Journal of Trace Elements in Medicine and Biology 28 (2014) 147150

Contents lists available at ScienceDirect

Journal of Trace Elements in Medicine and Biology

journal homepage: www.elsevier.de/jtemb

Review

If exposure to aluminium in antiperspirants presents health risks,

its content should be reduced
Alain Pineau a,1 , Bernard Fauconneau b , Andr-Pascal Sappino c ,
Roger Deloncle d , Olivier Guillard e,,1
a

Universit de Nantes, Facult de Pharmacie, Laboratoire de Toxicologie, 44035 Nantes, France

Universit de Poitiers, Facult de Mdecine et de Pharmacie, Service de Pharmacologie clinique, CHU Poitiers, 86021 Poitiers, France
c
Clinique des Grangettes, Chemin des Grangettes 7, 1224 Chne-Bougeries, Confdration Helvtique, Switzerland
d
Universit de Tours, Facult de Pharmacie, Laboratoire de Toxicologie, 37000 Tours, France
e
Universit de Poitiers, Facult de Mdecine et Pharmacie, 6 rue de la Miltrie, 86034 Poitiers, France
b

a r t i c l e

i n f o

Article history:
Received 19 November 2013
Accepted 9 December 2013
Keywords:
Aluminium
Toxicity
Breast cancer
Antiperspirant

a b s t r a c t
Since aluminium (Al) pervades our environment, the scientic community has for many years raised
concerns regarding its safety in humans. Al is present in numerous cosmetics such as antiperspirants,
lipsticks and sunscreens. Al chlorohydrate is the active antiperspirant agent in underarm cosmetics and
may constitute for Al a key exposure route to the human body and a potential source of damage. An in vitro
study has demonstrated that Al from antiperspirant can be absorbed through viable human stripped skin.
The potential toxicity of Al has been clearly shown and recent works convincingly argue that Al could be
involved in cancerogenic processes. Nowadays, for example, Al is suspected of being involved in breast
cancer. Recent work in cells in culture has lent credence to the hypothesis that this metal could accumulate
in the mammary gland and selectively interfere with the biological properties of breast epithelial cells,
thereby promoting a cascade of alterations reminiscent of the early phases of malignant transformation.
In addition, several studies suggest that the presence of Al in human breast could inuence metastatic
process. As a consequence, given that the toxicity of Al has been widely recognized and that it is not a
physiological component in human tissues, reducing the concentration of this metal in antiperspirants
is a matter of urgency.
2013 Elsevier GmbH. All rights reserved.

Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antiperspirants with aluminium salts: the problem of percutaneous absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antiperspirants with aluminium salts: their repercussions on breast cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

147
148
148
149
149
149
149

Introduction
Up until now and even though US legislators recently proposed a
crackdown on toxic cosmetics [1] the toxicity of ingredients in cosmetics such as heavy metals has been widely ignored. For example,

Corresponding author. Tel.: +33 5 49 45 44 10; fax: +33 5 49 36 62 63.

E-mail address: olivier.guillard@univ-poitiers.fr (O. Guillard).
1
SFERETE (Socit Francophone dEtude et de Recherche sur les Elments traces
Toxiques Essentiels) member.
0946-672X/$ see front matter 2013 Elsevier GmbH. All rights reserved.
http://dx.doi.org/10.1016/j.jtemb.2013.12.002

notwithstanding consumer anxiety with regard to the lead contained in lipstick and its routine use for decades, it was only in
December 2011 that the FDA addressed the subject, afrming that
the amount of lead found in lipstick is very low and does not
pose safety concerns [2]. While this statement is reassuring with
regard to one heavy metal in a given formulation, it nonetheless
appears necessary, rather than running the risk of a human health
hazard, to envision toxicity testing before commercializing a cosmetic. In 2013, Liu et al. [3] studied the presence of other potentially
harmful metals (aluminium, cadmium, chromium and manganese)

148

A. Pineau et al. / Journal of Trace Elements in Medicine and Biology 28 (2014) 147150

in numerous cosmetics such as lip products. They concluded that

cosmetics safety should be assessed not only by the presence of hazardous contents but also by comparing estimated exposures with
health-based references. Moreover, aluminium (Al), a component
of sunscreens/sunblocks, is a pro-oxidant and could signicantly
increase the potential for oxidative damage in the skin [4]. Several works have drawn attention to the toxicity of Al when used in
antiperspirants [5,6].
Since Al pervades our environment, the scientic community
has for many years raised concerns regarding its safety in humans
[7]. Even though there exists no formal characterization of its
health hazards, exposure to Al in industrial settings has led to the
acceptance of an occupational exposure threshold, while for nonoccupational exposure, limits have been set for food and water
intake, though current regulations are primarily based more on
practical than on health-related considerations [8]. The potential
neurotoxicity of Al has been clearly shown. As observed as early
as 1976 by Alfrey et al. [9], its accumulation and overload in the
human can cause fatal encephalopathy in patients with reduced
renal function, and the hypothesis that Al signicantly contributes
to Alzheimers disease is built upon solid experimental evidence
[10]. Whenever aluminium intake is limited, toxicity risk is correspondingly reduced.
Furthermore, aluminium salts, mainly aluminium chlorohydrate (ACH), are the active antiperspirant agents in underarm
cosmetics blocking the sweat ducts by precipitating inside the
eccrine sweat glands to produce insoluble aluminium hydroxide
which then plugs the gland and blocks secretion of sweat onto the
skin surface [11]. In humans, Minshall et al. [12] have shown that
sweat is a major route for excretion of systemic Al; experimentally,
on 20 healthy volunteers following mild exercise, the Al measured
in sweat ranged from 234 to 7192 g/day. This observation calls
into question the practice of disrupting or blocking perspiration
using Al-antiperspirants. At the very least, the latter may constitute a key exposure route to the human body of this metal [5] and
a potential source of damage.
Wulf points out that in 1993, a petition was addressed to the US
Food and Drug Administration concerning the safety of antiperspirants and, more particularly, the risk entailed by absorption of Al
as ACH [5]. The possibly toxic role of this metal in antiperspirants,
and more precisely the risk of adverse effects on human health was
subsequently analyzed at length by Exley [13]. And in 2009, Darbre shed light on the question of antiperspirants/deodorants and
breast cancer [14].

retrospective study limited to a single clinical case, interrogation

on the possible sources of Al was thorough, and the answers given
ruled out either consumption of medication containing sizable
quantities of Al (antacids) or daily exposure (patients profession:
librarian) as a possible cause. Moreover, the measured concentration in this patient (3.88 mol/L) is incompatible with uid intake
from either food or kitchen utensils. The only consequential source
of Al absorption consisted in daily use of an antiperspirant on
shaved skin. Cessation of antiperspirant application ensued without any concomitant modication of the patients life style, and 8
months later, her plasma Al concentration and all clinical symptoms
had returned to normal.
Given signicant variations between individuals and the
absence of specic clinical-biological signs as well as ethical and
cost-based considerations, systematic measurement of plasma
Al concentration in persons with non-medical exposure to nonprescription drugs such as users of Al-based antiperspirants is out
of the question, and that is the main reason why no other biological
data has been found in the literature.
The question to be put forward still revolves around the existence or non-existence of transdermal Al uptake in humans. Fairly
recently, the French health product sanitary safety agency (ANSM)
initiated an in vitro study of Al on the human skin as regards possible
cutaneous penetration on healthy and stripped skin of the different commercial antiperspirant formulas. We conducted this study
in accordance with the applicable Organization for Economic Cooperation and Development in vitro validated alternative test (OECD,
428 in vitro guideline 2004 revised 22 October 2010Guidance Document for the Conduct of Skin Absorption Studies), using a FranzTM
diffusion cell [17]. Results showed that subsequent to testing of the
one-stick formulation, which is the most widely sold product on the
market, transdermal Al uptake six times greater may be observed
in stripped than in normal skin. In fact, the shaved or stripped skin
with micro-cuts onto which antiperspirants are applied may constitute an important entranceway to the organism for Al. This work
[17] lends additional credence to the hypothesis that application of
Al-based antiperspirant may bring about the undesired presence
or accumulation of Al in the tissues of the underarm and surrounding areas, including breast tissues [18]. Moreover, Exley et al. [19]
have measured higher levels of Al from outer than from inner breast
quadrants following use of an antiperspirant in breast tissue.

Antiperspirants with aluminium salts: the problem of

percutaneous absorption

In 2002, however, Mirick et al. [20] found no relationship

between breast cancer and use of Al-based antiperspirants between
a population of breast cancer patients (n = 813) and a group of nonaffected controls (n = 793). In 2003, on the other hand, McGrath
[21] reported with regard to a population of breast cancer patients
that those who used more antiperspirant products on a shaved
underarm tended to be diagnosed with breast cancer at an earlier
age. Objectively speaking, the two studies [20,21] open the way
to constructive questioning, which is sorely lacking in the hastily
afrmative conclusions of Namer et al. [22] in 2008, who expressly
refrain from suspecting any toxic effect emanating from the Al contained in antiperspirants and explicitly abstain from pursuing this
line of inquiry.
And yet, clinical studies have shown a high incidence of breast
cancer in the upper outer quadrant of the breast, thereby providing
further evidence of the role of antiperspirants applied in the adjacent breast region in the development of breast cancer [18]. More
precisely, the Al absorbed through application of antiperspirants
may have consequences on human breast cancer cells by interfering
with the functioning of oestrogen receptors. The studies published

Studies on the subject have nonetheless been few and far

between. Over the past 11 years, the only reported in vivo study in
humans, with 2 healthy volunteers, was performed by Flarend et al.
[15] through a single underarm application of ACH without occlusion bandage using radiolabeled aluminium (26 Al). Having shown
that only 0.012% of applied aluminium was absorbed, the authors
concluded that topical ACH does not signicantly contribute to the
body burden of Al.
But everything was turned topsy-turvy in 2004, when Guillard
et al. [16] reported on the case of a woman with bone pain and
fatigue symptoms. Since all the routine biological tests yielded
normal results, the eld of exploration was extended to minerals, and further examination revealed hyperaluminemia as high
as 3.88 mol/L (Al normal range: 0.10.3 mol/L). Questioning
showed that for 4 years, the woman had been making daily use
of an antiperspirant applied on regularly shaved skin (corresponding all in all to a deposit of 157.3 g of this metal). While ours was a

Antiperspirants with aluminium salts: their repercussions

on breast cancer

A. Pineau et al. / Journal of Trace Elements in Medicine and Biology 28 (2014) 147150

by Darbre in 2005 [23] convincingly demonstrate that Al in the

form of ACH can interfere with the functioning of oestrogen receptors of MCF7 human breast cancer cells through two processes,
namely oestrogen-regulated reporter gene expression and ligand
binding, as has been conrmed in further work by Darbre [18],
Darbre and Charles [24]. Their ndings suggest that Al is a metalloestrogen. Furthermore, Manello et al. [25] have demonstrated
the presence of high levels of Al in breast cyst uid collected from
women affected by gross cystic breast disease and in the nipple
aspirate uid (NAF) collected from women with breast cancer (in
Cancer group, NAF Al: 268.4 28.1 g/L, n = 19; in No Cancer group,
NAF Al: 131.3 9.6 g/L, n = 16; P < 0.0001) [26].
An in vitro study [27] performed on primary normal human
epithelial breast cells (MCF-10A) and on human breast-derived
epithelial cell lines showed that their long-term exposure to aluminium chloride (AlCl3 ) concentrations of 10300 mol/L, i.e. up to
100,000 fold lower than those found in antiperspirants, and in the
range of those recently measured in the human breast [19], results
in loss of contact inhibition and in anchorage-independent growth.
These effects were preceded by an increase of DNA synthesis,
DNA double strand breaks (DSBs), and senescence in proliferating
cultures. In contrast, it had no comparable effects on human keratinocytes (HaCaT) or broblasts (C26Ci), and was not detectably
mutagenic in bacteria. These results suggest that Al is not generically mutagenic but that, similarly to an activated oncogene,
it induces proliferation stress, DSBs, and senescence in normal
mammary epithelial cells, and that long-term exposure to AlCl3
generates and selects for cells able to bypass p53/p21Waf1 mediated cellular senescence.
A recent paper [28] demonstrates for the rst time that exposure to Al (100 M Al chloride or Al chlorhydrate) can also increase
migratory and invasive properties of MCF-7 human breast cancer cells following a long term exposure (32 weeks). These results
suggest that the presence of Al in human breast could inuence
metastatic processes. Now, further researches are necessary to
investigate whether the concentrations of Al measured in the
human breast can lead in vivo to any of the effects observed in
cells in vitro [29]. House et al. [30] recently validated an analytical method of Al in breast tissues that could be used to determine
Al content, thereby contributing to evaluation of the role of Al in
women breast cancer.
All in all, these observations indicate that in humans Al can penetrate the skin and accumulate in breast tissues and that it selectively
interferes with the biological properties of breast epithelial cells,
thereby promoting a cascade of alterations reminiscent of the early
phases of malignant transformation.

Conclusion
Though additional investigations are needed to better dene
the damaging effects of Al in humans, the reported results raise
concerns about the wide use of aluminium in underarm cosmetics
and highlight the importance of recent questioning on the choice
of appropriate models for risk assessment of chemicals [8]. In this
respect, in vitro use of viable human skin is still the most suitable
approach (OECD).
Once these different arguments are taken into account, the
assessment report presented to the ANSM (French health product sanitary safety agency) recommends that Al concentration in
antiperspirants be reduced from 5% to 0.6%. This value is deliberately expressed in Al, so that it can apply to different used forms in
cosmetic products. This new value is calculated from a No Observed
Adverse Effect Level (NOAEL) in a dog study, with a security coefcient of 100.

149

We would also recommend that consumers be informed, on

the packaging, that underarm products containing Al should not
be used, for reasons of human health risk, on damaged skin
after shaving or in the presence of small cuts. The assessment
report was recently transmitted to the European commission
for continent-wide evaluation [31]. Given that the toxicity of Al
has been recognized and that it is not a physiological component in human tissues, these recommendations may constitute
a rst step towards the restriction of this metal in antiperspirants. Moreover, it would make sense to widen the scope of
ongoing discussion to the international community taken as a
whole.
Conicts of interest
The authors: Alain Pineau, Bernard Fauconneau, Andr Pascal
Sappino, Roger Deloncle and Olivier Guillard declare that they have
no conict of interest.
Acknowledgment
The authors thank Christopher Exley (Keele University, UK) for
having critically examined the text.
References
[1] Vogel L. US legislators propose crackdown on toxic cosmetics. CMAJ
2011;183:E116970.
[2] http://www.fda.gov/Cosmetics/ProductandIngredientSafety/
ProductInformation/ucm137224.htm#q8
[3] Liu S, Hammond SK, Rojas-Cheatham A. Concentrations and potential health
risks of metals in lips products. Environ Health Perspect 2013;121:70510.
[4] Nicholson S, Exley C. Aluminum: a potential pro-oxidant in sunscreens/sunblocks? Free Radic Biol Med 2007;43:12167.
[5] Wulf RJ. In: Laden K, Felger CB, editors. Safety of antiperspirant salts. New York:
Marcel Dekker; 1999. p. 21532.
[6] McGrath KG. Apocrine sweat gland obstruction by antiperspirants allowing
transdermal absorption of cutaneous generated hormones and pheromones as
a link to the observed incidence rates of breast and prostate cancer in the 20th
century. Med Hypoth 2009;72:66574.
[7] Exley C. Darwin, natural selection and the biological essentiality of aluminium
and silicon. Trends Biochem Sci 2009;34:58993.
[8] Exley C. Aluminium and medicine. In: Merce ALR, Felcman J, Recio MAL, editors.
Molecular and supramolecular bioinorganic chemistry. New York: Applications
in Medical Sciences; 2009. p. 4568.
[9] Alfrey AC, Legendre GR, Kaehny WD. The dialysis encephalopathy syndrome:
possible aluminium intoxication. N Engl J Med 1976;294:1848.
[10] Tomljenovic L. Aluminium and Alzheimers disease: after a century
of controversy, is there a plausible link? J Alzheimers Dis 2011;23:
56798.
[11] Quartrale RP. In: Laden K, Felger CB, editors. The mechanism of antiperspirant
action in eccrine sweat glands. New York: Marcel Dekker; 1988. p. 89118.
[12] Minshall C, Nadal J, Exley C. Aluminium in human sweat. J Trace Elem Med Biol
2014;28:878.
[13] Exley C. Does antiperspirant use increase the risk of aluminium-related disease,
including Alzheimers disease? Mol Med Today 1998;4:1079.
[14] Darbre PD. Underarm antiperspirants/deodorants and breast cancer. Breast
Cancer Res 2009;11(S5):15.
[15] Flarend R, Bin T, Elmore D, Hem SL. A preliminary study of the dermal absorption
of aluminium from antiperspirants using aluminium-26. Food Chem Toxicol
2001;39:1638.
[16] Guillard O, Fauconneau B, Olichon D, Dedieu G, Deloncle R. Hyperaluminemia
in a woman using an aluminium-containing antiperspirant for 4 years. Am J
Med 2004;117:9569.
[17] Pineau A, Guillard O, Favreau F, Marrauld A, Fauconneau B. In vitro study of
percutaneous absorption of aluminium from antiperspirants through human
skin in the Franz diffusion cell. J Inorg Biochem 2012;110:216.
[18] Darbre PD, Pugazhendhi D, Manello F. Aluminium and human breast diseases.
J Inorg Biochem 2011;105:14848.
[19] Exley C, Charles LM, Barr L, Martin C, Polwart A, Darbre PD. Aluminium in human
breast tissue. J Inorg Biochem 2007;101:13346.
[20] Mirick DK, Davis S, Thomas DB. Antiperspirant use and the risk of breast cancer.
J Natl Cancer Inst 2002;94:157880.
[21] McGrath KG. An earlier age of breast cancer diagnosis related to more frequent use of antiperspirants/deodorants underarm shaving. Eur J Cancer Prev
2003;12:47985.

150

A. Pineau et al. / Journal of Trace Elements in Medicine and Biology 28 (2014) 147150

[22] Namer M, Luporsi E, Gligorov J, Lokiec F, Spielmann M. The use of deodorants/antiperspirants does not constitute a risk factor for breast cancer. Bull
Cancer 2008;95:87180.
[23] Darbre PD. Aluminium, antiperspirants and breast cancer. J Inorg Biochem
2005;99:19129.
[24] Darbre PD, Charles AK. Environmental oestrogens and breast cancer: evidence
for combined involvement of dietary, household and cosmetic xenoestrogens.
Anticancer Res 2010;30:81525.
[25] Manello F, Tonti GA, Darbre PD. Concentration of aluminium in breast cyst uids
collected from women affected by gross cystic breast disease. J Appl Toxicol
2009;29:16.
[26] Manello F, Tonti GA, Medda V, Simone P, Darbre PD. Analysis of aluminium
content and iron homeostasis in nipple aspirate uids from healthy women
and breast cancer-affected patients. J Appl Toxicol 2011;30:2629.

[27] Sappino AL, Buser R, Lesne L, Gimelli S, Bena F, Belin D, et al. Aluminium chloride
promotes anchorage-independent growth in human mammary epithelial cells.
J Appl Toxicol 2012;32:23343.
[28] Darbre PH, Bakir A, Iskakova E. Effect of aluminium on migratory and invasive properties of MCF-7 human breast cancer cells in culture. J Inorg Biochem
2013;128:2459.
[29] Darbre PH, Mannello F, Exley C. Aluminium and breast cancer: sources of exposure, tissue measurements and mechanisms of toxicological actions on breast
biology. J Inorg Biochem 2013;128:25761.
[30] House E, Polwart A, Drabre PD, Barr L, Metaxas G, Exley C. The aluminium
content of breast tissue taken from women with breast cancer. J Trace Elem
Med Biol 2013;27:25766.
[31] http://pro.observatoiredescosmetiques.com/actualite/actualite-cosmetiques/
laluminium-en-cours-devaluation-par-leurope-2013.html [in French].