Aggregated aluminium exposure: risk assessment for the general population

Abstract

Aluminium is one of the most abundant elements in earth’s crust and its manifold uses result in an exposure of the population from many sources. Developmental toxicity, effects on the urinary tract and neurotoxicity are known effects of aluminium and its compounds. Here, we assessed the health risks resulting from total consumer exposure towards aluminium and various aluminium compounds, including contributions from foodstuffs, food additives, food contact materials (FCM), and cosmetic products. For the estimation of aluminium contents in foodstuff, data from the German “Pilot-Total-Diet-Study” were used, which was conducted as part of the European TDS-Exposure project. These were combined with consumption data from the German National Consumption Survey II to yield aluminium exposure via food for adults. It was found that the average weekly aluminium exposure resulting from food intake amounts to approx. 50% of the tolerable weekly intake (TWI) of 1 mg/kg body weight (bw)/week, derived by the European Food Safety Authority (EFSA). For children, data from the French “Infant Total Diet Study” and the “Second French Total Diet Study” were used to estimate aluminium exposure via food. As a result, the TWI can be exhausted or slightly exceeded—particularly for infants who are not exclusively breastfed and young children relying on specially adapted diets (e.g. soy-based, lactose free, hypoallergenic). When taking into account the overall aluminium exposure from foods, cosmetic products (cosmetics), pharmaceuticals and FCM from uncoated aluminium, a significant exceedance of the EFSA-derived TWI and even the PTWI of 2 mg/kg bw/week, derived by the Joint FAO/WHO Expert Committee on Food Additives, may occur. Specifically, high exposure levels were found for adolescents aged 11–14 years. Although exposure data were collected with special regard to the German population, it is also representative for European and comparable to international consumers. From a toxicological point of view, regular exceedance of the lifetime tolerable aluminium intake (TWI/PTWI) is undesirable, since this results in an increased risk for health impairments. Consequently, recommendations on how to reduce overall aluminium exposure are given.

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Archives of Toxicology (2019) 93:3503–3521
https://doi.org/10.1007/s00204-019-02599-z
REVIEW ARTICLE
Aggregated aluminium exposure: risk assessment forthegeneral
population
ThomasTietz1 · ArianeLenzner1· AnnaElenaKolbaum1· SebastianZellmer1· ChristianRiebeling1·
RainerGürtler1· ChristianJung1· OliverKappenstein1 · JuttaTentschert1· MichaelGiulbudagian1·
StefanMerkel1· RalphPirow1· OliverLindtner1· TewesTralau1· BerndSchäfer1· PeterLaux1· MatthiasGreiner1·
AlfonsoLampen1· AndreasLuch1· ReinerWittkowski1· AndreasHensel1
Received: 18 September 2019 / Accepted: 15 October 2019 / Published online: 28 October 2019
© The Author(s) 2019
Abstract
Aluminium is one of the most abundant elements in earth’s crust and its manifold uses result in an exposure of the population
from many sources. Developmental toxicity, effects on the urinary tract and neurotoxicity are known effects of aluminium
and its compounds. Here, we assessed the health risks resulting from total consumer exposure towards aluminium and
various aluminium compounds, including contributions from foodstuffs, food additives, food contact materials (FCM), and
cosmetic products. For the estimation of aluminium contents in foodstuff, data from the German “Pilot-Total-Diet-Study”
were used, which was conducted as part of the European TDS-Exposure project. These were combined with consumption
data from the German National Consumption Survey II to yield aluminium exposure via food for adults. It was found that
the average weekly aluminium exposure resulting from food intake amounts to approx. 50% of the tolerable weekly intake
(TWI) of 1mg/kg body weight (bw)/week, derived by the European Food Safety Authority (EFSA). For children, data from
the French “Infant Total Diet Study” and the “Second French Total Diet Study” were used to estimate aluminium expo-
sure via food. As a result, the TWI can be exhausted or slightly exceeded—particularly for infants who are not exclusively
breastfed and young children relying on specially adapted diets (e.g. soy-based, lactose free, hypoallergenic). When taking
into account the overall aluminium exposure from foods, cosmetic products (cosmetics), pharmaceuticals and FCM from
uncoated aluminium, a significant exceedance of the EFSA-derived TWI and even the PTWI of 2mg/kg bw/week, derived
by the Joint FAO/WHO Expert Committee on Food Additives, may occur. Specifically, high exposure levels were found
for adolescents aged 11–14years. Although exposure data were collected with special regard to the German population, it
is also representative for European and comparable to international consumers. From a toxicological point of view, regular
exceedance of the lifetime tolerable aluminium intake (TWI/PTWI) is undesirable, since this results in an increased risk for
health impairments. Consequently, recommendations on how to reduce overall aluminium exposure are given.
Article Highlights
• Risk assessment of total aluminium exposure from different sources for different age groups.
• Use of data from the European TDS-Exposure project for the estimation of aluminium exposure from foodstuff.
• Comprehensive overview of the toxicological properties of aluminium.
Keywords Aluminium· Dietary exposure· Cosmetics· Food contact materials· Risk assessment· Infants· Children·
Adults· Toxicological overview
Introduction
After oxygen and silicon, aluminium is the third most abun-
dant element and thus the most common metal of the earth’s
crust. Due to its properties, nowadays aluminium is used in
* Thomas Tietz
Thomas.tietz@bfr.bund.de
1 German Federal Institute forRisk Assessment (BfR),
Max-Dohrn-Strasse 8-10, 10589Berlin, Germany
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3504 Archives of Toxicology (2019) 93:3503–3521
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numerous products and technical processes. Hence, it has
become the second most important metallic material after
steel. In 2017, approximately 64 million tons of aluminium
were produced worldwide (IAI 2018). Considering the fre-
quent discussion about the use of aluminium and its toxi-
cological safety, the aim of this study was to estimate the
overall exposure for consumers of different age groups and
to perform a comprehensive risk assessment.
Exposure
Consumer exposure results from a variety of sources. Many
unprocessed foods, such as fruits, vegetables, cereal prod-
ucts, and cocoa, inherently contain aluminium. In addition,
there is a contribution from food additives and articles for
packaging, processing or storage of foods, whether made
of paper, plastic, ceramics or metal. Additional potentially
significant sources of exposure are cosmetics and personal
care products such as antiperspirants, toothpaste, and sun-
screen, from which aluminium can be absorbed either orally
or through the skin.
Absorption distribution metabolism excretion
(ADME)
For the toxic effects of aluminium—apart from the skin irri-
tation effect of some aluminium compounds—the systemi-
cally available amount is decisive. Aluminium compounds
are usually poorly absorbed after oral ingestion (maximum
about 1%) (BfR 2014). Absorption varies by one to two
orders of magnitude depending on the aluminium compound
ingested and other parameters such as pH value, calcium
or iron status as well as the amount ingested or presence
of other substances. For instance, the uptake is increased
by lactate, citrate, and fluoride and significantly reduced
by the presence of silicates or phosphate. The average oral
absorption from food is 0.1% (EFSA 2008). Absorption from
drinking water is slightly higher with approximately 0.3%
(SCHEER 2017). There are only a few studies on the der-
mal uptake of aluminium compounds, particularly in man.
Uptake and urinary excretion were followed in an invivo
study on two individuals (one woman, one man), using the
rare isotope 26Al. The isotope was applied to one armpit of
each person in the form of aluminium chlorohydrate (ACH)
and the excretion was determined for 53days. Based on their
measurements and information on the mean renal excretion
rate of 85% of the absorbed aluminium (Priest etal. 1995),
the authors calculated an average absorption rate of 0.014%
(Flarend etal. 2001). Recently published preliminary data
from another, more comprehensive human toxicokinetics
study (de Ligt etal. 2018) show very similar absorption rates
through intact skin. An invitro study (Pineau etal. 2012)
showed average penetration rates through intact skin of
1.6%, 0.6% and 2.0% for the formulations “deodorant spray”,
“roll-on” and “stick”, respectively (calculated according to
the “Notes of Guidance for the Testing of Cosmetic Ingre-
dients and their Safety Evaluation” of the Scientific Com-
mittee on Consumer Safety of the European Commission
(SCCS 2018) as the sum of the aluminium contents in liv-
ing epidermis, dermis and receptor fluid). With 10.7%, the
penetration rate through skin samples in which the stratum
corneum was damaged by “tape-stripping” was significantly
higher (Pineau etal. 2012). The absorption of aluminium
after uptake by inhalation is not sufficiently investigated
to allow for a comprehensive exposure calculation (EFSA
2008). The existing studies estimate the absorption rate
to 1.5–2%, but cannot reliably prove whether aluminium
absorption took place (only) via the lungs or (also) orally
after mucociliary cleansing (Krewski etal. 2007; Yokel and
McNamara 2001). Direct absorption via the nasal tract has
also been discussed (Yokel and McNamara 2001).
After absorption, aluminium is distributed to all tissues.
Accumulation takes place in almost all tissues, especially
in bones and muscles, in the kidney, but also in the brain
(COT 2013; EFSA 2008; JECFA 2012). The presence of
aluminium in the lungs results primarily from aluminium
compounds inhaled and deposited there.
Unabsorbed orally ingested aluminium is excreted via the
faeces. In contrast, absorbed aluminium is excreted mainly
via urine with a half-life of approximately 1day in a first
phase (JECFA 2012). After aluminium uptake over a longer
period of time, the half-life increases to up to 50years,
which indicates the existence of various aluminium deposits
in the body (EFSA 2008; JECFA 2012).
Acute toxicity
The acute toxicity of aluminium is low. The oral LD50 val-
ues for rats and mice are in the range of 162 and 980mg
Al/kg bw. The high variability is probably due to different
systemically available concentrations of aluminium, since
the absorption rate strongly depends on the respective alu-
minium compound used (EFSA 2008). Some aluminium
compounds are irritating to skin. Irreversible toxic effects
after dermal application, however, have not been described
in the literature.
Genotoxicity andcarcinogenicity
According to the current state of research, aluminium is nei-
ther genotoxic nor carcinogenic (COT 2013; EFSA 2008).
Nevertheless, there is an ongoing debate about a possible
(causal) relationship between the uptake of aluminium, spe-
cifically through the use of aluminium-containing antiperspi-
rants, and the development of breast cancer (see BfR (2014)
for details). Despite a number of studies in which the authors
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3505Archives of Toxicology (2019) 93:3503–3521
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postulated a possible correlation (Darbre 2001; Exley etal.
2007; Mannello etal. 2011; Romanowicz-Makowska etal.
2012), up to now, aluminium could not be proven to be caus-
ative for cancer development. In animal studies even at high
doses of up to 850mg/kg bw/day, no carcinogenic effects
were observed (Oneda etal. 1994), and also two epidemio-
logical case studies failed to establish a connection between
the use of antiperspirants and the incidence of breast cancer
(Fakri etal. 2006; Mirick etal. 2002). After critical analysis
of all published studies on the topic, a French expert group
concluded in 2008 that the use of aluminium-containing
antiperspirants is unlikely to be a risk factor for the devel-
opment of breast cancer (Namer etal. 2008). Instead, other
studies suggest that accumulation of aluminium in diseased
tissue could be the result rather than the cause for cancer
development (Mirick etal. 2002; Ogoshi etal. 1994). This
hypothesis is further strengthened by the findings of other
studies that the amount of other elements, such as iron,
nickel, chromium and lead, is also significantly elevated in
breast cancer tissue (Ionescu etal. 2007; Romaniuk etal.
2017). However, one recent study indicates the respective
aluminium to at least partly originate from the use of anti-
perspirants (Lenhart etal. 2017).
Reproductive toxicity
Oral administration of aluminium in rabbits and dogs led to
a decrease in testes weights and sperm quality. The highest
no adverse effect levels (NOAELs) after oral ingestion in
dogs were between 27 and 88mg/kg bw/day (EFSA 2008).
Detrimental effects on embryos were observed only at rela-
tively high doses (≫ 100mg/kg bw/day) (EFSA 2008; Pi
etal. 2019).
Neurotoxicity
Since aluminium is able to cross the blood–brain barrier, it
can reach and subsequently accumulate in the brain (BfR
2014; Inan-Eroglu and Ayaz 2018; Lukiw etal. 2019;
Mehpara Farhat etal. 2019). At doses above 200mg/kgbw/
day, neurotoxic effects such as behavioural disorders have
been observed in animal experiments even in the absence
of pathological lesions to the brain. Peripheral dysfunctions
were also observed (Martinez etal. 2018). For disturbance
of the vestibulo-ocular reflex in rats of different ages, EFSA
determined a NOAEL of 30mg/kg bw/day (EFSA 2008). In
humans, elevated, toxicologically relevant levels of serum
aluminium led to encephalopathy, as observed for example
at high concentrations of aluminium in water parenterally
administered to dialysis patients or as a consequence of ther-
apeutic intake of aluminium hydroxide (Candy etal. 1992;
Krewski etal. 2007; Seidowsky etal. 2018). In addition to
brain damage, this so-called dialysis encephalopathy is also
characterised by both anaemia and a vitamin D-resistant dis-
order of bone mineralisation (BfR 2007).
The German Permanent Senate Commission for the
Investigation of Health Hazards of Chemical Compounds
in the Work Area (MAK Commission) evaluated several
studies on aluminium concentrations in the urine of human
workers with respect to related cognitive deficiencies (Klotz
etal. 2018). From these, the MAK Commission derived a
NOAEL of 50µg Al/g creatinine. The “background concen-
tration” (biological reference value; BAR value) in urine of
not occupationally exposed humans was estimated to 15µg/g
creatinine (95th percentile) by the MAK Commission (Klotz
etal. 2019).
In the past, neurotoxic effects of aluminium were fre-
quently associated with Alzheimer’s disease (AD) (Inan-
Eroglu and Ayaz 2018; Lukiw etal. 2019; Nie 2018), a
disorder characterised by the accumulation of pathological
amyloid deposits in the brain. These deposits are believed
to originate from the conversion of membrane proteins as a
result of the destruction of nerve cells or cell membranes,
a phenomenon that increases with age. However, various
epidemiological studies failed to connect aluminium levels
in drinking water with the incidence of AD, not the least
due to inconsistencies within the available data. Also, for
elevated levels of aluminium observed in damaged brain
areas (Lukiw etal. 2019; Mold etal. 2019) of AD patients,
it could not be elucidated whether the aluminium deposits
were causative or rather symptomatic of the disease (for a
detailed description, see BfR (2007)).
Furthermore, the neuropathological changes in AD sig-
nificantly differ from those in patients suffering from dialysis
encephalopathy. Therefore, a causal relation between alu-
minium and AD remains questionable (BfR 2007; EFSA
2008; IPCS 1997; JECFA 2012).
Developmental toxicity
For derivation of a tolerable weekly intake (TWI), EFSA
(2008) considered developmental toxicity as the most criti-
cal endpoint. In a number of studies, both young and adult
animals exhibited slowed reflexes, motor disturbances (grip
strength), behavioural changes such as altered escape behav-
iour, as well as delayed puberty and adulthood. In some
cases, learning and memory disorders could also be seen
(Golub and Germann 2001). For the effects described, the
lowest observed adverse effect levels (LOAELs) were in the
range of 50–500mg/kg bw/day. The lowest LOAEL and
NOAEL of 50mg/kg bw/day and 10mg/kg bw/day, respec-
tively, were used by EFSA (2008) as starting values for the
derivation of a TWI.
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3506 Archives of Toxicology (2019) 93:3503–3521
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Organ toxicity
While EFSA chose developmental toxicity for the deriva-
tion of a TWI, JECFA (2012) considered the formation of
concrements in the efferent urinary tract and the subsequent
occurrence of hydronephrosis, which had been reported in
a more recent 12-month study on rat developmental neuro-
toxicity (Poirier etal. 2011), as the most critical endpoints.
The NOAEL was 30 mg/kg bw/day.
Other toxicity
Apart from the toxic effects already described above,
repeated and long-term administration of aluminium in
animal experiments was reported to also lead to unspecific
effects such as reduced body weight gain, slight behavioural
changes (e.g. anxiety or libido), as well as visual changes
such as hair loss or piloerection (EFSA 2008; JECFA 2012;
SCCS 2014). Toxicity to bone was reported in humans and
animals (Klein 2019; Rodriguez and Mandalunis 2018).
To lower the overall exposure of consumers towards alu-
minium, the use or release, respectively, of aluminium is
subject to regulation by various laws: Regulation (EU) No
10/2011 sets a Specific Migration Limit (SML) for the tran-
sition of aluminium from plastic materials into food (simu-
lants) of 1mg/kg food (simulant). In 2013, in consensus
with the industry, the Council of Europe concluded that a
maximum release of 5mg aluminium/kg food from met-
als and alloys is technically achievable and sets this value
as Specific Release Limit (SRL) (EDQM 2013). Regula-
tion (EC) No 1333/2008 sets Maximum Levels (SMLs) for
theuse of various aluminium-containing food additives in
certain foods. Furthermore, Regulation (EC) No 1223/2009
lays down restrictions such as maximum concentrations and
conditions of use for the application of certain aluminium
compounds in cosmetic products. The Directive on the safety
of toys (Directive 2009/48/EC) sets migration limits for
“dry, brittle, powder-like or pliable” (5625mg/kg), “liquid
or sticky” (1406mg/kg), and “scraped-off” (70,000mg/kg)
toy materials, respectively.
Nevertheless, for consumers various sources of alumin-
ium exposure are still present and risk assessment of the
resulting overall exposure is necessary.
Methods
For the risk assessment, the estimated overall exposure was
compared to the health-based guidance values derived by
EFSA and JECFA for the age groups of infants and tod-
dlers (≤ 36 months), children (3–10years), adolescents
(11–14years) and adults (> 14years).
Health‑based guidance values
To take account of the accumulation and very long half-life
of aluminium in the body, instead of a tolerable daily intake
(TDI) EFSA (2008) and JECFA (2012) derived a tolerable
weekly intake (TWI) on the basis of the aforementioned
adverse effects.
EFSA considers developmental neurotoxicity to be the
most critical effect. The LOAELs from various studies are
between 50 and 500mg/kg bw/day, and the NOAELs range
between 10 and 42mg/kg bw/day (EFSA 2008). The lowest
LOAEL/NOAEL originates from a study in mice (Golub
and Germann 2001). EFSA included both the LOAEL of
50mg/kg bw/day and the NOAEL of 10mg/kg bw/day in
the derivation of the TWI. This resulted in a TWI of 1mg/
kg bw/week (EFSA 2008).
Based on a study in rats (Poirier etal. 2011), JECFA con-
siders the formation of concrements in the efferent urinary
tract and the resulting damage to the kidney as the most
critical endpoint. Applying the NOAEL of 30mg/kg bw/day
JECFA (2012) derived a provisional TWI (PTWI) of 2mg/
kg bw/week. This assessment was shared by the Scientific
Committee on Consumer Safety (SCCS 2014) and the Sci-
entific Committee on Health, Environmental and Emerging
Risks (SCHEER 2017).
Exposure assessment
The overall exposure is compared to health-based guidance
values (see above). These were derived for the oral route.
They correspond to a systemic exposure after absorption in
the gastrointestinal tract. Hence, analogous to the procedure
of the Norwegian “Scientific Committee for Food Safety”
(VKM 2013), we decided to first convert the contributions
from non-oral sources via the respective absorption rates
into a systemic exposure and afterwards to calculate an oral
exposure which would lead to the same systemic exposure
(oral exposure equivalents).
Where necessary, the following default body weight val-
ues were applied: 60kg for adults (according to Regulation
(EU) 10/2011), 42kg for adolescents aged 11–14years,
22kg for children aged 3–10years, 12kg for infants aged
1–3years and 6kg for infants up to 12months [all values
are the median according to EFSA (2012)].
Although exposure data were collected with special
regard to the German population, it is also representative
for European and comparable to international consum-
ers, because respective data sources were also taken into
account.
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3507Archives of Toxicology (2019) 93:3503–3521
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Dermal aluminium exposure
The most important non-dietary intake source of aluminium
is dermal exposure from cosmetics, especially antiperspi-
rants, which, according to a previous exposure estimation
(BfR 2014), may reach or even exceed the TWI derived by
EFSA. Exposure estimation is difficult as for most products
robust data on the absorption rate through skin are lacking.
However, in order to still be able to make an estimate, we
used the results of an invivo study (Flarend etal. 2001) on
the dermal absorption of aluminium from antiperspirants,
in which an absorption rate through intact skin of 0.014%
was calculated. For the recalculation into an oral exposure,
the mean rate of 0.1% for the absorption of aluminium from
food estimated by EFSA (2008) is used.
To estimate the quantities of daily usage and the exposed
skin surface for each product, the standard values of the
SCCS “Notes of Guidance for the Testing of Cosmetic
Ingredients and their Safety Evaluation” (SCCS 2018) were
used.
Oral aluminium exposure
Food is presumed to be the most important contributor to
oral exposure (EFSA 2008). Data on food consumption in
adolescents and adults were taken from the German con-
sumption study “Nationale Verzehrsstudie II” (National
Nutrition SurveyII; NVSII) of the Max Rubner Institute
(MRI). The estimation is based on the data from two inde-
pendent non-consecutive 24-h recalls, from 13,926 Ger-
man individuals aged 14–80years (Krems etal. 2006; MRI
2008). The intake estimates were based on the individual
body weights of the respondents.
Data on the aluminium content of foods were taken from
the German pilot total diet study (TDS), which was carried
out within the framework of the European “Total Diet Study
Exposure” (TDS-Exposure) project (http://www.tds-expos
ure.eu) according to the criteria laid down by EFSA/FAO/
WHO (2011) [already described in Kolbaum etal. (2019)].
The selection of foods for the TDS is based on the con-
sumption data of the NVSII and is described in detail by
Dofkova etal. (2016). The food list comprises 246 differ-
ent composite samples (pools), with each pool consisting
of 12 individual samples, and covers 94% of the total food
consumption. Foods from the food groups “Food products
for young population” and “Additives, flavours, baking and
processing aids” were not included, as they are either not
or not significantly consumed by the adult population. Gro-
cery shopping took place between March 2014 and February
2015 in the Berlin area (Germany). Before analysis, the food
was prepared following procedures recorded in the NVS II
orusing typical household recipes from the best-selling rec-
ipe books. After preparation, the subsamples were pooled
and homogenised with inert materials such as stainless steel
or titanium to avoid contamination of the samples. The sam-
ples were analysed in duplicate using ICP-MS (“inductively
coupled plasma mass spectrometry”) at the BfR and at a
contract laboratory. Both laboratories are accredited accord-
ing to DIN EN ISO/IEC 17025. Depending on the respective
matrix and laboratory, the limit of quantification (LOQ) was
between 0.0002 and 0.72mg/kg. The tap water from the
TDS kitchen was analysed separately, and aluminium values
were found to be in a low range of < 0.05mg/kg.
To estimate the long-term dietary intake of aluminium,
the occurrence data from the pilot TDS were linked to the
consumption data of the NVSII. The calculation was car-
ried out using the web-based probabilistic Monte Carlo
Risk Assessment software MCRA (Version 8.2 and 8.2.11,
https ://mcra.rivm.nl) and applying the “observed individual
means” (OIM) model. Results are displayed in mg/kg bw/
week for both the average (mean) and the high-intake con-
sumers (95th percentile, P95), including the correspond-
ing 95% confidence intervals (CIs). For contents below the
respective limit of quantification (< LOQ), two approaches
were used: In the Lower Bound (LB) approach, all values
below LOQ are set to zero, while in the Upper Bound (UB)
approach all values below LOQ are set equal to LOQ. In this
way, the range of the actual exposure is described.
The pilot TDS considered food and consumption only
for adults. Therefore, data from the second French TDS
(ANSES 2011) and the French infant (i)TDS (ANSES 2016;
Sirot etal. 2018) were used for the estimation of the dietary
aluminium intake of infants, toddlers and children. In terms
of methodology, representativeness and topicality, these data
are currently considered as the most appropriate data basis
for assessment of risk for the German population.
The application of aluminium and certain aluminium
compounds as food additives in certain foods is permitted
inthe European Union according to regulation (EC) No
1333/2008. In recent years, the usage of food additives con-
taining aluminium has been restricted significantly. EFSA
(2018) recently re-evaluated substances E520, E521, E522,
E523 and E541 and considered the exposure resulting from
the use of these additives to be negligible and hence of no
safety concern. However, it was recommended that the
combined exposure to aluminium from all the aluminium-
containing food additives should be assessed. In addition, it
should be noted that background exposure to food additives
is already taken into account in the available TDS data by
sampling of industrially producedprocessed foods. Hence,
no additional contribution from food additives was consid-
ered for the overall aluminium exposure.
To estimate the oral exposure to cosmetic products such
as toothpaste and lipstick, the specifications of the SCCS
guideline “Notes of Guidance for the Testing of Cosmetic
Ingredients and their Safety Evaluation” (SCCS 2018)
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3508 Archives of Toxicology (2019) 93:3503–3521
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with regard to the daily amount of use of the products were
applied. Contributions from other sources of exposure, e.g.
food contact materials or pharmaceuticals, were estimated
according to respective evaluations in the literature (BfR
2017b; PEI 2015; Sander etal. 2018).
Aluminium exposure byinhalation
Apart from residential areas in the vicinity of intensive alu-
minium mining, no significant inhalation exposure, e.g. from
ambient air or house dust, is to be expected for consumers
(SCHEER 2017). For the application of antiperspirant aero-
sol sprays, it could be assumed that a part of the spray might
be inhaled. However, in a study on monkeys (Finkelstein and
Wulf 1974), only 0.25% of the applied portion of spray was
inhaled, even though it was sprayed directly into the face.
The portion that reached the lower respiratory tract was even
lower (0.02%). Estimation of the exposure by inhalation is
not possible, because data on the absorption rate via the
lungs are not sufficiently reliable (EFSA 2008). However,
application of the existing data (Krewski etal. 2007; Yokel
and McNamara 2001) for a rough estimation shows that the
combined dermal and inhalative exposure resulting from the
use of antiperspirant aerosol sprays is lower than the expo-
sure from the use of antiperspirant roll-ons or creams. This
is due to the lower aluminium content in sprays in compari-
son to roll-ons or creams (IKW 2016a, b, d) as well as the
lower quantities of daily usage of sprays according to SCCS
(2018). Hence, in the exposure estimation, application of
roll-ons or creams (without inhalative exposure) is used as
worst case assumption.
Results
Estimation ofexposure fromdierent sources
Aluminium content infoods
The main sources of dietary aluminium exposure are sum-
marised in Tables1 and 2 [according to Kolbaum etal.
(2019)].
Table1 shows food in main groups according to EFSA’s
FoodEx2 classification (EFSA 2011). Table2 gives an
overview of the ten food pools with the highest alumin-
ium content. Aluminium was detected in 86% of the 243
samples. Food groups with especially high aluminium
contents are “legumes, nuts, oilseeds and spices” and
“sugars, sweets and water-based sweet desserts”, with an
average aluminium content of 28.5mg/kg and 21.1mg/
Table 1 Mean, minimum
and maximum aluminium
contents from the German pilot
TDS aggregated according
to FoodEX2 level 1 main
groups (in mg/kg fresh weight)
(Kolbaum etal. 2019)
LOQ limit of quantification, LB lower bound, N number of pools in the main food group, UB upper bound
FoodEx 2 level 1
Main food group N% < LOQ Mean Min Max
LB UB
Alcoholic beverages 4 25 0.5 0.5 < LOQ 0.9
Animal and vegetable fats and oils 3 100 0.0 0.1 < LOQ < LOQ
Coffee, cocoa, tea and infusions 8 38 5.2 5.2 < LOQ 35.7
Composite dishes 31 0 1.4 1.4 0.1 6.8
Eggs and egg-products 2 0 0.3 0.3 0.3 0.3
Fish and seafood 19 32 2.5 2.5 < LOQ 38.6
Fruit and fruit products 27 15 1.3 1.4 < LOQ 16.7
Fruit- and vegetable juices and nectars 6 0 1.0 1.0 0.1 2.6
Grains and grain-based products 22 5 2.3 2.3 < LOQ 14.3
Legumes, nuts, oil seeds and spices 10 0 28.5 28.5 0.7 243.5
Meat and meat products 26 8 1.0 1.0 < LOQ 4.1
Milk and dairy products 15 27 0.5 0.6 < LOQ 2.5
Products for non-standard diets, food imitates
and food supplements (here soy and soy
products)
3 0 3.2 3.2 0.4 7.3
Seasoning, sauces and condiments 17 0 1.8 1.8 0.1 5.8
Starchy roots or tubers and products thereof 7 14 1.5 1.5 < LOQ 4.7
Sugar, confectionary and water-based sweet
desserts
12 8 21.1 21.1 < LOQ 116.4
Vegetables and vegetable products 26 15 1.1 1.2 < LOQ 8.0
Water and water-based beverages 5 80 0.1 0.2 < LOQ 0.5
Sum/*mean 243 14 4.1* 4.1*
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3509Archives of Toxicology (2019) 93:3503–3521
1 3
kg, respectively. The high contents found in these food
groups are mainly due to the pools “spices” or cocoa-con-
taining products, such as “bitter chocolate” and “pralines”
(Table2). For all other food groups the concentrations
range between 0.1 and 5.2mg/kg. No aluminium was
detected in the group “animal and vegetable fats and oils”.
Dietary aluminium intake fortheGerman adult population
The mean aluminium intake for the adult population
(14–80years) in Germany ranges between 0.18mg/kg bw
(LB) and 0.21mg/kg bw (UB) per week (Table3). For
highly exposed persons (P95), the weekly aluminium intake
ranges between 0.42mg/kg bw (LB) and 0.44mg/kg bw
(UB). There are no significant differences between age and
gender groups. These intake values correspond to 18–21%
(mean) and 42–44% (P95) of the EFSA-derived TWI of 1
mg Al/kg bw/week.
With 11% of total aluminium intake, the main contri-
bution results from instant tea beverages. Other relevant
sources of exposure are mixed vegetable salads, tea bev-
erages, bitter chocolate and multigrain bread (see Fig.1).
Other cocoa and chocolate products also contribute to the
overall aluminium intake (not shown separately). Hence, the
data presented here are in line with the results of a study on
aluminium intake via cocoa and chocolate products, which
was carried out in 2017 on the basis of data from the Ger-
man food monitoring programme (BfR 2017a).
Due to the high consumption in combination with the
LOQ, natural mineral water appears to be among the main
contributors of aluminium intake in the UB approach. How-
ever, aluminium content was below the detection limit in the
respective samples. In general, there is only a slight differ-
ence between the LB and UB approach with respect to the
main intake sources. Contributors are diversely distributed
over different food groups and cannot be assigned to a spe-
cific consumption pattern.
The estimated aluminium intake through food in the Ger-
man adult population [0.18–0.21mg/kgbw/week (mean);
0.42–0.44mg/kgbw/week (P95)] is in good accordance
with other European data. The aluminium intake of adults
in France was estimated to be on average at 0.28mg/kgbw/
week and at 0.49mg/kgbw/week for high-intake consum-
ers (ANSES 2011; Arnich etal. 2012). The slightly higher
values result from the applied middle bound approach in
combination with significantly higher LOQ. In a recent study
for the Italian adult population, a mean intake of 4.1mg/day
(corresponding to 0.48mg/kg bw/week; bw = 60kg) was
estimated (Filippini etal. 2019). Data from EFSA (2008) as
well as studies from non-European countries such as Aus-
tralia and New Zealand (FSANZ 2011, 2014; MPI 2016),
Hong Kong (CFS 2013) or China (Liang etal. 2019) show
slightly or significantly higher aluminium intakes. However,
due to older data (EFSA 2008) or differences in the eating
Table 2 Aluminium content of the ten food pools with the highest
aluminium content in the German pilot TDS (mg/kg fresh weight)
a Large deviation (31.4mg/kg and 201.3mg/kg) in the duplicate anal-
ysis
TDS Pool
(corresponding FoodEx2 Food group) Aluminium
content in
mg/kg
Spices
(Legumes, nuts, oil seeds and spices) 243.5
Bitter chocolate (incl. filled)
(Sugar, confectionary and water-based sweet des-
serts)
116.4a
Syrups
(Sugar, confectionary and water-based sweet des-
serts)
70.0
Mussels
(Fish and seafood) 38.6
Cocoa powder and beverage powder
(Coffee, cocoa, tea and infusions) 35.7
Pralines
(Sugar, confectionary and water-based sweet des-
serts)
31.5
Oilseeds
(Legumes, nuts, oil seeds and spices) 30.4
Dried vine fruits
(Fruit and fruit products) 16.7
Muesli and similar
(Grains and grain-based products) 14.3
Chocolate spreads
(Sugar, confectionary and water-based sweet des-
serts)
12.9
Table 3 Long-term aluminium
intake through food for the
German adult population
(14–80years) and resulting
exhaustion of the TWI/PTWI;
data taken from the NVSII and
the German pilot TDS
bw body weight, CI 95% confidence interval, LB Lower bound, UB Upper bound, (P)TWI (provisional)
tolerable weekly intake
Aluminium intake in mg/kg bw/week Exhaustion of the EFSA-
TWI/JECFA-PTWI
LB CI UB CI LB UB
Mean 0.18 (0.177; 0.181) 0.21 (0.203; 0.207) 18%/9% 21%/11%
Median 0.14 (0.138; 0.143) 0.17 (0.166; 0.169) 14%/7% 17%/9%
95th percentile 0.42 (0.404; 0.427) 0.44 (0.428; 0.449) 42%/21% 44%/22%
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3510 Archives of Toxicology (2019) 93:3503–3521
1 3
habits or methods for exposure estimation, these data are not
directly comparable to the data presented herein.
Dietary aluminium intake forinfants, toddlers andchildren
The results from the French TDS and iTDS (ANSES 2011,
2016; Sirot etal. 2018), covering the age between < 1month
and 14years, are presented in Tables4 and 5. The mean alu-
minium intake increases from 0.21 to 0.37mg/kg bw/week
(LB) in the first 36months. In the 90th percentile, the intake
increases from 0.43 to 0.61mg/kg bw/week (LB). According
to the authors, the increase results from the stepwise inclu-
sion of additional food products in the daily diet (Sirot etal.
2018). Infant formula is the main source of aluminium intake
until the 4thmonth (85%). Afterwards, follow-on formulas,
ready-to-eat vegetable meals for children, and vegetables
(excluding potatoes) become increasingly important (> 10%)
(Sirot etal. 2018). The resulting average dietary alumin-
ium intake corresponds to 21–37% of the TWI derived by
EFSA. High-intake consumers take up 43–61% of this TWI
(Table4).
Children aged 3–6years have the highest dietary alumin-
ium intake. Exposure for this age group is at 0.64mg/kg bw/
week (mean) and 1.02mg/kg bw/week (P95), corresponding
to 64% and 102%, respectively, of the TWI derived by EFSA
(Table5). With increasing age, aluminium intake gradually
decreases to 0.34mg/kg bw/week (mean) and 0.58mg/
kgbw/week (P95). Vegetables (excluding potatoes), milk-
based desserts and pasta are the main sources of aluminium
intake among children (6–9%).
The data from the second French TDI and the iTDS are
in good accordance with another recent study on infants and
Fig. 1 Main contributors of dietary aluminium exposure in the German adult population (14–80years) on the basis of NVSII and the German
pilot TDS
Table 4 Long-term aluminium intake for infants and toddlers aged
1–36months through food as estimated in the French ‘Infant TDS’
(iTDS) and resulting exhaustion of the TWI/PTWI (ANSES 2016;
Sirot etal. 2018)
bw body weight, LB lower bound, UB upper bound, (P)TWI (provi-
sional) tolerable weekly intake
Age in months Mean 90th percentile
LB UB LB UB
Aluminium intake in mg/kg bw/week
1–4 0.21 0.22 0.43 0.43
5–6 0.32 0.32 0.52 0.52
7–12 0.35 0.36 0.55 0.56
13–36 0.37 0.39 0.61 0.62
Exhaustion of the EFSA-TWI/JECFA-PTWI
1–4 21%/11% 22%/11% 43%/22% 43%/22%
5–6 32%/16% 32%/16% 52%/26% 52%/26%
7–12 35%/18% 36%/18% 55%/28% 56%/28%
13–36 37%/19% 39%/20% 61%/31% 62%/31%
Table 5 Long-term aluminium intake for children aged 3–14 years
through food as estimated in the second French TDS (ANSES 2011)
and resulting exhaustion of the TWI/PTWI
bw body weight, (P)TWI (provisional) tolerable weekly intake
a Middle Bound approach
Age in years Aluminium intake in
mg/kg bw/weekaExhaustion of the EFSA-
TWI/JECFA-PTWI
Mean 95th percentile Mean 95th percentile
3–6 0.64 1.02 64%/32% 102%/51%
7–10 0.49 0.82 49%/25% 82%/41%
11–14 0.34 0.58 34%/17% 58%/29%
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3511Archives of Toxicology (2019) 93:3503–3521
1 3
toddlers conducted by the Austrian agency for health and
food safety (AGES 2017).
The above-mentioned estimates for infants do not con-
sider that alternatives for infant formulas (e.g. soy-based or
hypoallergenic formula) may contain much higher alumin-
ium contents. For example, Dabeka etal. (2011) found in
an extensive study of 473 different infant formulas and sub-
stitutes in Canada on average about fourfold higher alumin-
ium content in soy-based formulas (733µg/kg) compared to
milk-based formulas (177μg/kg). Other modifications, such
as amino acid pattern adjustments, hypoallergenic or lactose-
free milks, also show higher aluminium values. Chuchu etal.
(2013) found in 20 products sampled in the UK on average
3.6-fold higher levels in soy-based infant formula (706μg/
kg) (N = 2) compared to the milk-based diet (195μg/kg)
(N = 18). All values refer to the conversion to reconstituted
powder. Comparing data from the German TDS pilot with
regard to aluminium contents in soy drinks (1.8 mg/kg) and
cow milk (< LOQ) or soy yoghurt (0.4mg/kg) and cow milk
yoghurt (< LOQ), respectively, indicates that the respective
infant products in Germany may also contain higher alu-
minium contents if they are soy based.
EFSA (2008) also concluded that adapted infant formu-
las, such as soy-based or hypoallergenic products, result
in significantly higher exposure. In contrast, the modelled
aluminium intake for 3 months old, exclusively breastfed
infants is with 0.04mg/kg bw/week (average consumption)
and 0.06mg Al/kg bw/week (high-intake consumption),
respectively (EFSA 2008; JECFA 2007), much lower than
the intake of children fed with adapted products or infant
formula (0.21–0.52mg/kg bw/week in the first 6months,
compare Table4). However, to model the data for breast-
fed infants, only one study from 1989 is used, which only
reported contents below the limit of detection (< 50μg/l).
Table6 summarises more recent data on aluminium content
in human milk. The results range from 100% below the limit
of detection in France to a maximum of 380μg/l milk for
Austrian women. On average, values between 13 and 67μg/l
as well as high standard deviations are reported. Hence, the
data used by EFSA and JECFA lead to a rational, though not
especially conservative exposure estimation.
Dietary aluminium intake summarised
Figure2 shows the cited French (ANSES 2011, 2016; Sirot
etal. 2018) and the evaluated German data for the long-term
dietary intake of aluminium in different age groups used for
the risk assessment presented herein (data from Tables3,
4, 5). In the first months of life, aluminium intake increases
steadily with increasing variability in food choices. It must
be taken into account that only non-breastfed children were
included. Aluminium intake via breast milk is significantly
lower than via intake via infant food. From the age of 6years
on, the aluminium intake is decreasing. Adults have the low-
est exposure in relation to their body weight. There is a large
variation in aluminium intake from food, which could be
attributed to variable background levels, use of food addi-
tives, food contact materials and eating habits. Hence, for
brand loyal consumers of products with high aluminium
contents and for consumers of adapted infant formula, higher
aluminium intakes might result.
Aluminium intake throughfood contact materials (FCM)
Materials and articles which are used for production, pack-
aging, cooking, eating and storage of food can release alu-
minium into the food. EFSA (2008) estimated the weekly
aluminium exposure to be higher for elderly people living in
care facilities due to the assumed more frequent consump-
tion of food from aluminium menu trays (average consum-
ers: 0.57 compared to 0.41mg Al/kg bw/week; high-intake
consumers 1.14 compared to 0.88mg Al/kg bw/week). Sig-
nificant transition of aluminium into food is to be expected
above all when uncoated aluminium articles are used in con-
nection with acidic, basic or salty foodstuffs. In this context,
the BfR had reported high aluminium contents in lye biscuits
Table 6 Aluminium content in breast milk
n.s. not specified, LOD limit of detection
a Standard deviation
Country Year of sampling Samples Content References
Germany (Lower Saxony) 2016 19 Mean: 20μg/l
Range: < LOD to 40μg/l
LAVES (2017)
Taiwan 2008 45
45
Mean: Colostrum: 56 ± 23aμg/l
Ripe milk: 13 ± 6aμg/l
Chao etal. (2014)
Austria (Graz) n.s. 27 Median: 67μg/l
Range: < 10 to 380μg/l
Krachler etal. (2000)
Spain n.s. 45 Mean: 23 ± 10a μg/l
Range: 7 to 42μg/l
Fernandez-Lorenzo etal. (1999)
France n.s. 17 Mean: < LOD (8μg/l) Biego etal. (1998)
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3512 Archives of Toxicology (2019) 93:3503–3521
1 3
(BfR 2002) and apple juice (BfR 2008). In 2017, the BfR
investigated menu trays made of uncoated aluminium for
the release of this metal into acidic foods such as strained
tomatoes, sauerkraut juice and apple puree during normal
cooking and keeping warm procedures (cook & chill), and
calculated the additional contribution to the weekly exposure
of an adult when eating a meal (200g) per day at 0.5mg Al/
kg bw/week (BfR 2017b; Sander etal. 2018). Recent results
support these findings (Ertl and Goessler 2018). Data on
aluminium release from FCM made of ceramics (Beldì etal.
2016) or paper and board (BVL 2019) suggest that these
FCM might be an additional source of aluminium exposure.
Aluminium intake throughlipsticks
Lipsticks may contain colour pigments which contain alu-
minium or were produced by aluminium salt precipitation
(“aluminium lakes”). Liu etal. (2013) analysed the alu-
minium content in 32 lipsticks. The maximum content was
27,000mg Al/kg, the median 4431mg/kg. In 11lipsticks/
lip gloss, the “Norwegian Institute for Air Research” deter-
mined aluminium contents of up to 28,000mg/kg (NILU
2011). The median was 7700mg/kg. The Austrian AGES
(2017) has examined 22 samples of lipsticks, incl. lip balm.
The maximum content was 19,000mg/kg and the mean at
about 10,000mg/kg.
For lipsticks, only the oral route is relevant for the expo-
sure assessment. Dermal uptake is expected to be negligible.
For the calculation of the systemic exposure, the assumption
that the whole amount applied to the lips is swallowed is
considered to be conservative and covers a possible der-
mal exposure. According to the guideline of the SCCS
(2018), about 0.057g lipstick is applied daily. Based on
the reported mean/median aluminium contents, the average
weekly intake for an adolescent or adult (bw = 60kg) is
0.029–0.066mg Al/kg bw/week (mean or median alumin-
ium contents reported in the studies cited above were used
for the calculation). However, application of the lipstick with
the highest reported aluminium content of 28,000mg/kg
(NILU 2011) would result in an intake of 0.19mg Al/kg
bw/week. For children between 11 and 14years with a bw
of 42kg (see EFSA (2012)), the average exposure would be
0.042–0.073mg Al/kg bw/week, while the lipstick with the
highest aluminium content would lead to a systemic expo-
sure dose of 0.27mg Al/kg bw/week.
Aluminium intake throughtoothpaste
In toothpaste, the use of aluminium fluoride up to a concen-
tration of 1500ppm (0.15% based on the fluoride content)
is permitted according to the European Cosmetics Regula-
tion (Regulation (EC) No 1223/2009), but data on the actual
use are scarce. However, the vast majority of products seem
to contain sodium fluoride instead of aluminium fluoride.
Hence, a relevant aluminium uptake can be expected only
from the use of so-called “whitening” toothpastes, which
may contain aluminium oxide or hydroxide as abrasives.
According to a study by the predecessor institute of the Nor-
wegian Food Safety Authority in 1997, the median value
of the aluminium content is 4.5% (VKM 2013). Studies by
AGES (2017) on 15 samples of toothpaste showed a high
diversity of the results, with a mean content of 0.9% and a
median of only 0.02%. The highest content found was 3.9%.
According to SCCS (2018), about 2.75g of toothpaste is
used per day, of which about 138mg (5%) is swallowed.
For an adult, an aluminium content of 0.02% AGES (2017)
would lead to an exposure of 0.003mg Al/kg bw/week. For
children between 11 and 14years, the exposure would be
Fig. 2 Long-term aluminium
intake in different age groups.
Data basis: French iTDS, sec-
ond French TDS (ANSES 2011,
2016; Sirot etal. 2018) and Ger-
man pilot TDS. Upper bound
estimates for the age group
1–36months and 14–80years
and middle bound estimates
for the age group 3–6years,
respectively
0.00
0.20
0.40
0.60
0.80
1.00
1.20
1-4
month
5-6
month
7-12
month
13-36
month
3-6
years
7-10
years
11-14
years
14 - 80
years
French
iTDS
2nd French
TDS
German
pilot TDS
Aluminium exposure in mg/kg bw/week
Average consumer High consumer
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3513Archives of Toxicology (2019) 93:3503–3521
1 3
0.005mg Al/kg bw/week. In contrast, the content of 4.5%
aluminium determined by the VKM (2013)would result in
an oral exposure of 0.72mg Al/kg bw/week for adults and
1.0mg Al/kg bw/week for children.
Dermal uptake ofaluminium throughantiperspirants
In most cases, the active ingredient of antiperspirants is
ACH (roll-ons and sprays). IKW (2016a, b, c, d) reports
ACH concentrations of up to 30% for antiperspirant creams
and pump sprays, corresponding to an aluminium content
of approx. 7.5%. AGES (2017) tested 25 antiperspirants and
two deodorants for their aluminium content. As expected, the
deodorant samples did not contain any aluminium. The anti-
perspirants contained between 0.2 and 5.8% aluminium, with
an average content of 2.8%. A study of the Bavarian State
Office for Health and Food Safety (LGL 2018) on 69 sam-
ples resulted in aluminium contents between 0.2 and 5.7%.
The mean value for roll-on products was 2.9%. According
to SCCS (2018), approximately 1.5g antiperspirant is used
per day. For an average aluminium content of 2.8% (AGES
2017) this would result in an oral exposure equivalent of
0.69mg/kg bw/week for adults and 0.98mg Al/kg bw/week
for children between 11 and 14years, respectively. For the
antiperspirant with the highest measured aluminium content
(5.8%, AGES 2017), the exposure equivalent would even be
1.43mg Al/kg bw/week for adults and 2.04mg Al/kg bw/
week for children.
Dermal uptake ofaluminium throughsunscreen
Nicholson and Exley (2007) determined the aluminium con-
tent in several sunscreen products and reported the highest
content to be above 0.1% (w/w). AGES (2017) examined 14
samples of sunscreens. The aluminium content in 5 samples
was below the LOQ. The average content of the remain-
ing samples was 0.1%, with a maximum content of 0.8%.
According to SCCS (2018) and RIVM (2006), a daily appli-
cation of 18g of sunscreen is assumed on 25days/year. For
the average aluminium content of 0.1%, an exposure equiva-
lent of 0.02mg Al/kg bw/week would result for adults. For
the sunscreen with the highest measured aluminium content
(0.8%), the exposure equivalent is 0.16mg Al/kg bw/week.
According to SCCS (2018), the ratio of body surface area to
body weight is not constant across all age groups. The ratio
for 1-year, 5-year and 10-year-old children is 1.6, 1.5 and
1.3 times higher than the ratio for adults. Thus, maximum
exposure equivalents for these age groups of 0.26, 0.24 and
0.21mg Al/kg bw/week, respectively, are calculated.
Other sources ofexposure
Aluminium is a necessary adjuvant in certain vaccines as
well as a main component of certain drugs to neutralise gas-
tric acid in heartburn or inflammation of the upper gastric
tract (antacids). The “Paul Ehrlich Institute” (PEI) estimates
that the cumulative intake of aluminium from all aluminium-
containing vaccines recommended in Germany in the first
2years of life (2–5.8mg intramuscular) is in the range of
the systemic exposure, which can be estimated from toler-
able dietary intake based on European or WHO limits (TWI/
PTWI) for the same period (PEI 2015). Hence, an exposure
equivalent of 1–2mg Al/kg bw/week was calculated for
children ≤ 2years.
Antacids may contain aluminium oxide or -hydroxide,
-phosphate or aluminosilicates (RoteListe 2018). According
to the “Model Lists of Essential Medicines” (WHO 2007),
aluminium-containing antacids contain about 500mg of alu-
minium hydroxide in tablet form or 320mg (per 5ml) in gel
form. This would correspond to 173mg or 111mg alumin-
ium per application. For an adult, this would correspond to
an exposure of 1.85–2.88mg/kg bw per application. Hence,
for a day on which a person has to take the respective drugs,
an uptake of up to 33mg Al/kg bw can result (Fischer 2014).
This single intake would correspond to the sum of daily
tolerable intakes over a period of more than 16weeks, even
if the higher PTWI-value derived by JECFA is used as a
basis. However, the resorption rate in the gastrointestinal
tract is significantly lower with a single administration of
high doses of aluminium than with a continuous intake of
low doses; aluminium from aluminosilicates is generally of
very low bioavailability.
Other drugs contain aluminium, too, for example alu-
minium stearate as an excipient in tablet manufacture [up to
0.5–5%, (Hunnius 2014)] or for antidiarrheal drugs. Another
possible source of exposure for aluminium may be raw
materials in cosmetic products containing water-insoluble
aluminium compounds such as minerals, glass and clay/alu-
mina, carbohydrate compounds or fatty acid salts. Insoluble
minerals, glass and clay/alumina are added to cosmetic prod-
ucts as bulk ingredients, colour pigments and mild abrasives.
However, there is not enough data to estimate the exposure
from these sources.
There are also no representative quantitative data avail-
able on the aluminium content in toys. According to inves-
tigations by the German official control laboratories, which
check compliance with the limits from Directive 2009/48/
EC (see above), none of the analysed samples (90 in total)
exceeded these limits and, hence, toys have “harmless alu-
minium contents” (Lubecki 2014). However, migration
from toys even below the current legal limit may contribute
significantly to the overall aluminium exposure, especially
for infants and toddlers. Currently, it is intended to lower
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3514 Archives of Toxicology (2019) 93:3503–3521
1 3
the current migration limitsin Directive 2009/48/EC by
approx. 60% (https ://eur-lex.europ a.eu/legal -conte nt/EN/
TXT/?uri=pi_com:Ares(2019)89217 ), to adapt them to the
current state of knowledge according to SCHEER (2017).
Estimation ofaggregated exposure fordierent age
groups
The relevant exposure contributions for different age groups
are summed up below (Tables7, 8). To calculate expo-
sure for “normally exposed individuals”, the exposure to
aluminium for normal food-consumers (mean or median,
depending on the study) was used. Depending on the age
group, additional contributions from sunscreens, lipsticks,
toothpaste, antiperspirants and vaccines were considered.
Additional contributions from the use of abrasive toothpaste
and FCM were not taken into account. For the calculation of
the exposure for “highly exposed individuals”, the exposure
values for high food-consumers (usually the 95th percentile)
were used. In addition to the contributions for “normally
exposed individuals”, usage of aluminium-containing FCM
and abrasive toothpaste was taken into account.
For infants, toddlers and children until 10years of age,
abrasive toothpaste, lipsticks and antiperspirants were not
considered, because the use of these products in these age
groups is expected to be very low. Vaccination was only
considered as relevant source of exposure for infants and
toddlers until the age of 24months. For breastfed children,
no additional intake from FCM was taken into account.
For infants, aluminium exposure is lowest if the children
are breastfed (Table7). Without consideration of vaccines,
even for breastfed children with high consumption the maxi-
mum exposure is 0.3mg/kg bw/week. After weaning, the
exposure is significantly higher due to higher aluminium
content in the diet as well as possible additional contribu-
tions from FCM. For highly exposed infants and toddlers,
the maximum exposure is 1.4mg/kg bw/week when vaccina-
tion is not considered.
For age groups other than infants and toddlers, the weekly
aluminium exposure is lowest for children between 3 and
10years (Table8). This is due to the possible high impact
of antiperspirants and abrasive toothpaste in the older age
groups. If only the non-avoidable contributions from food
and cosmetics are considered, the weekly aluminium expo-
sure is significantly lower and does not differ much between
the different age groups.
For not occupationally exposed adults, the MAK Com-
mission estimated a 95th percentile of renal aluminium
excretion of 15µg/g creatinine (Klotz etal. 2019). A rough
estimate of the daily aluminium intake (as oral exposure
equivalents) can be calculated, if the following assumptions/
standard values are applied:
• Urinary aluminium concentrations in the studies resulted
from continuous and relatively constant aluminium
intake over a long time period.
• Between 80 and 90% of the absorbed aluminium is
excreted via urine (Priest etal. 1995).
Table 7 Total weekly aluminium exposure for infants and toddlers (≤ 36months), calculated as oral exposure equivalents
Bold indicates the sum of the exposure estimation which is used for the risk assessment later on
Exposure-contribution Weekly aluminium exposure in mg Al/kg bw/week
Breastfed
children (EFSA
2008)
1–6months (not breastfed)
(ANSES 2016; Sirot etal.
2018)
7–24months (ANSES
2016; Sirot etal. 2018)
25–36months (ANSES
2016; Sirot etal. 2018)
(1) Food, average consumers 0.04 0.21–0.32 0.35–0.39 0.35–0.39
(2) Sunscreens 0.02–0.26
Sum normally exposed persons without
vaccination ((1) + (2)) 0.06–0.3 0.2–0.6 0.4–0.7 0.4–0.7
(3) Food, high-intake consumers 0.06 0.43–0.52 0.55–0.62 0.55–0.62
(4) FCM (containing aluminium) – 0.50 0.50 0.50
Sum highly exposed persons without vac-
cination ((2) + (3) + (4)) 0.08–0.3 1.0–1.3 1.1–1.4 1.1–1.4
Other contributions
(5) Vaccines 1–2 –
Sum normally exposed persons after
start of vaccination at 2months
((1) + (2) + (5))
1.1–2.3 1.2–2.6 1.4–2.7 –
Sum highly exposed persons after
start of vaccination at 2months
((2) + (3) + (4) + (5))
1.1–2.3 2.0–3.3 2.1–3.4 –
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3515Archives of Toxicology (2019) 93:3503–3521
1 3
• Creatinine excretion is between 15 and 25mg/kg bw/day,
or 0.9–1.5g/day for an adult with a body weight of 60kg,
respectively (Inker and Levey 2014).
• Mean oral absorption rate is 0.1% (EFSA 2008).
Applying these assumptions, the aluminium intake (as
oral exposure equivalents) for highly exposed adults (95th
percentile) is calculated to 1.8–3.3mg/kg bw/week. Despite
the rough assumptions, this value is in good accordance with
the exposure estimation described above (Table8).
Discussion
For risk characterisation, the respective weekly aluminium
exposure for the different age groups is compared to the
EFSA-derived TWI of 1mg/kg bw/week (based on devel-
opmental neurotoxicity) and the JECFA-derived PTWI of
2mg/kg bw/week (based on impairments of the urinary tract
and kidney), respectively (Table9).
Risk assessment forinfants andtoddlers
The EFSA-derived TWI is exhausted or in some cases sig-
nificantly exceeded for infants and toddlers (≤ 36months),
regardless of the type of diet (Table9). The JECFA-derived
PTWI can also be exhausted or exceeded in this population
group (see also BfR (2012)).
A significant part of the exposure results from the vac-
cinations recommended by the WHO and the Robert Koch
Institute (RKI 2017). However, these vaccinations have
a high health benefit, both for the individual and for the
population as a whole (RKI 2016). Moreover, they only
provide a relevant contribution to aluminium exposure in
the first 2years of life and not the whole of life. Clinical
and epidemiological studies also show that exposure to
aluminium from vaccines does not pose a health risk (PEI
2015; RKI 2016; WHO 2012). However, the additional
exposure of infants and young children to aluminium via
food and FCM should be as low as possible. Exposure
to aluminium in breast milk diets is significantly lower
than in other diets (BfR 2012, Table7). Particularly cer-
tain adapted diets (e.g. soy based, lactose free, hypoal-
lergenic) lead to increased exposure. For non-breastfed
highly exposed children, the calculation shown in Table9
also includes an additional contribution from FCM made
of uncoated aluminium. If such additional contributions
are strictly reduced or avoided, the JECFA-derived PTWI
is not or only slightly exceeded. However, an (partly sig-
nificant) exceedance of the EFSA-derived TWI is possible
particularly for high-intake consumers and children fed
with certain adapted foods. This population group is thus
subject to a potentially increased health risk which has to
be seen critically, especially with regard to developmental
neurotoxicity.
Table 8 Total weekly aluminium exposure for children (> 36months) and adults, calculated as oral exposure equivalents
Bold indicates the sum of the exposure estimation which is used for the risk assessment later on
Exposure-contribution Weekly aluminium exposure in mg Al/kg bw/week
Children 3–10years,
data from ANSES
(2011)
Children 11–14years,
data from ANSES
(2011)
Adults > 14years
data from this
work
(1) Food, average consumers 0.49–0.64 0.34 0.18–0.21
(2) Toothpaste, mean Al-content (not abrasive) 0.005 0.005 0.003
(3) Lipsticks – 0.042–0.27 0.029–0.19
(4) Sunscreens 0.02–0.24 0.02–0.21 0.02–0.16
(5) Antiperspirants – 0.98–2.04 0.69–1.43
Sum normally exposed persons (sum (1) − (5)) 0.5–0.9 1.4–2.9 0.9–2.0
Sum normally exposed persons without antiperspirants (sum (1) − (4)) 0.5–0.9 0.4–0.8 0.2–0.6
(6) Food, high-intake consumers 0.82–1.02 0.58 0.42–0.44
(7) Abrasive toothpaste, high Al-content – 1.0 0.72
(8) FCM (containing aluminium) 0.50 0.50 0.50
Sum highly exposed persons (sum (2) − (5) + Sum (6) − (8)) 1.3–1.8 3.1–4.6 2.4–3.4
Sum highly exposed persons without antiperspirants, abrasive toothpaste
and FCM (sum (2) − (4) + (6))
0.8–1.3 0.6–1.1 0.5–0.8
Other contributions
Antacids, containing aluminium – – 1.85–2.88mg/kg
bw per applica-
tion
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3516 Archives of Toxicology (2019) 93:3503–3521
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Risk assessment forchildren andadolescents
For children between 3 and 10years of age, summed alu-
minium exposure (Table9) from the contributions consid-
ered here exceeds the EFSA-derived TWI only in the highly
exposed group (details see Table8). The JECFA-derived
PTWI is not exceeded. For normally exposed children in
this age group, weekly aluminium intake does not exceed the
EFSA-derived TWI. An increased health risk is, therefore,
unlikely.
A different picture emerges for 11 to 14 years old. For this
population group, additional contributions from cosmetic
articles have to be considered. The use of aluminium-con-
taining antiperspirants and abrasive toothpaste with a high
aluminium content results in a total aluminium exposure in
the highly exposed group that is almost fivefold as high as
the EFSA-derived TWI (or 2.5-fold as high as the JECFA-
derived PTWI). An increased health risk is possible on the
basis of these values. Since aluminium also accumulates in
the body and remains there for a very long time even after
a reduction in intake, a high exposure of very young people
must be viewed particularly critically.
However, if aluminium-containing antiperspirants,
abrasive toothpaste and FCM made of uncoated alumin-
ium are avoided, the weekly intake is reduced to a range
of 0.4–0.8mg Al/kg bw/week for normally exposed indi-
viduals and 0.6–1.1mg Al/kg bw/week for highly exposed
individuals (see Table8). The JECFA-derived PTWI would
thus not be exceeded and the EFSA-derived TWI would
only be slightly exceeded in the high exposure group. An
increased health risk would, therefore, be unlikely if the
above-mentioned avoidable contributions were omitted
consequently.
Risk assessment foradults
Similar to adolescents, the aluminium exposure for adults
may, in some cases significantly, exceed the EFSA-derived
TWI for normally exposed adults. In the highly exposed
group, even the JECFA-derived PTWI may be exceeded by
more than 50% (Table9) and, thus, an increased health risk
is possible. Cosmetic products contribute to a large (and
through avoidance controllable) extent to this overall expo-
sure (details see Table8). Aluminium can cross the placen-
tal barrier, and the unborn child could also be exposed to
aluminium. Antacids that contain bioavailable aluminium
or form it in reaction with gastric acid can be an additional
contribution to the overall aluminium exposure shown in
Table9. Meanwhile, the WHO has removed these antacids
from its “Model List of Essential Medicines” (WHO 2017).
By consequent reduction or avoidance of additional con-
tributions (e.g. cosmetics, FCM), the overall aluminium
intake would be significantly lower than both the JECFA-
derived PTWI and the EFSA-derived TWI. Hence, an
increased health risk would be unlikely.
Uncertainty analysis
Uncertainties inthetoxicological data
There isno consensus regarding the derivation of a (P)TWI
(see above). Depending on the (P)TWI used for comparison
Table 9 Summary of the aggregated exposure values (as oral expo-
sure equivalents) for the different population groups and comparison
with the oral tolerable weekly intake of 1mg Al/kg bw/week (EFSA
2008) and 2mg Al/kg bw/week (JECFA 2012); values printed in bold
type refer to exhaustion or excess of the respective (P)TWI; “normal
exposure” refers to average consumers and does not take into account
additional (avoidable) inputs (e.g. antiperspirants, food contact
materials), which were included in “high exposure” calculation (for
details, see Tables7, 8)
Population/age group Weekly aluminium
exposure in mg Al/kg
bw/week
Percentage of the EFSA-
TWI of 1mg/kgKG/
week
Percentage of the JECFA-
PTWI of 2mg/kgKG/week
Infants, breastfed 1.1–2.3 110–230 55–115
Infants and toddlers (1–6months), fed with infant formula,
normal exposure
1.2–2.6 120–260 60–130
Infants and toddlers (1–6months), fed with infant formula,
high exposure
2.0–3.3 200–330 100–165
Infants and toddlers (7months–3years), normal exposure 1.4–2.7 140–270 70–135
Infants and toddlers (7months–3years), high exposure 2.1–3.4 210–340 105–170
Children (3–10years), normal exposure 0.5–0.9 50–90 25–45
Children (3–10years), high exposure 1.3–1.8 130–180 65–90
Adolescents (11–14years), normal exposure 1.4–2.9 140–290 70–145
Adolescents (11–14years), high exposure 3.1–4.6 310–460 155–230
Adults (> 14years), normal exposure 0.9–2.0 90–200 45–100
Adults (> 14years), high exposure 2.4–3.4 240–340 120–170
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3517Archives of Toxicology (2019) 93:3503–3521
1 3
with the calculated exposure, different conclusions concern-
ing a potential health risk may arise, because a particular
exposure might at the same time exhaust or exceed the
EFSA-derived TWI, but not the JECFA-derived PTWI.
Further research is needed concerning relevant toxico-
logical endpoints, such as carcinogenicity and neurotoxicity
of aluminium compounds. Nevertheless, up to now, there
is no causal relationship between aluminium exposure and
Alzheimer’s disease or breast cancer development.
Uncertainties inthedata used forexposure assessment
Aggregated exposure assessment based on several data
sources as presented here naturally suffers from inherent
uncertainties due to the different quality of the underlying
data. Whereas the data on food exposure are based on com-
paratively large consumption and content data at individual
level, the measured aluminium contents and data of use of
cosmetics are based on assumptions or data sources that
are not necessarily representative or do not cover the full
variability. Thus, the contribution of each source to the total
exposure might be affected by those uncertainties.
The dietary exposure assessment for adults is based on
data from a pilot TDS. In consequence of the pilot char-
acter, uncertainties due to limited stratification regarding
regional and seasonal variations in eating habits and the
limited access to market share data arise. Nevertheless, the
impact on the exposure outcome is considered as minor,
since regional and seasonal variance is assumed to be low
for environmental contaminants such as aluminium. In addi-
tion, standardised sampling strategies were applied to mini-
mise the effect of missing market share data. Probably the
highest amount of uncertainty, however, arises from a pos-
sible change of the consumption habits of consumers since
2005/2006, when the consumption data collection period of
the NVS II took place. For infants and children, more recent
data from the French TDSs were used. Nevertheless, uncer-
tainties may arise from different dietary behaviour of Ger-
man infants and children, despite the similar culture space.
A TDS measures mean analyte contents of pooled sam-
ples. Hence, it is appropriate to estimate background expo-
sure levels. High analyte contents of particular single foods
cannot be detected. Therefore, individuals, who frequently
consume certain highly contaminated products, such as
brand loyal consumers, might be exposed to a much higher
extent.
The considered data on aluminium release from FCM are
limited to a small selection of products. A certain overes-
timation of the respective contribution to aluminium expo-
sure might be possible, because the data are obtained under
conservative conditions (food simulant, time, temperature).
However, since this contribution was considered only for
highly exposed individuals, the impact on the total intake
should be small. The data on aluminium contents of cos-
metic products are very limited, too. Both the extent and
the direction (under- vs. overestimation) of the contribution
to the total aluminium exposure are uncertain. The standard
application amounts and frequencies for different cosmetic
products according to SCCS (2018) are suitable for a con-
servative risk assessment (application of 90th percentile,
each). Nevertheless, different application habits may occur.
For example, recent data (Manová etal. 2013) indicate that
the number of days on which sunscreen is used may be sig-
nificantly higher than assumed here and that there is a vari-
ability in gender and age that is not sufficiently reflected by
the standards used here.
Due to the lack of representative quantitative data on alu-
minium contents in toys, the contribution from this source is
not considered in the assessment presented here.
Methodological uncertainties
Since for aluminium, systemic toxicity has been extensively
studied only after oral intake, contributions from dermal
exposure were converted into a systemic exposure based
on the dermal absorption rate of 0.014%, and afterwards
recalculated into oral exposure equivalents that would result
in the same systemic exposure, applying the oral absorp-
tion rate of 0.1%. The dermal absorption rate is based on
an invivo study on antiperspirants (Flarend etal. 2001).
For products other than antiperspirants leading to dermal
aluminium exposure (e.g. sunscreen), it is unknown to what
extent the use of the absorption rate of 0.014% can be justi-
fied, because these products usually contain matrix com-
ponents or aluminium compounds different from those in
antiperspirants (e.g. aluminium oxide or hydroxide instead
of ACH, as often used in antiperspirants) and are applied
to other areas of the skin. In addition, dermal absorption
rates observed in a recent invitro study are many times
higher (between 0.6 and 2.0%) and suggest that aluminium
is absorbed much better through damaged skin than through
intact skin (Pineau etal. 2012). However, due to the some-
what artificial application mode as well as some uncertain-
ties in the invitro study, and in the absence of other data, the
absorption rate of 0.014% from the invivo study was used to
calculate the systemic exposure after dermal absorption for
all cosmetic products included here. However, it should be
considered that higher aluminium levels might result from
the use of aluminium-containing antiperspirants on damaged
skin (e.g. after sunburn, shaving). Uncertainties may arise
from the application of the oral absorption rate of 0.1%, too,
because this value only represents an average of the results
reported in a large number of studies with highly differing
absorption rates (see above). For example, the oral bioavail-
ability of aluminium ingested via lipstick might be very low
due to the use of insoluble colour pigments and it is not
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3518 Archives of Toxicology (2019) 93:3503–3521
1 3
known whether the aluminium oxide or hydroxide used as
an abrasive in toothpaste is bioavailable to the same extent
as aluminium compounds ingested with food.
The aggregated analysis of the different exposure contri-
butions carried out here allows the comparison of the sig-
nificance of the individual pathways and the provision of
options for risk management. However, data on correlations
between different exposure contributions are missing. There-
fore, uncertainties arise from the aggregated consideration
of different contributions. A probabilistic assessment might
be more appropriate, but would require sound assumptions
on correlations or data on consumer behaviour considering
all exposure contributions based on the same study popula-
tion. With this, evaluation of variability and a more accurate
exposure assessment on high percentiles would be possible.
Additionally, human biomonitoring data could provide a
valid basis for the actual internal exposure resulting from
aggregated external exposure. The 95th percentile of the uri-
nary aluminium concentration of not occupationally exposed
adults, estimated by the MAK Commission (Klotz etal.
2019), corresponds to an oral exposure equivalent, which is
in good accordance with exposure estimation presented here.
However, these data are less appropriate to derive specific
risk management measures.
Conclusions
More recent data (see results) indicate a significant reduc-
tion in aluminium intake from food compared to older data
resulting in only a slight exceedance of the weekly tolerable
aluminium intake (TWI) of 1mgAl/kgbw/week derived by
the EFSA (2008) for high-intake consumers aged 3–6years.
For all other age groups, even high food consumption does
not result in an exceedance of the TWI. The highest average
exposure (3–6years old children) is 64% of the TWI. Hence,
no health risk due to dietary uptake alone is to be expected.
However, additional sources of exposure, such as the
use of FCM made of uncoated aluminium, or the frequent
use of aluminium-containing cosmetic products, could
result in a permanent exceedance of the (P)TWI for a very
large number of consumers in all age groups and lead to
increased accumulation of aluminium in the body. A short-
term exceedance of a (P)TWI does not automatically result
in a health risk. Nevertheless, considering regular long-
term intake levels for aluminium of multiples of the (P)
TWI (Table9), the existing contributions should be criti-
cally reviewed to reduce the overall aluminium exposure.
This holds true even more if the severity of possible adverse
effects (neurological damage, kidney and urinary tract dam-
age) and the long half-life of aluminium in the human body
are also taken into account. In this course, it seems suitable
to
• exclusively breastfeed infants in the first 6months, if
possible
• examine the sources of contamination of foodstuffs with
aluminium during production, processing and packaging
(e.g. the elimination of aluminium baking trays in the
production of lye biscuits (BfR 2002), the avoidance of
uncoated aluminium meal trays to heat food or keep it
warm (BfR 2017b)) and, where possible and appropriate,
the use of raw materials with low aluminium content
• avoid contact of uncoated aluminium FCM with (espe-
cially) acidic and salty foodstuffs
• reduce usage of aluminium-containing cosmetics such as
antiperspirants or abrasive toothpaste
Compliance with ethical standards
Conflict of interest The authors declare that they do not have potential
conflicts of interest.
Open Access This article is distributed under the terms of the Crea-
tive Commons Attribution 4.0 International License (http://creat iveco
mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribu-
tion, and reproduction in any medium, provided you give appropriate
credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
References
AGES (2017) Aluminium in Lebensmitteln und anderen verbrauch-
ernahen Produkten 2010–2017. Österreichische Agentur für
Gesundheit und Ernährungssicherheit GmbH, Wien, Österreich.
https ://www.ages.at/wisse n-aktue ll/publi katio nen/alumi nium-in-
leben smitt eln-und-ander en-verbr auche rnahe n-produ kten-2010-
2017/. Accessed 24 Oct 2019
ANSES (2011) Second French total diet study (TDS 2)—report 1,
inorganic contaminants, minerals, persistent organic pollutants,
mycotoxins and phytoestrogens. French agency for food, envi-
ronmental and occupational health and safety. https ://www.anses
.fr/en/syste m/files /PASER 2006s a0361 Ra1EN .pdf. Accessed 19
June 2019
ANSES (2016) Infant Total Diet Study (iTDS)—Tome 2—Partie 2,
Composés inorganiques. French Agency for Food, Environmental
and Occupational Health & Safety. https ://www.anses .fr/en/conte
nt/infan t-total -diet-study -itds. Accessed 19 June 2019
Arnich N, Sirot V, Rivière G etal (2012) Dietary exposure to trace
elements and health risk assessment in the 2nd French Total
Diet Study. Food Chem Toxicol 50(7):2432–2449. https ://doi.
org/10.1016/j.fct.2012.04.016
Beldì G, Jakubowska N, Peltzer MA, Simoneau C (2016) Testing
approaches for the release of metals from ceramic articles - in
support of the revision of the Ceramic Directive 84/500/EEC,
EUR 28363 EN. https ://doi.org/10.2788/40268 3
BfR (2002) Erhöhte Gehalte von Aluminium in Laugengebäck—Stel-
lungnahme des BfR vom 25. November 2002. https ://www.bfr.
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

3519Archives of Toxicology (2019) 93:3503–3521
1 3
bund.de/cm/343/erhoe hte_gehal te_von_alumi nium_in_lauge
ngeba eck.pdf. Accessed 19 June 2019
BfR (2007) Keine Alzheimer-Gefahr durch Aluminium aus Bedarf-
sgegenständen—Aktualisierte gesundheitliche Bewertung Nr.
033/2007 des BfR vom 22. Juli 2007. https ://www.bfr.bund.de/
cm/343/keine _alzhe imer_gefah r_durch _alumi nium_aus_bedar
fsgeg ensta enden .pdf. Accessed 19 June 2019
BfR (2008) Aluminium in Apfelsaft: Lagerung von Fruchtsäften nicht
in Aluminiumtanks—Gesundheitliche Bewertung Nr. 034/2008
des BfR vom 18. Juni 2008. https ://www.bfr.bund.de/cm/343/
alumi nium_in_apfel saft_lager ung_von_fruch tsaef ten_nicht
_in_alumi niumt anks.pdf. Accessed 19 June 2019
BfR (2012) Aluminiumgehalte in Säuglingsanfangs- und Folgenah-
rung—Aktualisierte Stellungnahme Nr. 012/2012 des BfR vom
20. April 2012. https ://www.bfr.bund.de/cm/343/alumi niumg
ehalt e-in-saeug lings anfan gs-und-folge nahru ng.pdf. Accessed
19 June 2019
BfR (2014) Aluminiumhaltige Antitranspirantien tragen zur Aufnahme
von Aluminium bei—Stellungnahme Nr. 007/2014 des BfR vom
26. Februar 2014. http://www.bfr.bund.de/cm/343/alumi niumh
altig e-antit ransp irant ien-trage n-zur-aufna hme-von-alumi nium-
bei.pdf. Accessed 19 June 2019
BfR (2017a) State of play on the subject of aluminium in cocoa and
chocolate (unpublished data)
BfR (2017b) Unbeschichtete Aluminium-Menüschalen: Erste
Forschungsergebnisse zeigen hohe Freisetzung von Aluminiu-
mionen—Stellungnahme Nr. 007/2017 des BfR vom 29. Mai
2017. https ://www.bfr.bund.de/cm/343/unbes chich tete-alumi
nium-menue schal en-erste -forsc hungs ergeb nisse -zeige n-hohe-
freis etzun g-von-alumi niumi onen.pdf. Accessed 19 June 2019
Biego GH, Joyeux M, Hartemann P, Debry G (1998) Determination
of mineral contents in different kinds of milk and estimation of
dietary intake in infants. Food Addit Contam 15(7):775–781.
https ://doi.org/10.1080/02652 03980 93747 09
BVL (2019) BVL-Report 13.4 Berichte zur Lebensmittelsicherheit.
Monitoring 2017. Bundesamt für Verbraucherschutz und Leb-
ensmittelsicherheit. https ://www.bvl.bund.de/Share dDocs /Downl
oads/01_Leben smitt el/01_lm_mon_dokum ente/01_Monit oring
_Beric hte/archi v/lmm_beric ht_2017.pdf?__blob=publi catio
nFile &v=6. Accessed 19 June 2019
Candy JM, McArthur FK, Oakley AE etal (1992) Aluminium accu-
mulation in relation to senile plaque and neurofibrillary tangle
formation in the brains of patients with renal failure. J Neurol Sci
107(2):210–218. https ://doi.org/10.1016/0022-510X(92)90291 -R
CFS (2013) The First Hong Kong Total Diet Study Report No. 5. Cen-
tre for Food Safety, Food and Environmental Hygiene Depart-
ment, The Government of the Hong Kong Special Administra-
tive Region. https ://www.cfs.gov.hk/engli sh/progr amme/progr
amme_firm/files /Repor t_on_1st_HKTDS _Metal lic_Conta minan
ts.pdf. Accessed 19 June 2019
Chao HH, Guo CH, Huang CB etal (2014) Arsenic, cadmium, lead,
and aluminium concentrations in human milk at early stages
of lactation. Pediatr Neonatol 55(2):127–134. https ://doi.
org/10.1016/j.pedne o.2013.08.005
Chuchu N, Patel B, Sebastian B, Exley C (2013) The aluminium con-
tent of infant formulas remains too high. BMC Pediatr 13:162.
https ://doi.org/10.1186/1471-2431-13-162
COT (2013) Statement on the potential risks from aluminium in the
infant diet. Committee on toxicity of chemicals in food, con-
sumer products and the environment (COT). https ://cot.food.
gov.uk/sites /defau lt/files /cot/state alumi nium.pdf. Accessed 19
June 2019
Dabeka R, Fouquet A, Belisle S, Turcotte S (2011) Lead, cadmium and
aluminum in Canadian infant formulae, oral electrolytes and glu-
cose solutions. Food Addit Contam Part A Chem Anal Control
Expo Risk Assess 28(6):744–753. https ://doi.org/10.1080/19393
210.2011.57179 5
Darbre PD (2001) Underarm cosmetics are a cause of breast cancer.
Eur J Cancer Prev 10(5):389–393
de Ligt R, van Duijn E, Grossouw D etal (2018) Assessment of der-
mal absorption of aluminum from a representative antiperspirant
formulation using a 26Al microtracer approach. Clin Transl Sci.
https ://doi.org/10.1111/cts.12579
Dofkova M, Nurmi T, Berg K etal (2016) Development of harmo-
nised food and sample lists for total diet studies in five Euro-
pean countries. Food Addit Contam A Chem Anal Control Expo
Risk Assess 33(6):933–944. https ://doi.org/10.1080/19440
049.2016.11897 70
EDQM (2013) Metals and alloys used in food contact materials and
articles. Council of Europe, European Directorate for Quality of
Medicines & Healthcare, Strasbourg, France. https ://www .edqm.
eu/en/food-conta ct-mater ials. Accessed 24 Oct 2019
EFSA (2008) Safety of aluminium from dietary intake—scientific opin-
ion of the panel on food additives, flavourings, processing aids
and food contact materials (AFC). EFSA J 6(7):754. https ://doi.
org/10.2903/j.efsa.2008.754
EFSA (2011) The food classification and description system FoodEx
2 (draft-revision 1). EFSA Supporting Publications 8(12), 215E.
https ://doi.org/10.2903/sp.efsa.2011.EN-215
EFSA (2012) Guidance on selected default values to be used by the
EFSA Scientific Committee, scientific panels and units in the
absence of actual measured data. EFSA J 10(3):2579. https ://doi.
org/10.2903/j.efsa.2012.2579
EFSA (2018) Re-evaluation of aluminium sulphates (E 520–523) and
sodium aluminium phosphate (E 541) as food additives. EFSA J
16(7):e05372. https ://doi.org/10.2903/j.efsa.2018.5372
EFSA/FAO/WHO (2011) Towards a harmonised total diet study
approach: a guidance document. In: EFSA Working Group on
Total Diet Studies (ed). http://www.who.int/foods afety /publi catio
ns/tds_guida nce/en/. Accessed 12 Sept 2019
Ertl K, Goessler W (2018) Aluminium in foodstuff and the influence
of aluminium foil used for food preparation or short time stor-
age. Food Addit Contam Part B 11(2):153–159. https ://doi.
org/10.1080/19393 210.2018.14428 81
Exley C, Charles LM, Barr L, Martin C, Polwart A, Darbre PD
(2007) Aluminium in human breast tissue. J Inorg Bio-
chem 101(9):1344–1346. https ://doi.org/10.1016/j.jinor
gbio.2007.06.005
Fakri S, Al-Azzawi A, Al-Tawil N (2006) Antiperspirant use as
a risk factor for breast cancer in Iraq. East Mediterr Health J
12(3–4):478–482
Fernandez-Lorenzo JR, Cocho JA, Rey-Goldar ML, Couce M, Fraga
JM (1999) Aluminum contents of human milk, cow’s milk, and
infant formulas. J Pediatr Gastroenterol Nutr 28(3):270–275
Filippini T, Tancredi S, Malagoli C etal (2019) Aluminum and tin:
food contamination and dietary intake in an Italian population.
J Trace Elem Med Biol 52:293–301. https ://doi.org/10.1016/j.
jtemb .2019.01.012
Finkelstein P, Wulf RJ (1974) The uptake, distribution, and excretion of
a commercial aerosol antiperspirant by the monkey. J Soc Cosmet
Chem 25(12):645–654
Fischer L (2014) Wie gefährlich ist Aluminium? In: Spektrum.de. https
://www.spekt rum.de/wisse n/wie-gefae hrlic h-ist-alumi nium-5-
fakte n/13008 12. Accessed 19 June 2019 (14.07.2014)
Flarend R, Bin T, Elmore D, Hem SL (2001) A preliminary study of
the dermal absorption of aluminium from antiperspirants using
aluminium-26. Food Chem Toxicol 39(2):163–168. https ://doi.
org/10.1016/S0278 -6915(00)00118 -6
FSANZ (2011) The 23rd Australian Total Diet Study. Food Standards
Australia New Zealand. http://www.foods tanda rds.gov.au/publi
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

3520 Archives of Toxicology (2019) 93:3503–3521
1 3
catio ns/Pages /23rda ustra liant otald 5367.aspx. Accessed 19 June
2019
FSANZ (2014) The 24th Australian Total Diet Study. Food Stand-
ards Australia New Zealand. http://www.foods tanda rds.gov.au/
publi catio ns/Docum ents/1778-FSANZ _AustD ietSt udy-web.pdf.
Accessed 19 June 2019
Golub MS, Germann SL (2001) Long-term consequences of develop-
mental exposure to aluminum in a suboptimal diet for growth
and behavior of Swiss Webster mice. Neurotoxicol Teratol
23(4):365–372. https ://doi.org/10.1016/S0892 -0362(01)00144 -1
Hunnius C (2014) Pharmazeutisches Wörterbuch, 11. Auflage vom
15. August 2014, 11th edn. De Gruyter, Berlin
IAI (2018) Primary aluminium production in 2018, world alumin-
ium—the website of the International Aluminium Institute. In:
http://www.w or ld -alumi nium.org/stati stics /#map. Accessed 19
June 2019
IKW (2016a) Group data sheet No 73: Antiperspirant aerosol
spray (with antiperspirant salt). In: http://gmb.ikw.org/index
_en.php?p=mb&id=159&actio n=selec tMerk blatt . Accessed
19 June 2019
IKW (2016b) Group data sheet No 79: Antiperspirant creme. In:
http://gmb.ikw.org/index _en.php?p=mb&id=159&actio
n=selec tMerk blatt . Accessed 19 June 2019
IKW (2016c) Group data sheet No 128: Antiperspirant liquid squeeze
pack or pump spray (with antiperspirant salt). In: http://gmb.
ikw.org/index _en.php?p=mb&id=159&actio n=selec tMerk
blatt . Accessed 19 June 2019
IKW (2016d) Group data sheet No 129: Antiperspirant roll-
on (with antiperspirant salt). In: http://gmb.ikw.org/index
_en.php?p=mb&id=159&actio n=selec tMerk blatt . Accessed
19 June 2019
Inan-Eroglu E, Ayaz A (2018) Is aluminum exposure a risk factor
for neurological disorders? J Res Med Sci 23:51. https ://doi.
org/10.4103/jrms.JRMS_921_17
Inker LA, Levey AS (2014) 3—assessment of glomerular filtration
rate in acute and chronic settings. In: Gilbert SJ, Weiner DE
(eds) National Kidney Foundation Primer on Kidney Diseases,
6th edn. W.B. Saunders, Philadelphia, pp 26–32
Ionescu JG, Novotny J, Stejskal V, Lätsch A, Blaurock-Busch E,
Eisenmann-Klein M (2007) Breast tumours strongly accumu-
late transition metals. Maedica J Clin Med 2(1):5–11
IPCS (1997) Environmental Health Criteria 194—Aluminium. Inter-
national Programme on Chemical Safety. http://www.inche
m.org/docum ents/ehc/ehc/ehc19 4.htm. Accessed 19 June 2019
JECFA (2007) Safety evaluation of certain food additives and con-
taminants Prepared by the Sixty-seventh meeting of the Joint
FAO/WHO Expert Committee on Food Additives (JECFA),
CH, series 58. World Health Organization, Geneva
JECFA (2012) Safety evaluation of certain food additives and con-
taminants prepared by the Seventy-fourth meeting of the Joint
FAO/WHO Expert Committee on Food Additives, CH, series
65. World Health Organization, Geneva
Klein GL (2019) Aluminum toxicity to bone: a multisystem effect?
Osteoporos Sarcopenia 5(1):2–5. https ://doi.org/10.1016/j.
afos.2019.01.001
Klotz K, Meyer-Baron M, van Thriel C etal (2018) Addendum
zu Aluminium [BAT Value Documentation in German lan-
guage, 2018]. MAK Collect Occup Health Saf. https ://doi.
org/10.1002/35276 00418 .bb742 990ve rd002 3
Klotz K, Drexler H, Hartwig A, Commission MAK (2019) Adden-
dum zu Aluminium [BAT Value Documentation in German
language, 2019]. MAK Collect Occup Health Saf. https ://doi.
org/10.1002/35276 00418 .bb742 990ve rd002 4
Kolbaum AE, Berg K, Müller F, Kappenstein O, Lindtner O (2019)
Dietary exposure to elements from the German Pilot Total
Diet Study (TDS). Food Addit Contam Part A. https ://doi.
org/10.1080/19440 049.2019.16689 67
Krachler M, Prohaska T, Koellensperger G, Rossipal E, Stingeder
G (2000) Concentrations of selected trace elements in human
milk and in infant formulas determined by magnetic sector field
inductively coupled plasma-mass spectrometry. Biol Trace
Elem Res 76(2):97–112. https ://doi.org/10.1385/bter:76:2:97
Krems C, Bauch A, Götz A etal (2006) Methoden der Nationalen
Verzehrsstudie II. Ernähr Umschau 53(2):44–50
Krewski D, Yokel RA, Nieboer E etal (2007) Human health risk
assessment for aluminium, aluminium oxide, and aluminium
hydroxide. J Toxicol Environ Health Part B 10(sup1):1–269.
https ://doi.org/10.1080/10937 40070 15977 66
LAVES (2017) Tätigkeitsbericht 2016. Niedersächsisches Landesamt
für Verbraucherschutz und Lebensmittelsicherheit (LAVES),
Oldenburg, Germany, p 93. https ://www.laves .niede rsach sen.de/
servi ce/publi katio nen/jahre sberi chte_verbr auche rschu tzber ichte
/taeti gkeit sberi cht-2016-15688 8.html. Accessed 24 Oct 2019
Lenhart CM, Wiemken A, Hanlon A, Perkett M, Patterson F (2017)
Perceived neighborhood safety related to physical activity but
not recreational screen-based sedentary behavior in adolescents.
BMC Public Health. https ://doi.org/10.1186/s1288 9-017-4756-z
LGL (2018) LGL Jahresbericht 2017. Bayerisches Landesamt für
Gesundheit und Lebensmittelsicherheit. https ://www.lgl.bayer
n.de/publi katio nen/doc/lgl_jahre sberi cht_2017.pdf. Accessed
19 June 2019
Liang J, Liang X, Cao P etal (2019) A preliminary investigation of
naturally occurring aluminum in grains, vegetables, and fruits
from some areas of China and dietary intake assessment. J Food
Sci 84(3):701–710. https ://doi.org/10.1111/1750-3841.14459
Liu S, Hammond SK, Rojas-Cheatham A (2013) Concentrations and
potential health risks of metals in lip products. Environ Health
Perspect 121:705–710. https ://doi.org/10.1289/ehp.12055 18
Lubecki M (2014) Daily dose of aluminium—a health risk? Absorption
via food, cosmetics and other consumer products. In: Chemisches
und Veterinäruntersuchungsamt Stuttgart/Baden-Württemberg.
http://www.cvuas .de/pub/beitr ag.asp?subid =1&Thema _ID=3&
ID=2012&lang=EN&Pdf=No. Accessed 19 June 2019
Lukiw WJ, Kruck TPA, Percy ME etal (2019) Aluminum in neurologi-
cal disease—a 36year multicenter study. J Alzheimers Dis Par-
kinsonism 8(6):457. https ://doi.org/10.4172/2161-0460.10004 57
Mannello F, Tonti GA, Medda V, Simone P, Darbre PD (2011) Analysis
of aluminium content and iron homeostasis in nipple aspirate
fluids from healthy women and breast cancer-affected patients.
J Appl Toxicol 31(3):262–269. https ://doi.org/10.1002/jat.1641
Manová E, von Goetz N, Keller C, Siegrist M, Hungerbühler K (2013)
Use patterns of leave-on personal care products among Swiss-
German children, adolescents, and adults. Int J Environ Res
Public Health 10(7):2778–2798. https ://doi.org/10.3390/ijerp
h1007 2778
Martinez CS, Vera G, Ocio JAU etal (2018) Aluminum exposure for
60days at an equivalent human dietary level promotes peripheral
dysfunction in rats. J Inorg Biochem 181:169–176. https ://doi.
org/10.1016/j.jinor gbio.2017.08.011
Mehpara Farhat S, Mahboob A, Ahmed T (2019) Oral exposure to
aluminum leads to reduced nicotinic acetylcholine receptor gene
expression, severe neurodegeneration and impaired hippocam-
pus dependent learning in mice. Drug Chem Toxicol. https ://doi.
org/10.1080/01480 545.2019.15874 52
Mirick DK, Davis S, Thomas DB (2002) Antiperspirant use and the
risk of breast cancer. JNCI J Natl Cancer Inst 94(20):1578–1580.
https ://doi.org/10.1093/jnci/94.20.1578
Mold M, Cottle J, King A, Exley C (2019) Intracellular aluminium
in inflammatory and glial cells in cerebral amyloid angiopa-
thy: a case report. Int J Environ Res Public Health. https ://doi.
org/10.3390/ijerp h1608 1459
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

3521Archives of Toxicology (2019) 93:3503–3521
1 3
MPI (2016) 2016 New Zealand Total Diet Study. Ministry for Primary
Industries of New Zealand. https ://www.mpi.govt.nz/food-safet
y/food-monit oring -and-surve illan ce/new-zeala nd-total -diet-study
/. Accessed 12 Sept 2019
MRI (2008) Nationale Verzehrsstudie II—Die bundesweite Befragung
zur Ernährung von Jugendlichen und Erwachsenen. Ergebnisber-
icht, Teil 2. Max Rubner-Institut—Bundesforschungsinstitut für
Ernährung und Lebensmittel, Karlsruhe DE. https ://www.bmel.
de/Share dDocs /Downl oads/Ernae hrung /NVS_Ergeb nisbe richt
Teil2 .pdf. Accessed 12 Sept 2019
Namer M, Luporsi E, Gligorov J, Lokiec F, Spielmann M (2008) The
use of deodorants/antiperspirants does not constitute a risk fac-
tor for breast cancer. Bull Cancer 95(9):871–880. https ://doi.
org/10.1684/bdc.2008.0679
Nicholson S, Exley C (2007) Aluminum: a potential pro-oxidant in
sunscreens/sunblocks? Free Radic Biol Med 43(8):1216–1217.
https ://doi.org/10.1016/j.freer adbio med.2007.07.010
Nie J (2018) Exposure to aluminum in daily life and Alzheimer’s
disease. In: Niu Q (ed) Neurotoxicity of aluminum advances in
experimental medicine and biology, vol 1091. Springer, Singa-
pore. https ://doi.org/10.1007/978-981-13-1370-7_6
NILU (2011) Metaller i næringsmidler, kroppspleieprodukter og kos-
metikk. Bestemmelse av aluminium, kadmium og barium. Opp-
dragsrapport. (NILU OR 16/2011). Norwegian Institute for Air
Research. ISBN: 978-82-425-2377-8
Ogoshi K, Yanagi S, Moriyama T, Arachi H (1994) Accumulation
of aluminum in cancers of the liver, stomach, duodenum and
mammary glands of rats. J Trace Elem Electrolytes Health Dis
8(1):27–31
Oneda S, Takasaki T, Kuriwaki K etal (1994) Chronic toxicity and
tumorigenicity study of aluminum potassium sulfate in B6C3F1
mice. InVivo 8(3):271–278
PEI (2015) Sicherheitsbewertung von Aluminium in Impfstoffen.
Bulletin zur Arzneimittelsicherheit Informationen aus BfArM
und PEI (3):7. https ://www.pei.de/Share dDocs /Downl oads/vigil
anz/bulle tin-zur-arzne imitt elsic herhe it/2015/3-2015.pdf?__
blob=publi catio nFile &v=10. Accessed 19 June 2019
Pi X, Jin L, Li Z etal (2019) Association between concentrations of
barium and aluminum in placental tissues and risk for orofacial
clefts. Sci Total Environ 652:406–412. https ://doi.org/10.1016/j.
scito tenv.2018.10.262
Pineau A, Guillard O, Fauconneau B etal (2012) Invitro study of
percutaneous absorption of aluminum from antiperspirants
through human skin in the Franz™ diffusion cell. J Inorg Bio-
chem 110:21–26. https ://doi.org/10.1016/j.jinor gbio.2012.02.013
Poirier J, Semple H, Davies J etal (2011) Double-blind, vehicle-
controlled randomized twelve-month neurodevelopmental
toxicity study of common aluminum salts in the rat. Neuro-
science 193:338–362. https ://doi.org/10.1016/j.neuro scien
ce.2011.05.008
Priest N, Newton D, Day J, Talbot R, Warner A (1995) Human metabo-
lism of aluminium-26 and gallium-67 injected as citrates. Hum
Exp Toxicol 14(3):287–293. https ://doi.org/10.1177/09603 27195
01400 309
RIVM (2006) Cosmetics Fact Sheet to assess the risks for the
consumer, Updated version for ConsExpo 4, RIVM report
320104001/2006. Rijksinstituut voor Volksgezondheid en
Milieu. https ://www.rivm.nl/bibli othee k/rappo rten/32010 4001.
pdf. Accessed 24 Oct 2019
RKI (2016) The 20 most frequent objections to vaccinations—and
responses by immunisation experts of the Robert Koch Institute
and the Paul-Ehrlich-Institut. In: https ://www.rki.de/EN/Conte
nt/Insti tute/Depar tment sUnit s/InfDi sease Epide m/Div33 /Objec
tions _and_Respo nses.html. Accessed 19 June 2019
RKI (2017) Vaccination schedule In: Robert Koch-Institut. https ://
www.rki.de/DE/Conte nt/Infek t/Impfe n/Mater ialie n/Downl
oads-Impfk alend er/Impfk alend er_Engli sch.pdf?__blob=publi
catio nFile . Accessed 19 June 2019
Rodriguez J, Mandalunis PM (2018) A review of metal exposure and
its effects on bone health. J Toxicol 2018:4854152. https ://doi.
org/10.1155/2018/48541 52
Romaniuk A, Lyndin M, Sikora V, Lyndina Y, Romaniuk S, Sikora K
(2017) Heavy metals effect on breast cancer progression. J Occup
Med Toxicol (London, England) 12:32. https ://doi.org/10.1186/
s1299 5-017-0178-1
Romanowicz-Makowska H, Forma E, Bryś M, Krajewska WM, Smo-
larz B (2012) Concentration of cadmium, nickel and aluminium
in female breast cancer. Pol J Pathol 62(4):257–261
RoteListe (2018) Rote Liste—Arzneimittelinformationen für
Deutschland In. https ://onlin e.rote-liste .de/. Accessed 19 June
2019
Sander S, Kappenstein O, Ebner I etal (2018) Release of aluminium
and thallium ions from uncoated food contact materials made
of aluminium alloys into food and food simulant. PLoS One
13(7):e0200778. https ://doi.org/10.1371/journ al.pone.02007 78
SCCS (2014) Opinion on the safety of aluminium in cosmetic prod-
ucts. SCCS/1525/14. Scientific Committee on Consumer Safety.
http://ec.europ a.eu/healt h/sites /healt h/files /scien tific _commi ttees
/consu mer_safet y/docs/sccs_o_153.pdf. Accessed 12 Sept 2019
SCCS (2018) The notes of guidance for the testing of cosmetic ingre-
dients and their safety evaluation 10th. revision. SCCS/1602/18.
Scientific Committee on Consumer Safety. https ://ec.europ a.eu/
healt h/sites /healt h/files /scien tific _commi ttees /consu mer_safet y/
docs/sccs_o_224.pdf. Accessed 12 Sept 2019
SCHEER (2017) Final opinion on tolerable intake of aluminium with
regards to adapting the migration limits for aluminium in toys.
Scientific Committee on Health, Environmental and Emerging
Risks. https ://doi.org/10.2875/26421 1
Seidowsky A, Dupuis E, Drueke T, Dard S, Massy ZA, Canaud B
(2018) Intoxication aluminique en hémodialyse chronique. Un
diagnostic rarement évoqué de nos jours. Illustration par un cas
clinique et revue de la littérature. Néphrologie Thérapeutique
14(1):35–41. https ://doi.org/10.1016/j.nephr o.2017.04.002
Sirot V, Traore T, Guérin T etal (2018) French infant total diet study:
exposure to selected trace elements and associated health risks.
Food Chem Toxicol 120:625–633. https ://doi.org/10.1016/j.
fct.2018.07.062
VKM (2013) Risk assessment of the exposure to aluminium through
food and the use of cosmetic products in the Norwegian popula-
tion. (VKM Report 2013: 20). Norwegian Scientific Committee
for Food Safety. https ://vkm.no/downl oad/18.17508 3d415 c86c5
73b59 c179/15016 78206 406/a729a 67e65 .pdf. Accessed 12 Sept
2019
WHO (2007) Model list of essential medicines—15th list (March
2007). World Health Organization, Geneva
WHO (2012) Global Advisory Committee on Vaccine Safety, report
of meeting held 6–7 June 2012. In: World Health Organization.
http://www.who.int/vacci ne_safet y/commi ttee/repor ts/Jun_2012/
en/. Accessed 19 June 2019
WHO (2017) Model List of Essential Medicines—20th list (March
2017) (Amended August 2017). World Health Organization,
Geneva
Yokel RA, McNamara PJ (2001) Aluminium toxicokinetics: an updated
minireview. Pharmacol Toxicol 88(4):159–167. https ://doi.org/1
0.1111/j.1600-0773.2001.88040 1.x
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