Estimation of exposure from different sources
Aluminium content in foods
The main sources of dietary aluminium exposure are summarised 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 aluminium 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/kg, respectively. The high contents found in these food groups are mainly due to the pools “spices” or cocoa-containing 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 contribution results from instant tea beverages. Other relevant sources of exposure are mixed vegetable salads, tea beverages, 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 German 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. However, aluminium content was below the detection limit in the respective samples. In general, there is only a slight difference 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 specific consumption pattern.
The estimated aluminium intake through food in the German 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 consumers (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 Australia 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 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 aluminium 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 inclusion 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 aluminium 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 aluminium 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 toddlers conducted by the Austrian agency for health and food safety (AGES 2017).
The above-mentioned estimates for infants do not consider that alternatives for infant formulas (e.g. soy-based or hypoallergenic formula) may contain much higher aluminium contents. For example, Dabeka et al. (2011) found in an extensive study of 473 different infant formulas and substitutes in Canada on average about fourfold higher aluminium 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 aluminium contents if they are soy based.
EFSA (2008) also concluded that adapted infant formulas, 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 breastfed 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 lowest 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 additives, 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, packaging, cooking, eating and storage of food can release aluminium 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 consumption of food from aluminium menu trays (average consumers: 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). Significant transition of aluminium into food is to be expected above all when uncoated aluminium articles are used in connection with acidic, basic or salty foodstuffs. In this context, the BfR had reported high aluminium contents in lye biscuits (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 aluminium or were produced by aluminium salt precipitation (“aluminium lakes”). Liu et al. (2013) analysed the aluminium 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” determined 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 exposure 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 dermal 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 aluminium 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 exposure dose of 0.27 mg Al/kg bw/week.
Aluminium intake through toothpaste
In toothpaste, the use of aluminium fluoride up to a concentration of 1500 ppm (0.15% based on the fluoride content) is permitted according to the European Cosmetics Regulation (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 Norwegian 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 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 antiperspirants 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 samples 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 content 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 remaining samples was 0.1%, with a maximum content of 0.8%. According to SCCS (2018) and RIVM (2006), a daily application of 18 g of sunscreen is assumed on 25 days/year. For the average aluminium content of 0.1%, an exposure equivalent 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 gastric 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 tolerable 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 aluminium hydroxide in tablet form or 320 mg (per 5 ml) in gel form. This would correspond to 173 mg or 111 mg aluminium 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 aluminium 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/alumina, carbohydrate compounds or fatty acid salts. Insoluble minerals, glass and clay/alumina are added to cosmetic products 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 available on the aluminium content in toys. According to investigations 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 aluminium 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 the current migration limits in Directive 2009/48/EC by approx. 60% (https://eur-lex.europa.eu/legal-content/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 different age groups
The relevant exposure contributions for different age groups are summed up below (Tables 7, 8). To calculate exposure 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 maximum 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 contributions from FCM. For highly exposed infants and toddlers, the maximum exposure is 1.4 mg/kg bw/week when vaccination 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 exposure is significantly lower and does not differ much between the different age groups.
For not occupationally exposed adults, the MAK Commission 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).
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).