMast cellsBasophilsNerves and sense organsMerkel cellsBlood vesselsLymphatic systemRegional variation
Evaluation of Subchronic (13 Week), Reproductive, and in Vitro Genetic Toxicity Potential of 2-Ethylhexyl-2-cyano-3,3-diphenyl Acrylate (Octocrylene). Odio, M. R., Azri-Meehan, S., Robison, S. H., and Kraus, A. L. (1994). Fundam. Appl. Toxicol. 22, 355-368. Use of 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate (Octocrylene) in commercial sunscreen products has increased considerably in recent years. To support larger scale human exposure to this compound, additional toxicological information was needed in several key areas. The present studies evaluated subchronic toxicity, developmental toxicity, and in vitro genotoxic potential of Octocrylene. In the subchronic study, male and female New Zealand white (NZW) rabbits treated topically with concentrations of octocrylene up to 534 mg/kg/day for 13 weeks showed slight to moderate dose-dependent skin irritation that correlated positively with a mild depression in body weight gain. Lack of associated histopathologic or clinical hematology abnormalities suggested that the body weight effect probably reflected a nonspecific response to topical irritation. In percutaneous developmental toxicity studies, NZW does were treated topically with Octocrylene at levels up to 267 mg/kg/day on Days 6 through 18 of gestation. Body weight gain, food consumption, and all maternal, reproductive, and offspring parameters evaluated were comparable between Octocrylene-treated and control animals. In the oral developmental toxicity assay, female CD-1 mice received oral doses of Octocrylene up to 1000 mg/kg/day on Days 8-12 of gestation. No evidence of maternal or developmental toxicity was seen at any dose tested. Genotoxicity was evaluated in vitro using the Chinese hamster ovary cell assay to assess clastogenicity and the mouse lymphoma cell assay to assess forward gene mutations. Octocrylene did not induce any significant increase in genotoxicity. This evaluation of toxicological potential supports the use of Octocrylene as a human photoprotectant.
Assessment of the Reproductive Toxic Potential of Dermally Applied 2-Hydroxy-4-methoxybenzophenone to Male B6C3FI Mice. Daston, G. P., Gettings, S. D., Carlton, B. D., Chudkowski, M., Davis, R. A., Kraus, A. L., Luke, C. F., Ouellette, R. E., Re, T. A., Hoberman, A. M., and Sambuco, C. P. (1993). Fundam. Appl. Toxicol. 20, 120-124. The potential of 2-hydroxy-4-methoxybenzophenone (HMB) to cause male reproductive toxicity was assessed in B6C3FI mice. HMB was administered topically for 13 weeks (5 days/week) to groups of 10 mice each at dosages of 0, 10, 20, 100, or 400 mg/kg/day. Additional high dosage and control mice were also included and euthanized at interim time points to characterize the time course of any effects. After 91 days (or at interim periods) mice were euthanized and reproductive organ weights, cauda epididymal sperm concentration and proportion of motile and abnormal sperm, and testicular spermatid concentration were determined. Testicular histology was evaluated in fixed tissue. HMB treatment had no effect on body weight gain or any of the male reproductive parameters assessed at any time point. These results indicate that topically applied HMB has no reproductive toxic potential in male B6C3FI mice at dosages as high as 400 mg/kg/day.