Migration of aluminum from food contact materials to food—a health risk for consumers? Part I of III: exposure to aluminum, release of aluminum, tolerable weekly intake (TWI), toxicological effects of aluminum, study design, and methods

Background In spite of the prevalence of aluminum in nature, no organism has been found to date which requires this element for its biological functions. The possible health risks to human beings resulting from uptake of aluminum include detrimental effects to the hemopoietic system, the nervous system and bones. Aluminum is used in many fields and occurs in numerous foodstuffs. Food contact materials containing aluminum represent an anthropogenic source of dietary aluminum. Results As a result of their frequent use in private households a study was undertaken to detect migration of this metal to foodstuffs from drink containers, coffee pots, grill pans, and camping cookware made of aluminum. Conclusions An estimate of the health risk to consumers is calculated, based on the tolerable weekly intake (TWI) specified by the European Food Safety Authority of 1 mg/kg body weight for all groups of people. In some instances the TWI is significantly exceeded, dependent upon the food contact material and the food itself.


Background
Aluminum is the third most prevalent element in the earth's crust with a proportion of 7.5%. Certain metals such as iron and magnesium are essential for the human organism and maintenance of bodily functions and must be taken up through nourishment. Aluminum, on the other hand is, in spite of its prevalence, not known to have any function in human or animal organisms [1][2][3][4]. According to an older study, aluminum is also not essential for any higher plants [5]. 1 The main source of aluminum in the human body is food. Dermal uptake, on the other hand, plays a secondary role, in spite of the fact that deodorants containing aluminum have been repeatedly suggested to be related to an increase in risk of breast cancer [8][9][10]. Uptake through inhalation is negligible for the general public, although workers who breathe dust containing aluminum over an extended period have an increased tendency to contract pulmonary aluminosis (restrictive lung disease) [11]. Elemental aluminum finds a myriad of uses due to its excellent material properties such as castability in any shape, plasticity, heat conduction, low density, low melting point, oxidative passivation, and suppleness with concurrent toughness. Consequently, it is highly prized as a construction material, in electrotechnical applications, as packing material or as fuel for solid-fuel rockets, to name but a few uses. Aluminum compounds are used as food additives, in cosmetics and as or in pharmaceuticals. In addition, aluminum occurs naturally in foodstuffs [12][13][14][15][16]. Human exposure is divided into two categories, "external contact" and "dietary contact"; examples of these two categories are presented in Table 1.
Total human exposure to aluminum is for the most part the result of uptake from foodstuffs and food additives as well as migration from food contact materials [3].

Aluminum in foodstuffs
Aluminum occurs naturally in drinking water and in unprocessed foods [12,15,[17][18][19][20]. This natural proportion is also referred to as the "primary content, " and represents the unavoidable aluminum content in foods [16]. Aluminum occurs in foods of both plant and animal origin. The aluminum in plants reflects the content in the soil and in the water resulting from carryover. Certain plants take up more aluminum than others. Examples of plants that preferentially take up aluminum are tea bushes, leafy vegetables, and certain subtropical fruits [14] as well as spice plants [13]. In particular, plants that grow in acidic soil accumulate larger amounts of aluminum. The naturally occurring aluminum concentration in foodstuffs of animal origin is an indication of the aluminum content of the animal feed and the capability of the organs and tissues to accumulate aluminum [14,21]. Aluminum may find its way into processed foods through food additives as well as through migration from food contact materials that contain aluminum [22]. Table 2 presents typical aluminum concentration levels in foodstuffs of vegetable and animal origin.
It is shown in Table 2 that animal products such as milk products, sausage, or seafood as well as vegetables and baked goods exhibit concentrations of aluminum between 5.00 and 10.00 mg/kg and foodstuffs such as coffee, tea, spices, and herbs are found to have concentrations >10 mg/kg. Concentrations of aluminum in numerous foodstuffs have been determined in the Hessian State Laboratory in previous years and were published in part in the year 2011 [16].
In Table 3 these data are presented, expanded to included results obtained since 2011: As shown in Table 3, the values determined from Table 2 are confirmed by these results. Meat and other animal products such as milk products contain lower concentrations of aluminum than e.g., pine nuts, cocoa powder, chocolate, or bread, including baking mixes.

Aluminum in or resulting from food additives
Food additives containing aluminum belong to the secondary or anthropogenic sources and may have a decisive influence on the total aluminum concentration in foodstuffs. Various aluminum compounds are approved as additives in the European Union. Elemental aluminum may be used as a colorant. In addition, various additives containing aluminum are allowed for technical use. These include firming agents, releasing agents, and raising agents. The regulation (EC) No. 1333/2008 harmonizes the use of food additives in the European Union. The approved additives and their maximum amounts or maximum concentrations are listed in appendices II and III of the regulation.  Considering that aluminum containing food additives may contribute to an increase in the total dietary uptake of aluminum [22], the permissible maximum amounts in these regulations are comparatively high. Table 4 presents a summary of the various forms in which aluminum and aluminum compounds are used as food additives.

Aluminum from food contact materials
Aluminum and aluminum alloys are commonly used in the manufacture of utensils that come into contact with food. Along with food additives, these objects represent an additional anthropogenic source of aluminum in food. Before the end of the nineteenth century articles made of aluminum were considered luxury goods; however, with reductions in the cost of production, the scope of application was greatly expanded. Due to the material properties mentioned above, eating and drinking utensils as well as pots and pans have been manufactured out of aluminum since the end of the 1900s. The first widespread application was in the military, for use as eating utensils, pots, and canteens. New procedures for preparation, storage, and packaging of foodstuffs led to increased usage of aluminum in food products. Today, it is impossible to imagine the food sector without aluminum. Table 5 presents a summary of the various uses of aluminum in the field of food contact materials.

Specific release limit (SRL)
In September of 2013, the Council of Europe passed a resolution for metals and alloys that come into contact with foodstuffs [23]. In this resolution, specific release limits (SRL) for metals and alloys, including aluminum, were proposed. As a basic principle, the release of metal should remain ' As Low As Reasonably Achievable (ALARA). ' An SRL specifies, the maximal amount of metal ions (in mg) may be transferred from a defined surface of the contact material to the food (in kg) or food simulant. Known toxicological aspects of the given metals are taken into account. The SRL for the release of aluminum to foodstuffs was specified to be 5.00 mg/kg foodstuff [23]. Data from monitoring programs for foods and food simulants by the food industry as well as from members of the Europe Community show that this value can be adhered to [23]. The SRL is also used by official control authorities. In the studies presented in this paper, consumable liquids were also tested, whereby the SRL for liquids will be presented in the unit mg/L.

Tolerable weekly intake (TWI)
The Joint FAO/WHO Expert Committee on Food Additives (JECFA) and the Scientific Committee for Food (SCF) published a provisional tolerable weekly intake (PTWI) for aluminum of 7.00 mg/kg body weight (BW) per week. This value was derived from animal experiments studying the toxicology of aluminum in dogs, rats, and mice [24]. According to this, it would be permissible for an adult human weighing 70 kg to take up 490 mg per week and for a child weighing 15 kg an amount of 105 mg per week. More recent animal studies [25] suggest that damage may occur at lower dosages than 7.0 mg/kg per week so that in 2006 the provisional TWI was consequently reduced to 1.0 mg/kg BW. The European Food Safety Authority (EFSA) also specified a TWI for aluminum of 1.00 mg/kg BW per week, based on combined

Toxicological effects of aluminum
Uptake of aluminum can result in risks to human health. Aluminum has an effect on numerous biological processes in the body. The exact mechanism of aluminum toxicity is, however, not fully understood. It is considered certain that aluminum is potentially cell-and neurotoxic. [22]. Enzyme activity may be disrupted and mitochondrial function may be impaired. Aluminum may also produce oxidative stress [4]. In particular, three organ systems may be negatively affected by aluminum: the hemopoietic system, the nervous system and bones. It has also been suggested that aluminum may play a role in the occurrence of diseases such as breast cancer and Alzheimer's dementia [22]. The only direct connections that have been shown between aluminum and disease are for hemodialysis encephalopathy, osteomalacia (softening of the bones), anemia, and aluminosis (pathological changes to the lungs) [22,28]. Of particular importance are aluminum poisoning in the form of encephalopathy and osteomalacia. These effects may occur in patients with chronic kidney disease who are dependent upon dialysis or ingest phosphate binders containing aluminum for extended periods of time [29]. Dialysis encephalopathy 2 has been brought into connection with increased aluminum concentrations in the brain of dialysis patients. In order to adequately remove phosphate from the blood, the dialysis fluid contains an aluminum compound. The aluminum can then apparently accumulate in the body and in the brain. Patients may suffer from speech difficulties and muscle cramps brought on especially by trivalent aluminum ions, personality changes, accelerated dementia, and depressive moods [30,31]. The skeletal system has also been suggested as a potential target of aluminum toxicity [28]. Long-term uptake of comparatively large amounts of aluminum, e.g., taking antacids 3 containing aluminum, may cause an imbalance in the calcium and phosphate household with resultant softening of the bones [32]. Substantial aluminum contamination may result in delayed bone development [31] and development of anemia. Aluminum-induced anemia is typically macrocytic and hypochromatic, 4 often occurring in dialysis patients. The exact cause of this phenomenon remains unknown [31]. Aluminosis, also referred to as "aluminum lung" is an occupational disease of workers exposed to aluminum and aluminum oxide dust and vapors. Of all aluminum-related health risks, aluminosis has been known the longest. [29]. Aluminum compounds accumulate in the lungs and impair the self-cleaning system of the lungs. In addition, they may elicit inflammatory processes that induce irreversible tissue damage to the respiratory system and the lungs, possibly resulting in fibrosis [33,34]. Due to inadequate and disputable data, the involvement of aluminum in breast cancer and the development of Alzheimer's disease as mentioned in the discussion can neither be explicitly substantiated or negated. Indications of a relationship between aluminum and breast cancer result from observations that breast tissue of women with tumors to some extent may exhibit higher aluminum concentrations than tissue from healthy women. It should also be noted that the disproportionate 2 Encephalopathies are functional disorders of the central nervous system [30]. 3 Gastric acid binding pharmaceuticals. 4 Microcytic: undersized erythrocytes; hypochrome: erythrocytes are pale (hemoglobin deficiency).  [35]. Aside from the improved diagnostic methods for cancer of the breast, the use of antitranspirants or deodorants containing aluminum may also play a role. Since these substances are applied very close to the breast tissue, they could be involved in the development of breast cancer [9]. It must be noted, however, that the data related to this are contradictory and as a consequence it is not possible to draw scientifically tenable conclusions regarding antitranspirants or deodorants containing aluminum and breast cancer. As a reaction to this controversial situation, however, aluminum-free antitranspirants have begun to appear in the market. Alzheimer's disease is an illness characterized by disorders in cognitive areas such as memory and orientation disturbances [36]. Reports have been made of increased aluminum concentrations in certain areas of the brain [37]. As with the role that aluminum may play in the development of breast cancer, the role of aluminum in Alzheimer's disease remains very controversial. As possible mechanism, the neurotoxic potential of aluminum and the possibility that aluminum bound to transferrin may enter the brain have been suggested. There is no evidence that aluminum may be a singular causative factor for Alzheimer's disease, but may act as a co-factor that can abet the development of the disease [22].

Basis for the study
As a result of the importance of dietary aluminum exposure (see "Aluminum in or resulting from food additives" above) and the common use of aluminum food contact materials (see "Aluminum from food contact materials" above), in particular in private households, the migration of aluminum from contact materials to food was examined. This study was deemed necessary because of the incomplete data on migration of aluminum from household and cooking utensils within the framework of consumer protection and to this extent aluminum drinking bottles and aluminum stove-top moka pots (Part II) as well as aluminum grill pans and camping utensils (Part III) were examined for migration of aluminum to food.

Methods
To study the migration of aluminum from food contact materials to foodstuffs, various foods and food simulants were examined for their aluminum levels after storage or preparation in food contact materials containing aluminum by means of inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectroscopy (ICP-OES).

Samples
A total of 297 samples including food with and without contact to aluminum based cans, bottles, pans, or pots were analyzed. Water for all measurements was tap water from the local supplier (Wasserversorgungsbetriebe Wiesbaden, Germany) according to the guidelines on testing conditions for articles in contact with foodstuffs from the European Commission [38]. The water was stored in polyethylene (PE) canisters at 8 °C in a cold room for 1 week to insure that the same water was used throughout for testing. The naturally occurring background concentration of aluminum in the tap water was 0.7 µg/L, which was negligible compared to the test results (lowest concentration after migration was 10 µg/L), and was subtracted from all measurements of samples prepared with tap water. Powder samples were shaken with water in order to avoid segregation effects. and high-purity acids. Rhodium was used as internal standard for ICP-MS measurements. The limit of quantification (LOQ) depended on initial weight as well as on the measurement system (listed in Table 6. Quality assurance was performed by the use of standard reference materials (TM-15.2 water (33.9 ± 4.6 µg/L), rice flour (4.21 ± 0.34 mg/kg), apple leaves (286 ± 9 mg/kg), and blanks, which were also digested and treated the same as the samples. The reference materials were dissolved and analyzed in triplicate, whereby according to our internal specification for quality control, the recovery rate for aluminum had to be between 90 and 110%. In regard to blank values: The chemical blank values (n = 3) were found to be 0.005 ± 0.002 mg/kg and are therefore negligible in regard to aluminum concentration in the samples tested. With regard to the drinking bottles and moka pots please see Part II (Migration of aluminum to food from drinking bottles and moka pots) and for camping articles Part III (Migration of aluminum to food from aluminum bowls and camping utensils).

Results, discussion, conclusions
All results of this study are presented in Part II (Migration of aluminum to food from drinking bottles and moka pots) and for camping articles Part III (Migration of aluminum to food from camping dishes and utensils made of aluminum).