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REVIEW ARTICLE
Aluminium in cosmetics and personal care products
Sonia Sanajou
1,2
| Gönül S¸ahin
1
| Terken Baydar
2
1
Faculty of Pharmacy, Eastern Mediterranean
University, Famagusta, Turkey
2
Department of Toxicology, Faculty of
Pharmacy, Hacettepe University, Ankara,
Turkey
Correspondence
Sonia Sanajou, Faculty of Pharmacy, Eastern
Mediterranean University, 99628 Famagusta,
North Cyprus, Via Mersin 10, Turkey and
Department of Toxicology, Faculty of
Pharmacy, Hacettepe University, Ankara,
06100, Turkey.
Email: sonia.sanajou@emu.edu.tr;
soniasanajou@hacettepe.edu.tr;
sanajou19@hotmail.com
Abstract
Usage of inorganic ingredients like aluminium salts in cosmetics and personal care
products has been a concern for producers and consumers. Although aluminium is
used to treat hyperhidrosis, some worries have been raised about aluminium's role in
breast cancer, breast cyst and Alzheimer's disease. The human population is exposed
to aluminium from vaccines, diet, and drinking water, but the frequent use of
aluminium-based cosmetics might add additional local exposure. This paper reviews
literature to determine if aluminium-based products may pose potential harm to the
body. The dermal absorption of aluminium is not widely understood. It is not yet
known whether aluminium can travel from the skin to brain to cause Alzheimer's dis-
ease. Aluminium may cause gene instability, alter gene expression or enhance oxida-
tive stress, but the carcinogenicity of aluminium has not been proved yet. Until now,
epidemiological researches were based on oral information, which lacks consistency,
and the results are conflicting. Future studies should target real-life-based long-time
exposure to antiperspirants and other aluminium-containing cosmetics and personal
care products.
KEYWORDS
aluminium, Alzheimer's disease, antiperspirant, cancer, personal care products
1|INTRODUCTION
There is a high and still growing demand for cosmetics and personal
care products, including but not limited to fragrances, toothpaste,
shampoos, deodorants, lipsticks and antiperspirants. These products
have been given a notable place in our routine. They are mostly
applied to clean, beautify and enhance the skin texture, increasing
self-esteem and confidence (Cosmetics Europe, 2020; Fior
Markets, 2020; Zion Market Research, 2019). The market penetration
of personal care products and cosmetics in European countries is near
100%. For example, 94% of British women use deodorants, and 98%
of French women use liquid shampoo. In the United States, women
use at least 12 cosmetics products daily, and man uses six (Dell
et al., 2016). Although these products are accepted as safe, they con-
tain more than 12,000 different chemicals (Dell et al., 2016) such as
preservatives, plasticizers, fragrances, salts of metals (such as alumin-
ium), ultraviolet (UV) protectors and colourants (Sheikh, 2017), in
which less than 20% of them have been proven to be safe. However,
manufacturers and legislators mainly neglect toxic materials in these
products (Pineau et al., 2014). Some of the ingredients of shampoos,
antiperspirants, deodorants, vaginal douches and sprays have been
linked to breast cancer, early onset of puberty, ovarian cancer, endo-
metriosis, neurotoxicity (Dell et al., 2016) and obesity (NWHN, 2020).
The determination of a cosmetic ingredient's toxic potential is based
on a series of toxicity studies (Pineau et al., 2014; SCCS, 2010) regu-
lated by legislatures like the US Food and Drug Administration (FDA)
and the European Scientific Committee on Consumer Safety (SCCS).
As these products contact the skin for long periods, their toxic effects
should not be neglected. According to warning statements published
by FDA and SCCS (CFR, 2019; SCCS, 2011), cosmetics and personal
care products should not be applied to damaged, irritated or bleeding
skin. Shaving the underarm area increases the rate of skin damage and
irritation. Nevertheless, people mostly ignore the FDA and SCCS
warning and apply products like antiperspirants on the shaved skin or
often apply cosmetics over sensitive and thin skin (Zakaria &
Ho, 2015). This behaviour increases the rate of contact and
Received: 16 October 2020 Revised: 27 July 2021 Accepted: 29 July 2021
DOI: 10.1002/jat.4228
J Appl Toxicol. 2021;1–15. wileyonlinelibrary.com/journal/jat © 2021 John Wiley & Sons, Ltd. 1
absorption of the chemicals from the injured skin (Pineau et al., 2012).
Especially in heavy metals, chronic exposure leads to increased
absorption and bioaccumulation and increased toxic effects (Zakaria &
Ho, 2015). The usage of heavy metals such as lead, mercury, cadmium,
chromium and metals such as aluminium is a big concern in the cos-
metic and personal care industry (Health Canada, 2012). For example,
exposure to cadmium increases the risk of kidney damage or causes
bone degradation (Ayenimo et al., 2010). Chronic exposure to lead
causes harm to the nervous system, embryo and hematologic system
(Zakaria & Ho, 2015). Aluminium is one of the ingredients in antiper-
spirants (Darbre, 2009; Exley, 2004; Exley et al., 2007; Linhart
et al., 2017; Mandriota et al., 2016), sunscreens (Nicholson &
Exley, 2007), lipsticks (SCCS, 2020) and toothpaste (SCCS, 2020).
The human body is exposed to cosmetics and personal care prod-
ucts that contain aluminium salts daily. It has been hypothesized that
aluminium in these products may harm human health; therefore, it
should be removed from cosmetics and personal care products
(Darbre, 2016; Fakri et al., 2006; Flarend et al., 2001; Rodrigues-Peres
et al., 2013a, 2013b). However, antiperspirants are still prescribed in
hyperhidrosis (HH) treatment (Brown et al., 2014; Hosp &
Hamm, 2017). This review paper aimed to bring all different views
regarding the usage of aluminium in cosmetics and personal care
products and their possible link with breast cancer, breast cysts and
Alzheimer's disease (AD).
2|ALUMINIUM
Aluminium is the third most abundant metal on Earth (Klotz
et al., 2017). It is found in air, soil and food (Aguilar et al., 2008), as
flocculating agents in the treatment of water, in dialysis solutions, in
vaccines as adjuvants (Baydar et al., 1998, 1999) and in cooking uten-
sils (Aguilar et al., 2008). Antiperspirants containing aluminium are
used to treat HH, and some antacids contain aluminium (European
Commission, 2014; Klotz et al., 2017). According to the World Health
Organization (WHO), the provisional tolerable weekly intake (PTWI)
concentration of aluminium is 2 mg/kg body weight in food additives
(Bend et al., 2011). Several chemical compounds with aluminium are
in extensive use in various products and processes associated with
human activities. These compounds are aluminium chloride, alumin-
ium hydroxide (alumina trihydrate), aluminium nitrate, aluminium
phosphate, aluminium sulfate (alum), aluminium potassium (potash
alum), aluminium ammonium sulfate (ammonium alum) and aluminium
silicate (Igbokwe et al., 2019). Human is exposed to aluminium orally,
by inhalation or through the skin (Aguilar et al., 2008; Exley, 2013).
The absorption rate from the gastrointestinal tract is low. However, if
aluminium enters the circulatory system, transferrin is responsible for
its transportation, especially to the brain. Average serum aluminium
concentrations are about 1–3μg/L (Nie, 2018). Aluminium is distrib-
uted in different tissues, but it accumulates in the brain, bones and
kidney. Especially by ageing, the increase in the rate of accumulation
in the brain is noticed. New evidence showed that brain aluminium
concentration could reach 100 times over plasma concentration.
Moreover, aluminium passes from the placenta to the fetus and even
from milk to the baby. The excretion routes are mainly the kidney and
large intestine (Nie, 2018).
None of the body's biological functions depends on aluminium
(Inan-Eroglu & Ayaz, 2018). However, aluminium negatively affects
more than 200 critical biological reactions. The central nervous
system pathways affected by aluminium are axonal transport,
neurotransmitter synthesis, synaptic transmission, phosphorylation or
de-phosphorylation of proteins, protein degradation, gene expression,
peroxidation and inflammatory responses. Aluminium binds to
histone–DNA complex, induces conformational chromatin changes
and induces topological DNA changes (Banasik et al., 2005).
Aluminium might alter gene expression by inducing decreased
expression of neurofilament and tubulin. It also may alter the
expression of oxidative stress marker genes (superoxide dismutase 1,
glutathione reductase), the expression of amyloid precursor protein
(APP), β-APP secretase, neuron-specific enolase and RNA polymerase
I (Inan-Eroglu & Ayaz, 2018).
Aluminium has been suspected as a possible mutagen. It has been
shown that aluminium exposure causes negative results in most
in vitro mutagenic assays, such as DNA damage in a micronucleus
assay (Banasik et al., 2005). Moreover, it may cause chromosomal
aberrations in Comet assay (Lankoff et al., 2006; Lima et al., 2007).
Thus, aluminium may cause genomic instability in tissues like the
breast (Darbre et al., 2013). However, SCCS reported that aluminium
is not likely to pose a risk as systemic genotoxic when it comes in con-
tact with skin (SCCS, 2020).
Toxic effects of aluminium have been shown in neurological dis-
orders like AD (Inan-Eroglu & Ayaz, 2018; Mirza et al., 2017;
Nie, 2018), Parkinson's disease (Maya et al., 2016) and dialysis
encephalopathy (Krewski et al., 2007). Moreover, exposure to alumin-
ium has been shown to play a role in bone abnormalities, breast tissue
(Exley et al., 2007) and pulmonary granulomatosis (Taiwo, 2014). In
individuals genetically susceptible to Crohn's disease, aluminium is
linked to the induction and persistence of chronic relapsing intestinal
inflammation (Lerner, 2007).
3|ALUMINIUM-BASED COSMETICS AND
PERSONAL CARE PRODUCTS
The use of aluminium derivatives in antiperspirants, toothpaste and
lipstick in concentrations specified by the FDA and European regula-
tions (SCCS, 2020) is safe for human health. The aluminium com-
pounds that are used in cosmetics and personal care products are
alumina (aluminium oxide) (ASTM, 2012; CFR, 2019), aluminium
hydroxide (FDA, 2011), aluminium cholorhydrate (Darbre, 2005), alu-
minium citrate (Fiume et al., 2014), aluminium myristate (Becker
et al., 2010) and aluminium distearate (Cosmetic Ingredient Review
[CIR], 2005). FDA approved usage of these compounds in cosmetics
and personal care products. According to SCCS, current conventional
antiperspirants contain water-soluble salts of aluminium and/or alu-
minium zirconium. These compounds form insoluble gels. Lipstick and
2SANAJOU ET AL.
toothpaste generally contain aluminium colloidal colourant and water-
insoluble minerals (SCCS, 2020). According to the International Cos-
metic Ingredient Dictionary and Handbook, alumina is added in
cosmetics as an abrasive, absorbent, anticaking agent, bulking agent
or opacifying agent. Aluminium hydroxide is added as a buffering
agent, corrosion inhibitor and pH adjuster (Gottschalck &
Breslawec, 2012).
Alumina was reported in 523 leave-on products at concentra-
tions up to 60% (in nail products). It is reported to be used in
40 rinse-off products, 84 products applied around the eye at con-
centrations up to 30%, 87 lipsticks up to 6.7% and 104 skincare
preparations for up to 25%. Aluminium hydroxide was used in
572 leave-on products up to 10.1%, six rinse-off products up to
8.8%, 80 products used around the eye at up to 10.1%, 154 lipsticks
up to 7%, oral hygiene products up to 8.8% and six suntan prepara-
tions up to 0.9% (Becker et al., 2016). According to European Union
regulations about ingredients in cosmetics, the maximum allowed
concentration of aluminium zirconium chloride hydroxide is 20% as
anhydrous aluminium zirconium chloride hydroxide or 5.4% as
zirconium in antiperspirants, and aluminium fluoride allowed concen-
tration is 0.15% in oral products that have fluoride inside
(Regulation, 2009).
Aluminium chloride hexahydrate (ACH) is the most frequent
and effective topical medication to relieve moderate HH symptoms
(Gee & Yamauchi, 2008). HH is a chronic disorder of excess sweat
production that may significantly affect the quality of life
(Lee & Levell, 2014; Nawrocki & Cha, 2019). ACH preparations are
widely available, cost effective, and easy to use, rendering them a
first-line treatment (Walling & Swick, 2011). ACH concentrations
range from 6.25% to 40% in water, alcohol, ether or glycerol
(Sammons & Khachemoune, 2017). Over-the-counter (OTC)
antiperspirants contain a maximum concentration of 12.5% ACH.
Frequently used prescription formulations include 20% aluminium
chloride in ethyl alcohol, 6.25% aluminium tetrachloride and
12% aluminium chloride in sodium carbonate water (Gee &
Yamauchi, 2008).
The French agency in charge of cosmetic products
(AFSSAPS, 2011), the Norwegian Scientific Committee for Food
Safety (VKM, 2013) and the German institute in charge of cosmetic
products (Bfr Opinion, 2014) did the risk assessments regarding
aluminium in cosmetics and personal care products. In 2008, EFSA
reported the tolerable weekly intake of 1 mg Al/kg bw/week, and
in 2011, JECFA reported the PTWI of 2 mg Al/kg bw/week for
aluminium. The results from these two institutions were obtained
from studies of developmental neurotoxicity in laboratory animals.
The Norwegian Scientific Committee for Food Safety compared
their results from using aluminium-containing cosmetics and
personal care products with the tolerable levels reported by JECFA
and EFSA. They concluded that aluminium entering the body using
these products is higher than aluminium that enters the body
through diets (VKM, 2013). In 2014, SCCS, in answer to the
Norwegian report, published a document on the safety of aluminium
in cosmetics. According to SCCS, there are limited human data on
the dermal absorption of aluminium. The studies on dermal absorp-
tion of aluminium have poor quality or did not design according to
standard test protocols. Moreover, aluminium toxicity is based on
systemic exposure, and there is a lack of proper study to estimate
internal exposure to aluminium following cosmetic uses. Thus,
proper risk assessment cannot be applied. In this report, the NOAEL
value of 30 mg/kg bw/day (JECFA, 2012) was accepted in future
risk assessments (European Commission, 2014). Tietz et al. (2019)
did a risk assessment based on total consumer exposure to
aluminium and its derivatives from food, food additives, cosmetics
and food contact materials. They measured the weekly exposure to
aluminium in different age groups from different sources that
contain aluminium. Infants and toddlers are exposed to a high
amount of aluminium in the first 36 months of their life through
vaccines. The second source of aluminium for them is through food
and food contact materials. As infants are in the developmental
stage, considering the risk of neurotoxicity, the exposure rate should
be regulated and monitored carefully. In children (3–10 years old),
the exposure risk is low and does not exceed the EFSA and JECFA
(VKM, 2013) reported data. However, in children (11–14 years), as
they are exposed to cosmetics and personal care products like
antiperspirants and toothpaste, the exposure to aluminium can
exceed the allowed concentrations up to five times. It should be
considered that aluminium accumulates in the body and remains
there for a long time. Thus, exposure from earlier ages will increase
its burden. In adults, the exposure extends wider. Because adults
are more exposed to aluminium-containing products besides
food-containing aluminium, the exposure rate may exceed the
commonly accepted values by EFSA and JECFA (Tietz et al., 2019).
Overall, to reduce the risk of aluminium intake, the aluminium
sources that a person can contact, intentionally or unintentionally,
should be reduced or regulated.
In 2019, Cosmetics Europe submitted the results of a clinical
study on the absolute bioavailability of aluminium from dermal
exposure to antiperspirant to SCCS. This study that TNO did
calculated the dermal bioavailability of 0.00052% for aluminium. In
2020, SCCS accepted this percentage to be used in risk assessments
(SCCS, 2020).
The margins of safety (MoS) for each of the three cosmetic
product types, antiperspirants, lipstick and toothpaste, are presented
in Table 1. In Columns I and II of the table, the NOAEL amount as
30 mg aluminium citrate/kg bw/day was taken into consideration
obtained from the neurodevelopmental rat study. Then, it was
adjusted by considering the rat oral bioavailability (0.6%) of aluminium
citrate. Thus, the systemic exposure at the NOAEL is estimated to be
180 μg Al/kg bw/day. However, in Column II, the amount of
radiolabelled aluminium found in urine and faces for the estimations
of dermal absorption (0.00192%) has been taken into account.
However, the overall safety assessment did not change (SCCS, 2020).
Based on the MoS calculations and risk assessments, SCCS (2020)
reported new limitations on the usage of aluminium and its
compounds in cosmetics and personal care products: 6.25% in
non-spray deodorants or non-spray antiperspirants, 10.60% in spray
SANAJOU ET AL.3
deodorants or spray antiperspirants, 2.65% in toothpaste and 0.77%
in lipstick.
4|ALUMINIUM ABSORPTION THROUGH
THE SKIN
With a total area of 1.5 m
2
, the skin is the largest organ in the
human body. It has a complex structure with diverse functions
(Hu & He, 2021). The skin has three layers: The first outermost
layer, the epidermis, provides a waterproof barrier. The second
layer, the dermis, contains connective tissue, hair follicles and sweat
glands. The third layer, the hypodermis, is subcutaneous. The
stratum corneum, the outer part of the epidermis, consists of
keratin-rich cells located within the lipid intercellular matrix
(Figure 1) (Yousef et al., 2020).
Transport of topically applied products, such as antiperspirants or
sunscreens, would involve passive diffusion by trans- and paracellular
routes across the stratum corneum layer. Nevertheless, it is expected
to be minimal (Flarend et al., 2001). Topically applied substances
(Knorr et al., 2009) and nanoparticles (Rancan et al., 2012) use hair fol-
licles as penetration and absorption pathway. These substances can
reserve around hair follicles and release slowly to the surrounding
capillaries and systemic circulation (Rancan & Vogt, 2014).
Exposure to metals through the skin occurs by direct contact with
metals or objects containing metals. Metals that come in contact
with skin can be absorbed to the epidermis; even in some cases,
absorption to dermis and penetration to the systemic circulation were
reported. Allergic reaction is the primary local effect of contact with
metals such as chromium, nickel or cobalt. However, the rate of
metals' skin permeation has been underestimated (Filon, 2018). The
integrity of the skin barrier is an important factor in skin permeation.
TABLE 1 Margin of safety calculations for antiperspirant non-spray products, lipstick and toothpaste
III
Product
type
Antiperspirant
(roll-on/stick) Lipstick Toothpaste
Total systemic
body burden
Antiperspirant
(roll-on/stick) Lipstick Toothpaste
Total systemic
body burden
Systemic
exposure
(internal
dose) μg
Al/kg
bw/day
0.007 (dermal
exposure)
0.0015
(oral
exposure)
0.057 (oral
exposure)
0.0655 0.0265 (dermal
exposure)
0.0015
(oral
exposure)
0.057
(oral
exposure)
0.085
MoS (based
on an
internal
dose POD
of 180 μg
Al/kg
bw/day)
25,714 (dermal
exposure)
120,000
(oral
exposure)
3158 (oral
exposure)
2748 6792 (dermal
exposure)
120,000
(oral
exposure)
3158 (oral
exposure)
2117
Source: SCCS (2020).
FIGURE 1 The major layers of normal
skin. When antiperspirant comes in contact
with skin, aluminium in skin pH forms an
insoluble gel layer on the skin, which is
proposed to be the mechanism by which
antiperspirant prevents sweating. Aluminium
compounds in antiperspirants may use two
pathways shown in the figure to enter the
skin. (a) Through the hair follicle, aluminium
may enter the capillaries and from there to
the systemic circulation. (b) Aluminium
compounds may enter through the swear duct
4SANAJOU ET AL.
Any damage to the skin such as desquamation, fissures and cuts
would increase the rate of dermal absorption. Therefore, irritant con-
tact dermatitis is the first step towards allergic contact dermatitis
(Filon, 2018).
Hair follicles and sweat ducts are the possible vessels by which
aluminium access the epidermis, dermis and lymphatic system
(Figure 1). However, there is no considerable evidence that aluminium
applied on the skin enter the bloodstream and excrete from the kid-
ney. Nevertheless, it does not mean that aluminium cannot enter the
circulatory system from the skin. Considering the aluminium formula-
tion in cosmetics, the frequency of applying these products on the
skin and the regulations about these products' safety indicate alumin-
ium in cosmetic and personal care products as an important source of
local and systemic aluminium (Exley, 2013).
Aluminium formulations in the antiperspirant like aluminium
chlorohydrate at pH of the skin or sweat form an insoluble salt that
acts as a barrier to the skin and prevents sweating (Hostynek, 2003).
Moreover, aluminium makes complexes with the proteins on the skin's
surface and limits penetration through the stratum corneum
(Hostynek, 2003; SCCS, 2020). However, sweat is produced, but the
metallic salt prevents its secretion (Holzle & Braun-falco, 1984).
Bretagne et al. (2017) used a microfluidic T-junction device that
mimics the sweat duct's activity to measure the diffusion of alumin-
ium polycationic species in sweat counterflow. They reported that
aluminium polycations cause aggregation of sweat proteins. These
aggregated proteins alongside aluminium polycations bind to the wall
of the sweat duct and make a membrane. This membrane then cap-
tures species provided by the sweat flow and becomes a denser
obstacle. Therefore, aluminium salts show their antiperspirant activity
by precipitation on the sweat duct and remain outside of the body.
There is limited information on aluminium absorption and distri-
bution following dermal exposure. Anane et al. (1997) exposed Swiss
mice to 0.4 μg/day aluminium chloride for 20 days during gestation.
They reported that the aluminium level in the liver, brain, lung and kid-
ney of mice and their fetus increased significantly. They concluded
that transdermal absorption of aluminium should be considered.
Flarend et al. (2001) measured the amount of aluminium absorbed
from two volunteers' skin (one male and one female). They exposed
the skin to radiolabelled aluminium chloride on a bandage. The
absorption rate was measured by measuring the amount of aluminium
excreted by the urine. Only a small amount of aluminium was
absorbed (only 0.012% of the applied concentration), and this small
amount may not pose harm to antiperspirant users.
In another study in 2018, 12 women were subjected to dermal
contact with radioisotope-labelled aluminium for 4 weeks. In this
experiment, women used antiperspirant daily. The aluminium excre-
tion rate by urine and blood was measured. This study showed that
aluminium amount entered the body through the skin is small enough
not to pose toxic effects in the body (de Ligt et al., 2018).
Another study was conducted in 2012, according to the Organi-
zation for Economic Cooperation and Development (OECD). Pineau
et al. (2012) measured the amount of aluminium absorbed through
the skin utilizing Franz
TM
diffusion cell. Aerosol, roll-on and stick-type
antiperspirants were tested on five skin samples. They reposted that
the amount of aluminium absorbed through the skin was insignificant.
The sample (strip skin) exposed to the stick-type antiperspirant
showed higher absorption rates (Pineau et al., 2012).
Letzel et al. (2020) studies on dermal absorption of aluminium
from an antiperspirant under real-life conditions in 21 healthy volun-
teers with a history of low exposure to aluminium concluded that alu-
minium absorbed through the skin might not increase the total
systemic aluminium concentration significantly. They measured the
amount of aluminium before and after the application of aluminium-
containing antiperspirants in 14 days. There was no significant
increase in aluminium level in the blood or urine of the samples.
In 2003, a woman with bone pain and anaemia was diagnosed
with hyperaluminumnia. She used aluminium-containing antiperspi-
rant for the past 4 years without being exposed to any other alumin-
ium source. The analyses of her blood and urine samples showed
elevated aluminium levels higher than reference concentrations. The
symptoms of aluminium toxicity were relieved 3 months after termi-
nating the usage of antiperspirant, and the blood and urine levels of
aluminium decreased consequently (Guillard et al., 2004). A list of epi-
demiological studies on aluminium absorption through the skin has
been given in Table 2.
5|ALUMINIUM AND BREAST CYST
Breast's cystic disease is the most common benign breast disorder,
which has been reported in up to 7% of women living in America's
United States (Kowalski & Okoye, 2020). It is a result of blockage or
narrowing of the terminal lobular units of the breast duct. The meta-
bolic activity of lining epithelial cells of the ducts releases fluid to the
ducts. This fluid gathered and stocked in the blocked duct (Figure 2)
caused sacs full of liquid (Norwood, 1990). These cysts can be asymp-
tomatic or symptomatic with signs of pain and lumps on the breast
(Norwood, 1990). The exact molecular mechanism behind breast cyst
is not known (Kowalski & Okoye, 2020). However, it was proposed
that frequent usage of aluminium-containing antiperspirant may pose
a role in the breast cysts' incidence. It is reported that more than half
of the breast cyst happens at the upper outer quadrant of the breast.
Coincidentally, it is the closest location to the site where most women
apply aluminium-containing antiperspirants. The antiperspirants are
formulated to block the axilla's sweat glands close to breast ducts
blocked in the breast cyst (Darbre, 2019). Thus, it is hypothesized that
chronic application of antiperspirant in this region may cause absorp-
tion and accumulation of aluminium in the breast ducts and cause
obstruction (Montemarano et al., 1997; Skelton et al., 1993).
The amount of aluminium in the breast cyst has been investigated
to identify if it is a risk factor or not. The amount of aluminium in
breast fluid has been measured between 11 and 330 μg/L. In Type I
breast cyst (according to histology), the median concentration of alu-
minium was 150 μg/L (range 80–330 μg/L), and in Type II (based on
ion, protein and hormone levels), 32 μg/L (range 11–39 μg/L). The
amount of aluminium in serum 6 μg/L (range 3–9μg/L) is lower than
SANAJOU ET AL.5
in both cyst types. The difference between aluminium concentration
in two types of cysts is still under investigation. However, the concen-
tration of sodium and potassium ions might be involved. The
concentration of sodium ions is low, but potassium ion is higher in
Type I cyst. It is vice versa in Type II (Mannello et al., 2006, 2009).
Furthermore, chronic exposure to aluminium has been reported to
TABLE 2 List of studies on dermal absorption of aluminium
Experiment population Analysis method Results Reference
- Swiss pregnant female mice - The back of female mice was shaved;
20 μl of aluminium chloride solution
0.4 μg/day was applied to the skin for
20 days
- Aluminium quantified by graphite
furnace atomic absorption with Zeeman
correction
- Aluminium concentration was high in
different organs of mice
- Aluminium concentration was high in
fetus organs
Anane
et al., 1997
- A female and a male -Aluminium-26-labeled aluminium
chlorohydrate applied to the left axilla
surface shaved 1 day before
experiment and left for 6 days
- Samples indicate that in the male, at
least 48% (in 6 days) and in the female,
at least 31% (in 4 days) of the applied
aluminium was recovered from the skin
surface
- They reported aluminium presence in
the blood even 15 days after the
experiment
- Aluminium excretion started from the
first day of the experiment and
continued until 44 days (almost 80%–
90% of what was absorbed)
Flarend
et al., 2001
- Five skin biopsies were obtained from
the abdominal skin of a bank of
Caucasians humans ranging in age
from 29 to 52 years
- Cosmetic formulations:
aerosol (38.5% of aluminium chloride), a
roll-on emulsion (14.5% of aluminium
chloride) and a stick (21.2% of
aluminium chloride)
- The aluminium assays were performed
by Zeeman electrothermal atomic
absorption spectrophotometry (ZEAAS)
- The aluminium assays showed only little
transdermal absorption of aluminium
and particularly low cutaneous
quantities that varied according to the
formulations
Pineau
et al., 2012
- 12 healthy women - Roll-on formulation containing an
extremely rare isotope of aluminium
(
26
Al) as ACH
- A conservative estimated range for
dermal absorption of 0.002%–0.06%
was calculated from the urinary
excretion data, with a mean estimate of
0.0094%
- Total aluminium measurements showed
that antiperspirants make only a minor
contribution to systemic exposure
de Ligt
et al., 2018
- 6 female subjects -
26
Al/0.75 g antiperspirant formulation
was applied on each axilla
approximately 100 cm
2
- A complete urine collection, in 24-h
intervals for 10 days
- Analysis of aluminium levels on T-shirts,
wash (including the gauze), and tape
stripping and biopsies at the end of the
sampling period
- The mean dermal fraction absorbed
value of 0.00052% is regarded as an
appropriate value to use in risk
assessment.
- The overall recovery of the
26
Al applied
either topically or after IV injection was
found to be approximately 70%
SCCS, 2020
- 21 healthy subjects with low systemic
aluminium background
- They used a commercial aluminium-
containing antiperspirant for 14 days
- A questionnaire about shaving habits
and other sources of aluminium was
completed by subjects
- Aluminium levels were measured before
and after the exposure in 24-h urine
and plasma using atomic absorption
spectroscopy
- No increase in plasma or urine
concentration of aluminium before and
after sampling was reported
- Shaving habits did not affect the
systemic aluminium concentration
- No correlation between total systemic
aluminium concentration and the
amount of aluminium in antiperspirants
was reported
Letzel
et al., 2020
6SANAJOU ET AL.
change the sodium–potassium ATPase activity (Silva et al., 2007).
Therefore, exposure to aluminium might be behind the difference in
ion concentration in Type I and II breast cyst.
Studies also showed that aluminium concentration is significantly
higher in the defatted tissue of the breast's outer regions (Exley
et al., 2007). The high incidence of breast cysts in the breast's upper
outer regions (Darbre, 2016) can be related to regular aluminium
usage because of the high aluminium concentration in this region and
the high aluminium level in cyst fluid. However, there is still a lack of
clinical studies that relate the antiperspirants' cessation with the treat-
ment of breast cysts.
6|ALUMINIUM AND BREAST CANCER
There has been a big concern regarding the carcinogenicity of ingredi-
ents in cosmetic and personal care products. The media and con-
sumers extensively considered the articles regarding the relation of
aluminium (Darbre, 2009; Linhart et al., 2017) and paraben with breast
cancer (Allam, 2016; Charles & Darbre, 2013) and the relation of talc
powder with ovarian cancer (Booth et al., 1989). Breast cancer is one
of the most prevalent cancer types among women in developed coun-
tries. Chronic exposure to oestrogen through hormone therapy, age
and genetics are among the main risk factors. However, environmen-
tal factors should not be neglected (Linhart et al., 2017;
McGrath, 2003). Due to the high incidence of breast cancer in the
upper outer quadrant (Darbre, 2009; Linhart et al., 2017; Pineau
et al., 2014), the underarm area's cosmetic products are introduced as
a risk factor (Darbre, 2009; Darbre, Mannello, & Exley, 2013; Linhart
et al., 2017; Pineau et al., 2014).
Breast and underarm area and around them are exposed to differ-
ent cosmetic products like antiperspirants, deodorants and breast
firming products once a day or even more. Most of the time, these
products did not wash away and are left on the skin for days; continu-
ous exposure increases the absorption rate and accumulation of cos-
metic products into the skin (Darbre, 2016). The absorption rate may
also increase by shaving those areas because of skin irritation and
scratches. These products' absorption and distribution pathways are
unknown; however, they usually bypass the metabolism pathway
(Darbre, 2009; Darbre, Bakir, & Iskakova, 2013; Darbre, Mannello, &
Exley, 2013).
It has been theorized that aluminium-containing antiperspirants
increase breast cancer risk. It is hypothesized that aluminium salts
reach the mammary glands' epithelium due to the frequent application
of antiperspirants containing aluminium to the underarm (Anane
et al., 1997; Fakri et al., 2006; Guillard et al., 2004). Although it was
stated that cosmetic or personal care products should not be applied
on irritated or broken skin (CFR, 2019), consumers reported applying
these products after shaving or using other hair removal methods.
Therefore, there is a concern regarding the increased absorption rate
of aluminium salts through broken skin (Zakaria & Ho, 2015). It has
been suggested that aluminium can cause gene alteration. Aluminium
binds to the phosphate backbone of DNA, increases the risk of DNA
mistakes and interferes with cell growth. This kind of alterations in cell
growth would result in tumour development. In addition, aluminium
competes with iron in binding to transferrin, enhances oxidative
stress, increases the release and actions of pro-inflammatory cyto-
kines and alters breast tumour cells' ability to migrate, increasing the
rate of metastasis (Wallace, 2015).
The aluminium concentration has been measured in different
parts of cancerous and non-cancerous human breasts to find the rela-
tion between aluminium and breast cancer. The results of these mea-
surements have been summarized in Table 3.
In 2007, researchers reported aluminium in both fat itself and the
defatted breast tissue in a study on breast tissue left after mastec-
tomy. It was mentioned that the amount of aluminium for each
FIGURE 2 Right: The anatomy of a healthy breast. Left: The breast with cysts. In breast cyst, the secretions of the ducts stock in the blocked
or narrowed ducts. It is proposed that the daily application of antiperspirant may cause penetration and accumulation of aluminium in the ducts
and cause cysts
SANAJOU ET AL.7
individual differs in the defatted tissue. The aluminium level in outer
breast regions was higher, which may raise the question that if the
application of aluminium-containing antiperspirant to this region may
cause aluminium accumulation in these regions (Exley et al., 2007).
Nevertheless, this difference in aluminium levels was not observed in
the fat tissue or the whole breast tissue. Thus, further detailed studies
on aluminium concentration in different breast parts should be done
because the fat amount is not the same in all samples. There are dif-
ferences between individuals (Darbre, 2016). The concentration of
aluminium in the nipple aspirate has been measured too. Nipple aspi-
rate fluid reflects the breast's microenvironment, and it is used to
measure the breast cancer biomarkers in women (Mannello
et al., 2009). In patients with breast cancer, aluminium concentration
was higher in nipple aspirate than the healthy person at the same
sampling period (Mannello et al., 2011). The concentration of alumin-
ium in human milk has also been measured, and it was higher than in
blood (Mannello et al., 2009). High concentration could be because of
aluminium's high affinity to the environment, rich in calcium phos-
phate like human milk. Thus human milk, like bone, is assumed to be a
place for aluminium accumulation (Mannello et al., 2009).
Mandriota et al. (2016) have shown that aluminium may be an
environmental carcinogen. They used aluminium chloride in concen-
trations that were found in breast tissue before. These concentrations
fully transformed immortalized normal murine mammary epithelial
cells. These cells showed metastatic and invasive activity compared
with the same cells, which were not treated with aluminium chloride
(Mandriota et al., 2016). This result is consistent with their earlier
paper, where a similarly treated mammary cell line (MCF10A) showed
anchorage-independent growth in vitro (Sappino et al., 2012). The
severity of cancer and its ability to metastasis and invade other tissues
are other factors that should be considered. Aluminium is capable of
increasing the metastatic and invasive character of cancer cells. This
statement was examined by in vivo studies on the MCF-7 human
breast cancer line. Cells that were exposed to aluminium salts for up
to 32 weeks showed metastatic and invasive characteristics. This
effect's exact molecular mechanism is still under investigation (Darbre,
Bakir, & Iskakova, 2013). Animal model studies play an important role
in studying the safety of aluminium-containing antiperspirants. In light
of this, three studies on the mouse and two studies on rats were men-
tioned by SCCS. These studies were based on methodology accepted
for the evaluation of carcinogenicity. Female mice, which received
aluminium-contained drinking water for their whole life, showed leu-
kaemia lymphoma but not males (Schroeder & Mitchener, 1975a).
However, when the same formulation of aluminium was added to the
feed, no toxic results were reported (Oneda et al., 1994). Lung
tumours in the form of malignant or benign were seen in rats with
three different types of aluminium formulation. Mesotheliomas were
reported in a mouse study where aluminium was injected intraperito-
neally (Frash et al., 1992). Thus, considering the result of these stud-
ies, it is not possible to conclude that aluminium is a potential
carcinogen. A list of studies regarding the possible carcinogenic effect
of aluminium has been given in Table 4.
Another character of aluminium that may make it a reasonable
risk factor in breast cancer is being metaloestrogen. Metals have
unwanted effects on the endocrine system. The effect on hormone
levels by metals has a strong influence on overall body status. The
metals that change the oestrogen hormone level are called metal-
loestrogen. The unwanted oestrogenic effects of aluminium, such as
altered protein expression, change in puberty signs and tumour devel-
opment, may be seen (House et al., 2013; Mandriota et al., 2016;
Mannello et al., 2013; Pineau et al., 2014; Rodrigues-Peres
et al., 2013a, 2013b; Wallace, 2015). Overall metalloestrogenic effects
of aluminium may potentiate the breast's changes (Darbre, 2009;
Darbre, Mannello, & Exley, 2013; Wallace, 2015).
Very few epidemiological studies have attempted to address the
exposure to aluminium-containing antiperspirants and the risk of
breast cancer development. Mirick et al. (2002) did the first epidemio-
logical research on the relationship between breast cancer and usage
of aluminium-containing antiperspirant. Their case–control based
TABLE 3 Concentration of aluminium in different breast tissues
Tissue
Aluminium in
malignant
tumour
Aluminium in a
patient with no
cancer
Blood serum
(Mannello
et al., 2009)
-6μg/L (range 3–9)
Human milk
(Mannello
et al., 2009)
-25μg/L (range 11–36)
Defatted breast tissue
(Mulay et al., 1971)
3.75 ppm dry
tissue
Total breast tissue
(Ng et al., 1997)
22.16 ± 1.83 μg/g
dry weight
Total breast tissue
(Pasha et al., 2008)
8.94 μg/g
Breast tissue (Exley
et al., 2007)
4–437 nmol/g
dry wt
Breast tissue (Linhart
et al., 2017)
5.8 (2.3–12.9)
nmol/g
3.8, 2.5–5.8 nmol/g
Breast tissue fat
(Exley et al., 2007)
3–192 nmol/g oil
Breast biopsy (Darbre,
Mannello, & Exley,
2013)
82.8 μg/g (range
12.1–297.0)
19.2 μg/g
(range 1.0–76.1)
Total breast tissue
(House et al., 2013)
0.39 μg Al/g
tissue dry wt
Total breast tissue
(Romanowicz-
Makowska
et al., 2011)
4.40 +/
1.82 μg/g dry
weight
Nipple aspirate fluid
(Mannello
et al., 2011)
268.4 ± 28.1 μg/L 131.3 ± 9.6 μg/L
Breast cyst fluid
(Mannello
et al., 2009)
- Type I 150 μg/L
(range 80–330)
Type II 32 μg/L (range
11–39)
8SANAJOU ET AL.
study on patients diagnosed with breast cancer for 5 years showed no
relation between breast cancer and usage of antiperspirant. By con-
trast, McGrath (2003) performed a study on 437 people diagnosed
with breast cancer, and it was concluded that antiperspirants' usage
increases breast cancer incidence at a younger age. The rate of breast
cancer mainly was higher in those who used antiperspirants fre-
quently on shaved skin. Both these studies suffered from some limita-
tions. The former study was only based on the oral information
collected from patients, and other risk factors have not been consid-
ered in the latter one. Fakri et al. (2006) interviewed 54 cases of
breast cancer and 50 controls. Surprisingly, the number of people in
the control group that used antiperspirants was higher (82%) than
those diagnosed with cancer (51%) (p< 0.05). Thus, this study could
not relate the usage of aluminium-containing antiperspirants with
breast cancer incidence.
In another study based on the case–control method, several
women diagnosed with breast cancer were compared with a healthy
control group. Aluminium concentration in the breast tissue was
higher in those who frequently used underarm products for both
groups. They reported 15–115 nmol/g wet weight aluminium salts in
TABLE 4 List of studies of aluminium regarding its carcinogenicity
Experiment cell line/
animal
Aluminium formulation/
dosage Analysis method Results Reference
- NMuMG cell line
- NOD SCID gamma
(NSG), NOD SCID and
nude mice
- Aluminium chloride
hexahydrate:
100 mM, 30 mM or 10 mM
in Milli-Q H
2
O.
Milli-Q H
2
O solutions were
used for control groups
- The cells were incubated
with different aluminium
chloride concentrations;
then, cells incubated with
100 mM aluminium
chloride hexahydrate
concentration
- In all three strains of mice, a
tumour formed
- Continuous exposure of
mammary epithelial cells to
aluminium enables them to
evade the immunological
barrier
Mandriota
et al., 2016
- Random-bred white
Swiss mice/54 males
and 54 females
- Aluminium potassium
sulfate/5 ppm
Aluminium in drinking water
- Lifetime exposure - Leukaemia lymphoma was
found most frequently in
the female aluminium
group, and aluminium had
a slight tumourigenic
effect (p< 0.05) in female
mice
Schroeder &
Mitchener, 1975a
- B6C3F1 mice - Aluminium potassium
sulfate/
-Aluminium was added to the
diet for 20 months at dose
levels of 1.0, 2.5, 5.0 and
10.0% (w/w)
- Long-term administration of
aluminium potassium
sulfate does not exert
tumourigenic or any other
toxic actions
Oneda et al., 1994
- Non-inbred albino mice - Aluminium oxide/10 mg in
0.5 ml saline/injected
intraperitoneally/twice at
intervals of 1 month
- Lifetime exposure - Mesothelioma seen in the
group of mice treated with
aluminium oxide
Frash et al., 1992
- Random-bred Long–
Evans (BLU: LE) rats
- 52 males and 52 females
- Aluminium potassium
sulfate/5 ppm Al in
drinking water
- Lifetime exposure - Aluminium did not
significantly affect growth
rates in females, but males
were heavier after a year
of age
- Aluminium caused a slightly
elevated incidence of gross
tumours in male rats but
not in females
Schroeder &
Mitchener, 1975b
- Female Wistar rats
- 48 females
- Aluminium oxide,
aluminium silicate, kaolin
- Intratracheal instillations - Statistically significant
increases in benign and/or
malignant lung tumours
were observed with the
types of aluminium
compounds studied
Pott & Roller, 2005
- MCF-7 human breast
cancer cell line
10
4
M aluminium chloride
(AlCl
3
)or10
4
M
aluminium chlorohydrate
(AlChlor)
- Controls contained the
same volume of water
- Short-term (1-week)
exposure
- Long-term (32- to 37-week)
exposure
- These results demonstrate
that long-term exposure to
aluminium can increase
MCF-7 human breast
cancer cells' migratory and
invasive activity
Darbre, Bakir, &
Iskakova, 2013
SANAJOU ET AL.9
cancer tissue. As a result, frequent underarm products on the shaved
skin may increase the amount of accumulated aluminium and pose a
risk of breast cancer (Linhart et al., 2017).
Rodrigues-Peres et al. (2013b) measured aluminium concentration
in central and peripheral parts of breast tumours. They found no sig-
nificant difference between aluminium concentration in the tumour
and the healthy tissue around the tumour. They mentioned no relation
between aluminium and cancer incidence, and aluminium accumula-
tion increases by ageing. The epidemiological studies on the relation
of aluminium and breast cancer have been summarized in Table 5.
7|ALUMINIUM AND AD
AD is clinically characterized by progressive cognitive decline and loss
of ability to perform daily tasks (Crous-Bou et al., 2017). Considering
that life expectancy has increased in the 21st century, AD has become
one of the health-related challenges. There is not enough information
about the cause of this disease; thus, the treatment protocols are just
designed to slow the progress of dementia. It is estimated that more
than 44 million people with AD live around the world, and this num-
ber will be tripled by 2025 (Prince et al., 2013). AD has been catego-
rized into two main types: (i) sporadic, which is more frequent, and
(ii) familial, which is less frequent and mainly related to the genetic
history of the patient (Colomina & Peris-Sampedro, 2017; Lane
et al., 2018). The major pathological changes in AD are amyloid-beta
plaques, neurofibrillary tangles and loss of neurons (Armstrong, 2019;
Colonmina & Peris-Sampedro, 2017; Inan-Eroglu & Ayaz, 2018). The
familial type of AD is associated with three different possible gene
mutations: mutation in genes encoding presenilin 1, presenilin 2 and
amyloid precursor protein. Mutation in these genes changes the amy-
loid precursor protein metabolism, thus resulting in amyloid-beta
plaques (Colomina & Peris-Sampedro, 2017; Inan-Eroglu &
Ayaz, 2018). Moreover, APOE4 genotype is one of the largest risk fac-
tors for AD. Carriers of one ϵ4 allele are two to three times more
under risk for AD. Environmental risk factors, genetic risk factors, age-
ing, head injury, immune system dysfunction, diet, infections and
many other unknown factors contribute to the onset and progression
of sporadic form of AD (Armstrong, 2019; Inan-Eroglu & Ayaz, 2018).
Hence, there is no single factor associated with incidence of AD.
As aluminium is widely dispersed in the environment and is
known for its neurotoxic character, it has been investigated as a risk
factor in developing different central nervous system disorders. Age-
ing increases aluminium concentration and localization in the brain.
Residues of aluminium have been found in post-mortem samples of
brains of patients diagnosed with familial AD (John et al., 2021; Mirza
et al., 2017). These include neurological disorders involving
amyloidogenesis, pro-inflammatory signalling, innate-immune disrup-
tion, and neural degeneration (McLachlan et al., 2020). A high alumin-
ium concentration in the brain would increase amyloid-beta
TABLE 5 List of epidemiological studies on the link between aluminium and breast cancer
Experiment population Analysis method Results Reference
- Women 20–74 age
- Case group: 813 women diagnosed
with breast cancer diagnosed
between 1992 and 1995
- Control group: 793 women without
cancer at the same year interval
- In-person interview:
The frequency of usage of antiperspirants
or deodorants has been investigated.
Also, the study population has been
asked about their shaving habits before
using antiperspirants or deodorants
- The usage of antiperspirant or
deodorant did not increase the risk of
breast cancer
- Shaving habits before application of
them did not increase the risk of cancer
too
Mirick
et al., 2002
- 437 women aged between 31 and
100 years old who diagnosed with
breast cancer between the 1993 and
2001
- Retrospective study using a written
questionnaire sent to surviving female
breast cancer patients mainly focused
on the age that volunteers started
using these products
- The degree of antiperspirant/deodorant
usage and axillary shaving is associated
with the age at which a patient is
diagnosed with breast cancer
McGrath, 2003
- Case group: 54 women diagnosed
with cancer between 2002 and 2003
at a particular hospital
Control group: 50 women with other
problems came to the same hospital
at the same period
- Personal interview using a self-designed
questionnaire
- No link was found between usage of
antiperspirant and breast cancer
- The rate of usage of antiperspirant in
the control group was higher
- The patients who came from a family
with a breast cancer history were
higher than the control group
Fakri
et al., 2006
- Age-matched hospital-based case–
control study:
Women between 20 and 85 years old
Case group: 209 women who were
diagnosed with breast cancer within
5 years
Control group: 209 women who were
not diagnosed with cancer within the
5 years
- Personal interview - It was suggested that there is a relation
between the usage of underarm
cosmetic products and aluminium
concentration in breast tissue and
breast cancer risk
- Mainly in those who reported starting
using these products under the age of
30. The concentration of aluminium in
the interquartile part of the breast was
higher than in the control group
Linhart
et al., 2017
10 SANAJOU ET AL.
formation, inflammation, oxidative stress, apoptosis and gene expres-
sion deficiencies (Inan-Eroglu & Ayaz, 2018). Moreover, several stud-
ies demonstrated the co-localization of aluminium with tau tangles
(Mirza et al., 2017; Perl & Brody, 1980) and amyloid-beta plaques
(Mirza et al., 2017; Yumoto et al., 2009).
Most of the epidemiological studies that investigate the relation
of aluminium with the incidence of AD are focused on exposure to
aluminium from food and water (Flaten, 2001; McLachlan et al., 1996;
Wang et al., 2016) or in the industry (Exley & Vickers, 2014; Wang
et al., 2016; Yang, 2019).
Considering the impact of AD in people's daily lives and the role
of aluminium-containing products as a source of contamination, the
cosmetics and personal care products that contain aluminium too may
act as a risk factor. However, the relation between aluminium-
containing cosmetics and personal care products and AD has not been
investigated thoroughly. The research on aluminium's effect that may
be absorbed to systemic circulation from these products is not
enough. Chronic exposure to aluminium may cause an increased
absorption rate of aluminium through the skin, but further investiga-
tion on the fate of aluminium absorbed from the skin and its possible
contribution to the overall aluminium burden should be done.
8|DISCUSSION AND CONCLUSION
The cosmetic and personal care products that are commercially avail-
able contain possible toxic content like metals. These metals can pose
a risk to human health. Skin is exposed to such products repeatedly
and frequently, which increases the rate of absorption and risk of
unwanted effects regarding the increased level of these metals in the
systemic circulation. The adverse effects of using aluminium-
containing cosmetics and personal care products have been discussed
in recent years. It is proposed that aluminium in these cosmetics may
pose cancerogenic or neurotoxic effects. However, there is no clear
evidence to show that the use of antiperspirants or cosmetics
increases the risk of AD or breast cancer.
The first step to determine the possible toxic effect of aluminium
from cosmetics would be determining the dermal bioavailability of alu-
minium. The studies that were designed to measure dermal absorption
are very few. The biggest limitation to these studies is that it is diffi-
cult to differentiate between the amount of aluminium absorbed from
the skin and other sources of exposure. In these studies, a rare radio-
isotope of aluminium has been used in a specific period. However,
new real-life studies based on daily cosmetics for a more extended
exposure period should be designed. Such a study will reflect the
actual conditions such as different living styles and sweating patterns.
The blood samples that were taken in the epidemiological studies did
not show detectable aluminium levels. However, the urine samples
were used to estimate the dermal bioavailability (0.00192%). As urine
is the excretion pathway for aluminium and more than 50% of alumin-
ium is excreted in the first 24 h of exposure (SCCS, 2020), even if a
person uses aluminium-containing cosmetics every day, significant
accumulation in the body is unlikely.
Regarding the carcinogenic effects of aluminium, the SCCS
reported that aluminium is not a potential carcinogen. There is no evi-
dence of increased cancer risk in non-occupationally exposed persons
(SCCS, 2020). The animals exposed to high doses (up to 850 mg Al/kg
bw/day) of aluminium orally did not prove it to be a carcinogen; thus,
the small amount of aluminium in cosmetics might not cause cancer
too. In addition, the animal studies were not organized well, and the
cosmetics were directly injected into the animal organ instead of test-
ing the dermal exposure. These studies also did not draw a precise
conclusion about the carcinogenicity of aluminium. The case–control
studies investigating the relationship between usage of aluminium and
risk of breast cancer did not support the hypothesis that aluminium
would be a risk factor. Most of these studies are based on question-
naires that the patients themselves answered. The environmental fac-
tors were not included, and some of the studies did not meet the
regulations regarding toxicological testing protocols. As stated before,
antiperspirants work by making a complex on the lining of sweat
glands preventing sweat flow. This insoluble complex, alongside skin's
barriers, prevents aluminium reach to inner layers of skin. Thus, it is
hard to say that aluminium would be a possible risk factor. Even if alu-
minium is absorbed from the skin, the distribution rate can be affected
by the interaction of aluminium ions with other ions like citrate or
phosphate. These ions will change the fate of aluminium.
Another concern about aluminium-containing cosmetics is that
they may be a risk factor in neurological disease. Aluminium is a
known neurotoxin. It accumulates in the brain. Some of the toxic
effects of aluminium in the brain are increasing: the amyloid-beta
plaques and the neurofibrillary tangles. These are the hallmarks of
AD. Thus, aluminium may be considered a risk factor. As there is not
enough knowledge on the dermal absorption of aluminium, it is hard
to estimate if the aluminium in cosmetics will travel to the brain and
cause neurological diseases like AD or autism. Maternal cosmetics
may be a risk factor for autism. Thus, future epidemiological and
in vitro studies would enlighten the role of aluminium-containing cos-
metics as an environmental risk factor in neurological disease.
In conclusion, the studies done till today are a few, and their
results are not consistent and conflicting. Further epidemiological
studies base on a long time and real-life exposure to aluminium
needed to make a clear conclusion about the hypothesis. Biomarkers
that can indicate the fate of aluminium in the body should be used in
future studies. A new methodology is needed to measure the exact
amount of aluminium absorbed from the skin and differentiate it from
other exposure sources. There is a lack of study about aluminium con-
taining toothpaste and lipsticks; thus, these cosmetic and personal
care products should be considered in future studies. Especially in
breast cancer patients, the usage of aluminium-containing lipsticks
and/or toothpaste and cancer incidence should be investigated.
Another source for aluminium might be cosmetics that are made from
natural products. These products are not regulated well, and the
amount of aluminium should be measured in the future.
DATA AVAILABILITY STATEMENT
No data available
SANAJOU ET AL.11
ORCID
Sonia Sanajou https://orcid.org/0000-0002-6751-5266
Gönül S¸ahin https://orcid.org/0000-0003-3742-6841
Terken Baydar https://orcid.org/0000-0002-5497-9600
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